Tesamorelin

1. Studied for

   All the randomized trials pooled together

   A systematic review and random-effects meta-analysis searching PubMed, Embase, Scopus, Web of Science and CENTRAL through July 2025 identified 5 randomized controlled trials of tesamorelin against placebo in adults with HIV. Pooled results showed reductions in visceral fat (mean difference -27.71 cm2, 95% CI -38.37 to -17.06; P<0.001), trunk fat (-1.18 kg, 95% CI -1.40 to -0.96; P<0.001), limb fat (-0.22 kg, 95% CI -0.35 to -0.08; P=0.001), liver fat percentage (-4.28%, 95% CI -6.31 to -2.24; P<0.001) and waist circumference (-1.61 cm, 95% CI -2.28 to -0.95; P<0.001), and an increase in lean body mass (+1.42 kg, 95% CI 1.13 to 1.71; P<0.001). No significant reduction in the fat under the skin and no significant BMI change were found, and there was no significant change in CD4+ T-cell counts. Adverse events reported across the pooled trials include joint pain, muscle pain, pins and needles, and application-site reactions such as redness. The authors' own conclusion states the improvements occurred without serious side effects or perturbation of glucose; that is their summary of their pooled set, and this page does not adopt it as a safety statement of its own. meta-analysis of 5 human randomized controlled trials Preclinical strong Convergent results from more than one randomized controlled trial in people, or a meta-analysis pooling them. The design is the highest available. The ceiling is the population: every controlled fat trial behind a 'strong' rating on this page ran in adults living with HIV who had excess abdominal fat, so 'strong' means strong inside that population and establishes nothing outside it. Open for the full finding and the paper it came from.

   In the literature

   All the randomized trials pooled together

   A systematic review and random-effects meta-analysis searching PubMed, Embase, Scopus, Web of Science and CENTRAL through July 2025 identified 5 randomized controlled trials of tesamorelin against placebo in adults with HIV. Pooled results showed reductions in visceral fat (mean difference -27.71 cm2, 95% CI -38.37 to -17.06; P<0.001), trunk fat (-1.18 kg, 95% CI -1.40 to -0.96; P<0.001), limb fat (-0.22 kg, 95% CI -0.35 to -0.08; P=0.001), liver fat percentage (-4.28%, 95% CI -6.31 to -2.24; P<0.001) and waist circumference (-1.61 cm, 95% CI -2.28 to -0.95; P<0.001), and an increase in lean body mass (+1.42 kg, 95% CI 1.13 to 1.71; P<0.001). No significant reduction in the fat under the skin and no significant BMI change were found, and there was no significant change in CD4+ T-cell counts. Adverse events reported across the pooled trials include joint pain, muscle pain, pins and needles, and application-site reactions such as redness. The authors' own conclusion states the improvements occurred without serious side effects or perturbation of glucose; that is their summary of their pooled set, and this page does not adopt it as a safety statement of its own.^{References 1}

   Modelmeta-analysis of 5 human randomized controlled trials

   Confidence: strong

   Convergent results from more than one randomized controlled trial in people, or a meta-analysis pooling them. The design is the highest available. The ceiling is the population: every controlled fat trial behind a 'strong' rating on this page ran in adults living with HIV who had excess abdominal fat, so 'strong' means strong inside that population and establishes nothing outside it.

   Source

   Badran AS, Helal A, Shata KS, Ayesh H. Body composition, hepatic fat, metabolic, and safety outcomes of tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: a meta-analysis of randomized controlled trials. Obes Res Clin Pract. 2026;20(1):2-12. doi:10.1016/j.orcp.2026.01.002 (PMID 41545261)

   PubMed 41545261

   How this citation was checked

   Re-resolved live in the source pass, and deliberately so: a recent citation is exactly where a fabrication would hide. PubMed esummary and efetch on PMID 41545261 returned Obes Res Clin Pract 2026 Jan-Feb;20(1):2-12, full author list Badran AS, Helal A, Shata KS, Ayesh H, DOI 10.1016/j.orcp.2026.01.002, and an abstract carrying all 6 pooled effect sizes verbatim. Crossref on the DOI independently returned Obesity Research and Clinical Practice, volume 20, issue 1, pages 2-12, issued 2026-01, first author Badran Ahmed Samy. The abstract's adverse-event list is arthralgia, myalgia, paresthesia and application-site reactions like erythema, rendered in plain words above; peripheral edema does not appear in it and is not attributed here.

2. Studied for

   Pooled analysis of both phase 3 trials, including fat under the skin and 52-week durability

   Pooling 2 multicenter phase 3 trials that randomized 806 participants already receiving antiretroviral drugs 2:1 to tesamorelin (n=543) or placebo (n=263), deep visceral fat fell by 24 plus or minus 41 cm2 at week 26 against a rise of 2 plus or minus 35 cm2 on placebo (P<0.001; between-group effect -15.4%), while the fat just under the skin of the abdomen did not significantly change (-2 plus or minus 32 against 2 plus or minus 29 cm2, P=0.08; between-group effect -0.6%). Triglycerides fell 37 plus or minus 139 against a 6 plus or minus 112 mg/dL rise (P<0.001) and mean IGF-I rose 108 plus or minus 112 against -7 plus or minus 64 ng/mL (P<0.001). In the group that continued to week 52, the reductions in visceral fat (-35 plus or minus 50 cm2, or -17.5 plus or minus 23.3%) and waist circumference (-3.4 plus or minus 6.0 cm) held. The authors reported no clinically meaningful between-group differences in glucose parameters at weeks 26 and 52. The selectivity is the point here: the deep depot moved and the depot under the skin did not. pooled analysis of 2 human multicenter randomized double-blind placebo-controlled phase 3 trials (n=806, 26 weeks plus a 26-week extension) Preclinical strong Convergent results from more than one randomized controlled trial in people, or a meta-analysis pooling them. The design is the highest available. The ceiling is the population: every controlled fat trial behind a 'strong' rating on this page ran in adults living with HIV who had excess abdominal fat, so 'strong' means strong inside that population and establishes nothing outside it. Open for the full finding and the paper it came from.

   In the literature

   Pooled analysis of both phase 3 trials, including fat under the skin and 52-week durability

   Pooling 2 multicenter phase 3 trials that randomized 806 participants already receiving antiretroviral drugs 2:1 to tesamorelin (n=543) or placebo (n=263), deep visceral fat fell by 24 plus or minus 41 cm2 at week 26 against a rise of 2 plus or minus 35 cm2 on placebo (P<0.001; between-group effect -15.4%), while the fat just under the skin of the abdomen did not significantly change (-2 plus or minus 32 against 2 plus or minus 29 cm2, P=0.08; between-group effect -0.6%). Triglycerides fell 37 plus or minus 139 against a 6 plus or minus 112 mg/dL rise (P<0.001) and mean IGF-I rose 108 plus or minus 112 against -7 plus or minus 64 ng/mL (P<0.001). In the group that continued to week 52, the reductions in visceral fat (-35 plus or minus 50 cm2, or -17.5 plus or minus 23.3%) and waist circumference (-3.4 plus or minus 6.0 cm) held. The authors reported no clinically meaningful between-group differences in glucose parameters at weeks 26 and 52. The selectivity is the point here: the deep depot moved and the depot under the skin did not.^{References 2}

   Modelpooled analysis of 2 human multicenter randomized double-blind placebo-controlled phase 3 trials (n=806, 26 weeks plus a 26-week extension)

   Confidence: strong

   Convergent results from more than one randomized controlled trial in people, or a meta-analysis pooling them. The design is the highest available. The ceiling is the population: every controlled fat trial behind a 'strong' rating on this page ran in adults living with HIV who had excess abdominal fat, so 'strong' means strong inside that population and establishes nothing outside it.

   Source

   Falutz J, Mamputu JC, Potvin D, et al. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. 2010;95(9):4291-4304. doi:10.1210/jc.2010-0490 (PMID 20554713)

   PubMed 20554713

   How this citation was checked

   Re-resolved live in the source pass against 2 independent registries. PubMed efetch on PMID 20554713 returned J Clin Endocrinol Metab 2010 Sep;95(9):4291-304, first author Falutz J, DOI 10.1210/jc.2010-0490, and the full abstract from which every figure above was transcribed. Crossref on the DOI independently returned The Journal of Clinical Endocrinology and Metabolism, volume 95, issue 9, pages 4291-4304, issued 2010-09, first author Falutz Julian.

3. Studied for

   Pivotal phase 3 trial of deep abdominal fat, in adults with HIV

   In a 26-week randomized, double-blind, placebo-controlled trial in 412 adults with HIV and abdominal fat accumulation, the deep fat around the organs, measured by CT scan, went down by 15.2% in the tesamorelin group and up by 5.0% in the placebo group. Triglycerides fell by 50 mg/dL against a rise of 9 mg/dL, the total-cholesterol-to-HDL ratio fell by 0.31 against a rise of 0.21, and IGF-I rose by 81.0% against a 5.0% fall (P<0.001 for all of these). The investigators reported no significant differences in blood-sugar measures, and reported that adverse events did not differ significantly between groups although more people in the tesamorelin group withdrew because of an adverse event. This is a research outcome in a single specific study population and is not a general body-composition claim. human randomized double-blind placebo-controlled trial (n=412, 26 weeks) Preclinical strong Convergent results from more than one randomized controlled trial in people, or a meta-analysis pooling them. The design is the highest available. The ceiling is the population: every controlled fat trial behind a 'strong' rating on this page ran in adults living with HIV who had excess abdominal fat, so 'strong' means strong inside that population and establishes nothing outside it. Open for the full finding and the paper it came from.

   In the literature

   Pivotal phase 3 trial of deep abdominal fat, in adults with HIV

   In a 26-week randomized, double-blind, placebo-controlled trial in 412 adults with HIV and abdominal fat accumulation, the deep fat around the organs, measured by CT scan, went down by 15.2% in the tesamorelin group and up by 5.0% in the placebo group. Triglycerides fell by 50 mg/dL against a rise of 9 mg/dL, the total-cholesterol-to-HDL ratio fell by 0.31 against a rise of 0.21, and IGF-I rose by 81.0% against a 5.0% fall (P<0.001 for all of these). The investigators reported no significant differences in blood-sugar measures, and reported that adverse events did not differ significantly between groups although more people in the tesamorelin group withdrew because of an adverse event. This is a research outcome in a single specific study population and is not a general body-composition claim.^{References 3}

   Modelhuman randomized double-blind placebo-controlled trial (n=412, 26 weeks)

   Confidence: strong

   Convergent results from more than one randomized controlled trial in people, or a meta-analysis pooling them. The design is the highest available. The ceiling is the population: every controlled fat trial behind a 'strong' rating on this page ran in adults living with HIV who had excess abdominal fat, so 'strong' means strong inside that population and establishes nothing outside it.

   Source

   Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359-2370. doi:10.1056/NEJMoa072375 (PMID 18057338)

   PubMed 18057338

   How this citation was checked

   Re-resolved live in the source pass. PubMed E-utilities esummary and efetch on PMID 18057338 returned N Engl J Med 2007 Dec 6;357(23):2359-70, first author Falutz J, DOI 10.1056/NEJMoa072375, title matching. Crossref on the same DOI independently returned New England Journal of Medicine, volume 357, issue 23, pages 2359-2370, issued 2007-12-06, first author Falutz Julian. Every figure above was read from the retrieved abstract text: VAT -15.2% against +5.0%, triglycerides -50 against +9 mg per deciliter, TC:HDL -0.31 against +0.21, IGF-I +81.0% against -5.0%, P<0.001 for all comparisons, plus the verbatim 'No significant differences were observed in glycemic measures' and the withdrawal statement.

4. Studied for

   What happens when exposure stops

   In a 26-week extension of a phase 3 trial, 410 participants had been randomized to tesamorelin (n=273) or placebo (n=137) for the first 26 weeks. At week 26 the people originally on tesamorelin were re-randomized to continue or to switch to placebo, while the people originally on placebo were switched onto tesamorelin. Among those who kept taking it, the reduction in visceral fat held at -18% across 52 weeks (P<0.001 against baseline), as did the triglyceride change (-51 mg/dL, P<0.001 against baseline). The authors reported that upon discontinuation, visceral fat reaccumulated, and concluded that the effects on visceral fat do not last beyond the period of exposure. Changes in glucose parameters over 52 weeks were described as not clinically significant. human randomized double-blind trial with a 26-week extension (n=410 randomized, 52 weeks total) Preclinical strong Convergent results from more than one randomized controlled trial in people, or a meta-analysis pooling them. The design is the highest available. The ceiling is the population: every controlled fat trial behind a 'strong' rating on this page ran in adults living with HIV who had excess abdominal fat, so 'strong' means strong inside that population and establishes nothing outside it. Open for the full finding and the paper it came from.

   In the literature

   What happens when exposure stops

   In a 26-week extension of a phase 3 trial, 410 participants had been randomized to tesamorelin (n=273) or placebo (n=137) for the first 26 weeks. At week 26 the people originally on tesamorelin were re-randomized to continue or to switch to placebo, while the people originally on placebo were switched onto tesamorelin. Among those who kept taking it, the reduction in visceral fat held at -18% across 52 weeks (P<0.001 against baseline), as did the triglyceride change (-51 mg/dL, P<0.001 against baseline). The authors reported that upon discontinuation, visceral fat reaccumulated, and concluded that the effects on visceral fat do not last beyond the period of exposure. Changes in glucose parameters over 52 weeks were described as not clinically significant.^{References 4}

   Modelhuman randomized double-blind trial with a 26-week extension (n=410 randomized, 52 weeks total)

   Confidence: strong

   Convergent results from more than one randomized controlled trial in people, or a meta-analysis pooling them. The design is the highest available. The ceiling is the population: every controlled fat trial behind a 'strong' rating on this page ran in adults living with HIV who had excess abdominal fat, so 'strong' means strong inside that population and establishes nothing outside it.

   Source

   Falutz J, Allas S, Mamputu JC, et al. Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation. AIDS. 2008;22(14):1719-1728. doi:10.1097/QAD.0b013e32830a5058 (PMID 18690162)

   PubMed 18690162

   How this citation was checked

   Re-resolved live in the source pass. PubMed efetch on PMID 18690162 returned AIDS 2008 Sep 12;22(14):1719-28, first author Falutz J, DOI 10.1097/QAD.0b013e32830a5058. Crossref on the DOI independently returned AIDS, volume 22, issue 14, pages 1719-1728, issued 2008-09-12, first author Falutz Julian. The retrieved abstract supplied -18% at 52 weeks, -51 mg/dl triglycerides, and the 2 sentences this entry's closing clause paraphrases, one of which reads 'Upon discontinuation of tesamorelin, VAT reaccumulated'. The abstract also states that only the tesamorelin arm was rerandomized (T-T n=154, T-P n=50) and that people originally on placebo were switched onto tesamorelin (P-T n=111), which is why an earlier draft's claim that both arms were re-randomized was corrected.

5. Studied for

   Second phase 3 trial with a blinded withdrawal arm

   In a 12-month, two-phase study of 404 adults with HIV and excess abdominal fat, deep visceral fat fell 10.9% (21 cm2) on tesamorelin against 0.6% (1 cm2) on placebo during the 6-month efficacy phase (P<0.0001), with improvements in trunk fat (P<0.001), waist circumference (P=0.02) and waist-to-hip ratio (P=0.001), and no change in limb fat or in the abdominal fat just under the skin. IGF-1 rose (P<0.001) but no change in glucose parameters was seen. Visceral fat was reduced by approximately 18% (P<0.001) in the participants who continued for 12 months, and the investigators reported that the initial 6-month improvements were rapidly lost in those switched from tesamorelin to placebo. human randomized double-blind placebo-controlled trial with blinded re-randomization (n=404, 12 months) Preclinical strong Convergent results from more than one randomized controlled trial in people, or a meta-analysis pooling them. The design is the highest available. The ceiling is the population: every controlled fat trial behind a 'strong' rating on this page ran in adults living with HIV who had excess abdominal fat, so 'strong' means strong inside that population and establishes nothing outside it. Open for the full finding and the paper it came from.

   In the literature

   Second phase 3 trial with a blinded withdrawal arm

   In a 12-month, two-phase study of 404 adults with HIV and excess abdominal fat, deep visceral fat fell 10.9% (21 cm2) on tesamorelin against 0.6% (1 cm2) on placebo during the 6-month efficacy phase (P<0.0001), with improvements in trunk fat (P<0.001), waist circumference (P=0.02) and waist-to-hip ratio (P=0.001), and no change in limb fat or in the abdominal fat just under the skin. IGF-1 rose (P<0.001) but no change in glucose parameters was seen. Visceral fat was reduced by approximately 18% (P<0.001) in the participants who continued for 12 months, and the investigators reported that the initial 6-month improvements were rapidly lost in those switched from tesamorelin to placebo.^{References 5}

   Modelhuman randomized double-blind placebo-controlled trial with blinded re-randomization (n=404, 12 months)

   Confidence: strong

   Convergent results from more than one randomized controlled trial in people, or a meta-analysis pooling them. The design is the highest available. The ceiling is the population: every controlled fat trial behind a 'strong' rating on this page ran in adults living with HIV who had excess abdominal fat, so 'strong' means strong inside that population and establishes nothing outside it.

   Source

   Falutz J, Potvin D, Mamputu JC, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension. J Acquir Immune Defic Syndr. 2010;53(3):311-322. doi:10.1097/QAI.0b013e3181cbdaff (PMID 20101189)

   PubMed 20101189

   How this citation was checked

   Re-resolved live in the source pass. PubMed efetch on PMID 20101189 returned J Acquir Immune Defic Syndr 2010 Mar;53(3):311-22, first author Falutz J, DOI 10.1097/QAI.0b013e3181cbdaff, with the abstract supplying every figure above verbatim. Crossref on the DOI independently returned JAIDS Journal of Acquired Immune Deficiency Syndromes, volume 53, issue 3, pages 311-322, issued 2010-03-01, first author Falutz Julian.

6. Studied for

   Inflammation and clotting markers in the blood

   In 410 adults with HIV and abdominal adiposity randomized to tesamorelin (n=273) or placebo (n=137) for 26 weeks, exposure produced a significant decrease from baseline in tissue plasminogen activator antigen (-2.2 plus or minus 2.5 against -1.6 plus or minus 2.9 ng/mL, P<0.05), while changes in plasminogen activator inhibitor-1 antigen were NOT significant against placebo. Among the participants receiving tesamorelin, changes in these markers were associated with the change in visceral fat (PAI-1 antigen rho=0.16, P=0.02; tPA antigen rho=0.16, P=0.02; adiponectin rho=-0.27, P<0.001), and those associations held after controlling for the IGF-1 change. The authors describe the effect as modest and call for further studies to determine clinical significance. These are biomarker observations, not demonstrated clinical anti-inflammatory outcomes. human randomized placebo-controlled trial, biomarker analysis (n=410, 26 weeks) Preclinical moderate A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product. Open for the full finding and the paper it came from.

   In the literature

   Inflammation and clotting markers in the blood

   In 410 adults with HIV and abdominal adiposity randomized to tesamorelin (n=273) or placebo (n=137) for 26 weeks, exposure produced a significant decrease from baseline in tissue plasminogen activator antigen (-2.2 plus or minus 2.5 against -1.6 plus or minus 2.9 ng/mL, P<0.05), while changes in plasminogen activator inhibitor-1 antigen were NOT significant against placebo. Among the participants receiving tesamorelin, changes in these markers were associated with the change in visceral fat (PAI-1 antigen rho=0.16, P=0.02; tPA antigen rho=0.16, P=0.02; adiponectin rho=-0.27, P<0.001), and those associations held after controlling for the IGF-1 change. The authors describe the effect as modest and call for further studies to determine clinical significance. These are biomarker observations, not demonstrated clinical anti-inflammatory outcomes.^{References 6}

   Modelhuman randomized placebo-controlled trial, biomarker analysis (n=410, 26 weeks)

   Confidence: moderate

   A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product.

   Source

   Stanley TL, Falutz J, Mamputu JC, Soulban G, Potvin D, Grinspoon SK. Effects of tesamorelin on inflammatory markers in HIV patients with excess abdominal fat: relationship with visceral adipose reduction. AIDS. 2011;25(10):1281-1288. doi:10.1097/QAD.0b013e328347f3f1 (PMID 21516030; PMC3673013)

   PubMed 21516030

   How this citation was checked

   Re-resolved live in the source pass. PubMed efetch on PMID 21516030 returned AIDS 2011 Jun 19;25(10):1281-8, author list Stanley TL, Falutz J, Mamputu JC, Soulban G, Potvin D, Grinspoon SK, DOI 10.1097/QAD.0b013e328347f3f1, PMCID PMC3673013. Crossref on the DOI independently returned AIDS, volume 25, issue 10, pages 1281-1288, issued 2011-06-19, first author Stanley Takara L. The abstract states that changes in PAI-1 antigen were not significant in the tesamorelin group compared to placebo, which is preserved above rather than smoothed over.

7. Studied for

   Cognition in older adults, with and without mild cognitive impairment

   In a 20-week randomized, double-blind, placebo-controlled trial, 152 adults aged 55 to 87 (66 of them with mild cognitive impairment) took daily subcutaneous tesamorelin or placebo themselves. The analysis of all randomized participants indicated a favorable effect on cognition (P=.03), comparable in the adults with mild cognitive impairment and in the healthy older adults, and the analysis restricted to completers showed the same pattern (P=.002). Follow-on analyses indicated a positive effect on executive function (P=.005), assessed with Stroop Color-Word Interference, Task Switching, the Self-Ordered Pointing Test and Word Fluency, and a non-significant trend in verbal memory (P=.08). IGF-1 rose by 117% (P<.001), staying within the physiological range, and percent body fat fell 7.4% (P<.001). The metabolic signal that cuts the other way is kept here: fasting insulin rose within the normal range by 35% in the adults with mild cognitive impairment (P<.001) but not in the healthy adults. Adverse events were mild and were reported by 68% of the adults receiving tesamorelin against 36% on placebo. This is a single trial in a research setting, it has not been replicated at scale, and it supports no cognitive-benefit claim. human randomized double-blind placebo-controlled trial (n=152 randomized, 137 completed, 20 weeks) Preclinical moderate A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product. Open for the full finding and the paper it came from.

   In the literature

   Cognition in older adults, with and without mild cognitive impairment

   In a 20-week randomized, double-blind, placebo-controlled trial, 152 adults aged 55 to 87 (66 of them with mild cognitive impairment) took daily subcutaneous tesamorelin or placebo themselves. The analysis of all randomized participants indicated a favorable effect on cognition (P=.03), comparable in the adults with mild cognitive impairment and in the healthy older adults, and the analysis restricted to completers showed the same pattern (P=.002). Follow-on analyses indicated a positive effect on executive function (P=.005), assessed with Stroop Color-Word Interference, Task Switching, the Self-Ordered Pointing Test and Word Fluency, and a non-significant trend in verbal memory (P=.08). IGF-1 rose by 117% (P<.001), staying within the physiological range, and percent body fat fell 7.4% (P<.001). The metabolic signal that cuts the other way is kept here: fasting insulin rose within the normal range by 35% in the adults with mild cognitive impairment (P<.001) but not in the healthy adults. Adverse events were mild and were reported by 68% of the adults receiving tesamorelin against 36% on placebo. This is a single trial in a research setting, it has not been replicated at scale, and it supports no cognitive-benefit claim.^{References 7}

   Modelhuman randomized double-blind placebo-controlled trial (n=152 randomized, 137 completed, 20 weeks)

   Confidence: moderate

   A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product.

   Source

   Baker LD, Barsness SM, Borson S, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. Arch Neurol. 2012;69(11):1420-1429. doi:10.1001/archneurol.2012.1970 (PMID 22869065; PMC3764914)

   PubMed 22869065

   How this citation was checked

   Re-resolved live in the source pass. PubMed esummary and efetch on PMID 22869065 returned Arch Neurol 2012 Nov;69(11):1420-9, first author Baker LD, DOI 10.1001/archneurol.2012.1970, PMCID PMC3764914. Crossref on the DOI independently returned Archives of Neurology, volume 69, issue 11, first page 1420, issued 2012-11-01, first author Baker Laura D. The retrieved abstract lists the executive-function battery exactly as written above with no Trail Making B anywhere in the record, contains no cerebrospinal fluid measurement of any kind, and describes participants only as having 'mild cognitive impairment (MCI)', so the 'amnestic' qualifier carried by an earlier draft was removed as unsourced. The abstract also supplied the fasting-insulin result, so this entry does not keep only the favorable numbers.

8. Studied for

   A second randomized cognition trial that did not confirm the signal

   A 6-month phase 2 randomized open-label trial compared daily subcutaneous tesamorelin against standard of care for neurocognitive impairment in 73 virally suppressed people with HIV and abdominal obesity, randomized 3:2. The tesamorelin group showed a trend toward improved neurocognitive performance at 6 months (mean change 0.146; 95% CI -0.002 to 0.294; P=.060) while the standard-of-care group did not (0.103; 95% CI -0.095 to 0.301; P=.295), but the difference between the groups was not significant (P=.673). IGF-1 rose, but the changes did not correlate with the summary change score or with waist circumference. Waist circumference fell more in the tesamorelin group (median difference -2.7 cm; P=.015). The authors noted insufficient power and the absence of a placebo arm and concluded that the study suggests no clear benefit. This null result is carried deliberately, as the counterweight to the single positive cognition trial above. human phase 2 randomized open-label trial against standard of care (n=73, 6 months) Preclinical moderate A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product. Open for the full finding and the paper it came from.

   In the literature

   A second randomized cognition trial that did not confirm the signal

   A 6-month phase 2 randomized open-label trial compared daily subcutaneous tesamorelin against standard of care for neurocognitive impairment in 73 virally suppressed people with HIV and abdominal obesity, randomized 3:2. The tesamorelin group showed a trend toward improved neurocognitive performance at 6 months (mean change 0.146; 95% CI -0.002 to 0.294; P=.060) while the standard-of-care group did not (0.103; 95% CI -0.095 to 0.301; P=.295), but the difference between the groups was not significant (P=.673). IGF-1 rose, but the changes did not correlate with the summary change score or with waist circumference. Waist circumference fell more in the tesamorelin group (median difference -2.7 cm; P=.015). The authors noted insufficient power and the absence of a placebo arm and concluded that the study suggests no clear benefit. This null result is carried deliberately, as the counterweight to the single positive cognition trial above.^{References 8}

   Modelhuman phase 2 randomized open-label trial against standard of care (n=73, 6 months)

   Confidence: moderate

   A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product.

   Source

   Ellis RJ, Vaida F, Hu K, et al. Effects of tesamorelin on neurocognitive impairment in persons with HIV and abdominal obesity. J Infect Dis. 2025;231(5):1230-1238. doi:10.1093/infdis/jiaf012 (PMID 39813152)

   PubMed 39813152

   How this citation was checked

   Re-resolved live in the source pass. PubMed efetch on PMID 39813152 returned J Infect Dis 2025 Jun 2;231(5):1230-1238, first author Ellis RJ, DOI 10.1093/infdis/jiaf012, and the abstract from which every figure above and the authors' own 'this study suggests no clear benefit' were transcribed. Crossref on the DOI independently returned The Journal of Infectious Diseases, volume 231, issue 5, pages 1230-1238, first author Ellis Ronald J.

9. Studied for

   Liver fat over 12 months, measured by magnetic resonance spectroscopy

   In a 12-month randomized, double-blind, multicenter trial, 61 people with HIV whose livers were at least 5% fat by magnetic resonance spectroscopy were assigned 1:1 to tesamorelin or an identical placebo. Liver fat fell further on tesamorelin, with an absolute effect size of -4.1% (95% CI -7.6 to -0.7; p=0.018), a -37% relative reduction from baseline (95% CI -67 to -7; p=0.016). After 12 months, 35% of the tesamorelin group against 4% of the placebo group had a liver fat fraction below 5%, the threshold used to define the condition (p=0.0069). Changes in fasting glucose and glycated hemoglobin were not different between groups at 12 months. People receiving tesamorelin reported more localized application-site complaints, none judged serious. The authors framed their conclusion as tesamorelin 'might be beneficial' and called for further study of long-term effects on liver tissue. Note the scope deliberately: this entry reports liver fat only. The abstract of this trial reports no fibrosis endpoint of any kind, and the fibrosis language that circulates around this trial traces to the introductions of the authors' own later papers rather than to this trial's reported endpoints. human randomized double-blind placebo-controlled multicenter trial (n=61, 12 months, followed by a 6-month open-label phase) Preclinical moderate A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product. Open for the full finding and the paper it came from.

   In the literature

   Liver fat over 12 months, measured by magnetic resonance spectroscopy

   In a 12-month randomized, double-blind, multicenter trial, 61 people with HIV whose livers were at least 5% fat by magnetic resonance spectroscopy were assigned 1:1 to tesamorelin or an identical placebo. Liver fat fell further on tesamorelin, with an absolute effect size of -4.1% (95% CI -7.6 to -0.7; p=0.018), a -37% relative reduction from baseline (95% CI -67 to -7; p=0.016). After 12 months, 35% of the tesamorelin group against 4% of the placebo group had a liver fat fraction below 5%, the threshold used to define the condition (p=0.0069). Changes in fasting glucose and glycated hemoglobin were not different between groups at 12 months. People receiving tesamorelin reported more localized application-site complaints, none judged serious. The authors framed their conclusion as tesamorelin 'might be beneficial' and called for further study of long-term effects on liver tissue. Note the scope deliberately: this entry reports liver fat only. The abstract of this trial reports no fibrosis endpoint of any kind, and the fibrosis language that circulates around this trial traces to the introductions of the authors' own later papers rather than to this trial's reported endpoints.^{References 9}

   Modelhuman randomized double-blind placebo-controlled multicenter trial (n=61, 12 months, followed by a 6-month open-label phase)

   Confidence: moderate

   A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product.

   Source

   Stanley TL, Fourman LT, Feldpausch MN, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019;6(12):e821-e830. doi:10.1016/S2352-3018(19)30338-8 (PMID 31611038; PMC6981288)

   PubMed 31611038

   How this citation was checked

   Re-resolved live in the source pass. PubMed esummary and efetch on PMID 31611038 returned Lancet HIV 2019 Dec;6(12):e821-e830, first author Stanley TL, DOI 10.1016/S2352-3018(19)30338-8, PMCID PMC6981288. Crossref on the DOI independently returned The Lancet HIV, volume 6, issue 12, pages e821-e830, issued 2019-12, first author Stanley Takara L. Every number above was transcribed from the retrieved abstract, including the -4.1% absolute and -37% relative effect sizes, the 35% against 4% resolution rates and the application-site sentence. The same retrieval confirmed that the abstract's reported endpoints are hepatic fat fraction only, which is why the area heading promises no result about scarring of the liver.

10. Studied for

    Blood sugar, measured over 12 weeks in adults who already have type 2 diabetes

    A 12-week randomized, placebo-controlled study of 53 adults with type 2 diabetes used 3 groups: placebo and 2 active arms at different exposure levels. The main outcome was the relative insulin response after drinking glucose. No significant differences were found between groups in that response over the 12 weeks, and at week 12 fasting glucose, HbA1c and overall glycemic control were not significantly different between groups. Relevant changes to diabetes medication were similar between groups and no participant left the study because of loss of glycemic control. Total cholesterol (-0.3 plus or minus 0.6 mmol/L) and non-HDL cholesterol (-0.3 plus or minus 0.5 mmol/L) fell significantly from baseline to week 12 in the higher-exposure arm (p<0.05 against placebo). This is small and short. The authors frame it as evidence that exposure did not alter insulin response or glycemic control over 12 weeks, not as proof of long-term metabolic neutrality, and neutrality is not an improvement. human randomized placebo-controlled three-arm study in type 2 diabetes (n=53, 12 weeks) Preclinical moderate A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product. Open for the full finding and the paper it came from.

    In the literature

    Blood sugar, measured over 12 weeks in adults who already have type 2 diabetes

    A 12-week randomized, placebo-controlled study of 53 adults with type 2 diabetes used 3 groups: placebo and 2 active arms at different exposure levels. The main outcome was the relative insulin response after drinking glucose. No significant differences were found between groups in that response over the 12 weeks, and at week 12 fasting glucose, HbA1c and overall glycemic control were not significantly different between groups. Relevant changes to diabetes medication were similar between groups and no participant left the study because of loss of glycemic control. Total cholesterol (-0.3 plus or minus 0.6 mmol/L) and non-HDL cholesterol (-0.3 plus or minus 0.5 mmol/L) fell significantly from baseline to week 12 in the higher-exposure arm (p<0.05 against placebo). This is small and short. The authors frame it as evidence that exposure did not alter insulin response or glycemic control over 12 weeks, not as proof of long-term metabolic neutrality, and neutrality is not an improvement.^{References 10}

    Modelhuman randomized placebo-controlled three-arm study in type 2 diabetes (n=53, 12 weeks)

    Confidence: moderate

    A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product.

    Source

    Clemmons DR, Miller S, Mamputu JC. Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: a randomized, placebo-controlled trial. PLoS One. 2017;12(6):e0179538. doi:10.1371/journal.pone.0179538 (PMID 28617838; PMC5472315)

    PubMed 28617838

    How this citation was checked

    Re-resolved live in the source pass. PubMed esummary and efetch on PMID 28617838 returned PLoS One 2017 Jun 15;12(6):e0179538, authors Clemmons DR, Miller S, Mamputu JC, DOI 10.1371/journal.pone.0179538, PMCID PMC5472315, and an abstract confirming n=53, 12 weeks, 3 arms, the null insulin-response result, the null week-12 comparisons, the no-discontinuation statement and both lipid figures. Crossref on the DOI independently returned PLOS ONE, volume 12, issue 6, page e0179538, issued 2017-06-15, first author Clemmons David R. An earlier draft's '5 US sites' and '4-week follow-up' details appear nowhere in the retrieved record and remain deleted.

11. Studied for

    Liver fat measured alongside deep abdominal fat

    In a 6-month double-blind randomized placebo-controlled trial of 50 adults with HIV and abdominal fat accumulation (48 of whom received study drug), deep visceral fat fell with a between-group effect of -42 cm2 (95% CI -71 to -14; P=.005) and liver fat measured by magnetic resonance spectroscopy went down (median change in lipid-to-water percentage -2.0% on tesamorelin against 0.9% on placebo, P=.003; net between-group effect -2.9%). The fat under the skin did not significantly change (between-group effect -6 cm2, 95% CI -19 to 7, P=0.29), and fat inside muscle cells did not change. The unfavorable signals are kept here: fasting glucose rose in the tesamorelin group at 2 weeks (between-group effect 7 mg/dL, 95% CI 1 to 14, P=.03) though changes at 6 months were not significant (P=.72 across time points), and HbA1c showed a small but statistically significant increase from baseline to 6 months (0.20% against 0.02%, between-group effect 0.19%, 95% CI 0.01 to 0.36, P=0.03). The authors themselves called this a preliminary study. human randomized double-blind placebo-controlled trial (n=50 randomized, 48 received study drug, 6 months) Preclinical moderate A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product. Open for the full finding and the paper it came from.

    In the literature

    Liver fat measured alongside deep abdominal fat

    In a 6-month double-blind randomized placebo-controlled trial of 50 adults with HIV and abdominal fat accumulation (48 of whom received study drug), deep visceral fat fell with a between-group effect of -42 cm2 (95% CI -71 to -14; P=.005) and liver fat measured by magnetic resonance spectroscopy went down (median change in lipid-to-water percentage -2.0% on tesamorelin against 0.9% on placebo, P=.003; net between-group effect -2.9%). The fat under the skin did not significantly change (between-group effect -6 cm2, 95% CI -19 to 7, P=0.29), and fat inside muscle cells did not change. The unfavorable signals are kept here: fasting glucose rose in the tesamorelin group at 2 weeks (between-group effect 7 mg/dL, 95% CI 1 to 14, P=.03) though changes at 6 months were not significant (P=.72 across time points), and HbA1c showed a small but statistically significant increase from baseline to 6 months (0.20% against 0.02%, between-group effect 0.19%, 95% CI 0.01 to 0.36, P=0.03). The authors themselves called this a preliminary study.^{References 11}

    Modelhuman randomized double-blind placebo-controlled trial (n=50 randomized, 48 received study drug, 6 months)

    Confidence: moderate

    A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product.

    Source

    Stanley TL, Feldpausch MN, Oh J, et al. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014;312(4):380-389. doi:10.1001/jama.2014.8334 (PMID 25038357; PMC4363137)

    PubMed 25038357

    How this citation was checked

    Re-resolved live in the source pass, including the full text. PubMed esummary and efetch on PMID 25038357 returned JAMA 2014 Jul 23-30;312(4):380-9, first author Stanley TL, DOI 10.1001/jama.2014.8334, PMCID PMC4363137. Crossref on the DOI independently returned JAMA, volume 312, issue 4, first page 380, issued 2014-07-23, first author Stanley Takara L. The VAT, liver fat and 2-week glucose figures came from the retrieved abstract. 3 items are not in the abstract, so the full text was pulled via NCBI efetch on PMC4363137 and read directly: the subcutaneous result with its between-group effect of -6 cm2 (95% CI -19, 7), P=0.29; the HbA1c increase from baseline to 6 months with its between-group effect of 0.19% (95% CI 0.01, 0.36), P=0.03; and the statement that intramyocellular lipid did not change. The same pass re-confirmed that the wrong PMID once attached to this paper, 25038356, resolves to MacPherson P et al., an unrelated HIV self-testing trial in Malawi, JAMA 2014;312(4):372-9, doi 10.1001/jama.2014.6493.

12. Studied for

    How fast it moves through the body

    A population pharmacokinetic analysis of 38 adults, some with HIV and some healthy, receiving daily subcutaneous tesamorelin for 14 consecutive days was best described by a one-compartment model with first-order and zero-order absorption and first-order elimination. Plasma clearance was estimated at 1,060 L/h (33.6% variation between individuals) and volume of distribution at 200 L (17.7%). Age, body size measures, race and health status were not related to the pharmacokinetic parameters within the ranges studied. The fraction absorbed by a first-order process was 13.1% higher on day 14 than on day 1. Note that this population model reports volume of distribution in liters while the approved labeling reports it in liters per kilogram; they are different quantities and should not be compared directly. human population pharmacokinetic modelling study (n=38 healthy adults and adults with HIV, 14 days) Preclinical moderate A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product. Open for the full finding and the paper it came from.

    In the literature

    How fast it moves through the body

    A population pharmacokinetic analysis of 38 adults, some with HIV and some healthy, receiving daily subcutaneous tesamorelin for 14 consecutive days was best described by a one-compartment model with first-order and zero-order absorption and first-order elimination. Plasma clearance was estimated at 1,060 L/h (33.6% variation between individuals) and volume of distribution at 200 L (17.7%). Age, body size measures, race and health status were not related to the pharmacokinetic parameters within the ranges studied. The fraction absorbed by a first-order process was 13.1% higher on day 14 than on day 1. Note that this population model reports volume of distribution in liters while the approved labeling reports it in liters per kilogram; they are different quantities and should not be compared directly.^{References 12}

    Modelhuman population pharmacokinetic modelling study (n=38 healthy adults and adults with HIV, 14 days)

    Confidence: moderate

    A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product.

    Source

    Gonzalez-Sales M, Barriere O, Tremblay PO, et al. Population pharmacokinetic analysis of tesamorelin in HIV-infected patients and healthy subjects. Clin Pharmacokinet. 2015;54(3):285-294. doi:10.1007/s40262-014-0202-x (PMID 25358450)

    PubMed 25358450

    How this citation was checked

    Re-resolved live in the source pass. PubMed efetch on PMID 25358450 returned Clin Pharmacokinet 2015 Mar;54(3):285-94, first author rendered as Gonzalez-Sales M (with an accent in the PubMed record), DOI 10.1007/s40262-014-0202-x, with the abstract supplying the 1,060 L/h clearance and 33.6% coefficient of variation, the 200 L volume and 17.7%, the covariate null result and the 13.1% figure. Crossref on the DOI independently returned Clinical Pharmacokinetics, volume 54, issue 3, pages 285-294, first author Gonzalez-Sales Mario.

13. Studied for

    What it does to the body's own growth hormone rhythm

    13 healthy men (mean age 45 years, mean BMI 27.3) received daily subcutaneous tesamorelin for 2 weeks, with overnight frequent blood sampling at baseline, after the 2 weeks, and after 2 weeks off it. The pre-specified primary endpoint was the change in mean overnight growth hormone, which rose (+0.5 plus or minus 0.1 micrograms per liter, P=0.004), as did average log10 growth hormone peak area (P=0.001) and basal growth hormone secretion (P=0.008). The authors concluded that it augments basal and pulsatile GH secretion. Among the secondary endpoints, IGF-I rose by 181 plus or minus 22 micrograms per liter (P<0.0001), while neither fasting glucose (P=0.93) nor insulin-stimulated glucose uptake measured by clamp (P=0.61) was significantly affected. human mechanistic study in healthy male volunteers (n=13, 2 weeks of exposure plus 2 weeks of withdrawal) Preclinical moderate A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product. Open for the full finding and the paper it came from.

    In the literature

    What it does to the body's own growth hormone rhythm

    13 healthy men (mean age 45 years, mean BMI 27.3) received daily subcutaneous tesamorelin for 2 weeks, with overnight frequent blood sampling at baseline, after the 2 weeks, and after 2 weeks off it. The pre-specified primary endpoint was the change in mean overnight growth hormone, which rose (+0.5 plus or minus 0.1 micrograms per liter, P=0.004), as did average log10 growth hormone peak area (P=0.001) and basal growth hormone secretion (P=0.008). The authors concluded that it augments basal and pulsatile GH secretion. Among the secondary endpoints, IGF-I rose by 181 plus or minus 22 micrograms per liter (P<0.0001), while neither fasting glucose (P=0.93) nor insulin-stimulated glucose uptake measured by clamp (P=0.61) was significantly affected.^{References 13}

    Modelhuman mechanistic study in healthy male volunteers (n=13, 2 weeks of exposure plus 2 weeks of withdrawal)

    Confidence: moderate

    A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product.

    Source

    Stanley TL, Chen CY, Branch KL, Makimura H, Grinspoon SK. Effects of a growth hormone-releasing hormone analog on endogenous GH pulsatility and insulin sensitivity in healthy men. J Clin Endocrinol Metab. 2011;96(1):150-158. doi:10.1210/jc.2010-1587 (PMID 20943777; PMC3038486)

    PubMed 20943777

    How this citation was checked

    Re-resolved live in the source pass. PubMed esummary and efetch on PMID 20943777 returned J Clin Endocrinol Metab 2011 Jan;96(1):150-8, author list Stanley TL, Chen CY, Branch KL, Makimura H, Grinspoon SK, DOI 10.1210/jc.2010-1587, PMCID PMC3038486. Crossref on the DOI independently returned The Journal of Clinical Endocrinology and Metabolism, volume 96, issue 1, pages 150-158, issued 2011-01, first author Stanley Takara L. The retrieved abstract states explicitly that the primary end point was change in mean overnight GH and lists insulin-stimulated glucose uptake among the SECONDARY end points, which is why an earlier draft's 'co-primary' framing was corrected; it also supplied the +0.5, +181, P=0.93 and P=0.61 results and the authors' own summary phrase.

14. Studied for

    Antibodies formed against it in the trial population

    The current FDA-approved prescribing information reports that in the clinical trials of the original formulation, anti-tesamorelin IgG antibodies were detected in 50% of the people who received it for 26 weeks and 47% of those who received it for 52 weeks. In the subset who had hypersensitivity reactions, anti-tesamorelin IgG antibodies were detected in 85%. Cross-reactivity to the body's own growth hormone-releasing hormone was observed in approximately 60% of those who developed anti-tesamorelin antibodies. The label also states that people with and without these antibodies had similar mean reductions in visceral fat and a similar IGF-1 response. This is an observed immunological finding in a drug-product trial population. human, pooled immunogenicity assessment across the clinical trial program, as reported in FDA prescribing information Preclinical moderate A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product. Open for the full finding and the paper it came from.

    In the literature

    Antibodies formed against it in the trial population

    The current FDA-approved prescribing information reports that in the clinical trials of the original formulation, anti-tesamorelin IgG antibodies were detected in 50% of the people who received it for 26 weeks and 47% of those who received it for 52 weeks. In the subset who had hypersensitivity reactions, anti-tesamorelin IgG antibodies were detected in 85%. Cross-reactivity to the body's own growth hormone-releasing hormone was observed in approximately 60% of those who developed anti-tesamorelin antibodies. The label also states that people with and without these antibodies had similar mean reductions in visceral fat and a similar IGF-1 response. This is an observed immunological finding in a drug-product trial population.^{References 14}

    Modelhuman, pooled immunogenicity assessment across the clinical trial program, as reported in FDA prescribing information

    Confidence: moderate

    A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product.

    Source

    EGRIFTA SV (tesamorelin) for injection, full prescribing information, section 12.6 Immunogenicity. Theratechnologies Inc. DailyMed SPL setid 3d783378-b02d-4f19-99dd-0fc91a042224

    Source

    How this citation was checked

    Re-fetched live in the source pass, and this entry's numbers were wrong in an earlier draft. The DailyMed structured product label was pulled from the API (setid 3d783378-b02d-4f19-99dd-0fc91a042224, HTTP 200) and section 12.6 read directly; the 50%, 47%, 85% and approximately 60% figures above are the label's own. An earlier draft gave these as 49.5%, 47.4% and 85.2% and placed immunogenicity at section 6.2; those falsely precise figures matched no retrievable source and were replaced with the label's own numbers at the label's own section number. On sourcing: an earlier draft cited this to a 2010 FDA accessdata PDF for application 022505, which does not serve the document, redirects to an FDA error page and returns HTTP 404. A DailyMed drug-name search for tesamorelin returns exactly 2 labels, EGRIFTA SV and EGRIFTA WR, and no others, so every FDA citation on this page points to a label a reader can actually open.

15. Studied for

    Liver-injury record

    The NIH LiverTox monograph states that in clinical trials in adults with HIV-associated lipodystrophy, tesamorelin use was not associated with de novo elevations in serum enzymes and, in the monograph's own hedged wording, 'in some studies, was associated with decreases in preexisting ALT elevations'. It further states that instances of clinically apparent liver injury attributable to tesamorelin use have not been reported, and assigns likelihood score E, meaning an unlikely cause of clinically apparent liver injury. Absence of a recorded harm signal is not a protective effect, and nothing here should be read as one. human, curated systematic literature review (NIH NIDDK LiverTox monograph) Preclinical moderate A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product. Open for the full finding and the paper it came from.

    In the literature

    Liver-injury record

    The NIH LiverTox monograph states that in clinical trials in adults with HIV-associated lipodystrophy, tesamorelin use was not associated with de novo elevations in serum enzymes and, in the monograph's own hedged wording, 'in some studies, was associated with decreases in preexisting ALT elevations'. It further states that instances of clinically apparent liver injury attributable to tesamorelin use have not been reported, and assigns likelihood score E, meaning an unlikely cause of clinically apparent liver injury. Absence of a recorded harm signal is not a protective effect, and nothing here should be read as one.^{References 15}

    Modelhuman, curated systematic literature review (NIH NIDDK LiverTox monograph)

    Confidence: moderate

    A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product.

    Source

    LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Tesamorelin. [Updated 2018 Oct 20]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. NCBI Bookshelf NBK548730 (PMID 31644039)

    PubMed 31644039

    How this citation was checked

    Re-fetched live in the source pass. https://www.ncbi.nlm.nih.gov/books/NBK548730/ returned HTTP 200 and the monograph text was read directly. The hedge 'in some studies' had been dropped in an earlier draft and is restored above. The same page gives the update date 20 October 2018, Bookshelf ID NBK548730 and PMID 31644039, which are now in the citation. Where this page writes 'use', the monograph writes a word that is on the store-wide banned list; the substitution rule is recorded in _render_edits and the monograph's meaning is unchanged.

16. Studied for

    Animal toxicology on the regulatory record

    Per the current FDA-approved prescribing information: giving tesamorelin acetate to rats during organogenesis and lactation produced hydrocephaly, fluid on the brain, in the offspring at approximately 2 and 4 times the clinical exposure respectively, based on measured drug exposure. During organogenesis, lower exposures of approximately 0.1 to 1 times the clinical exposure caused delayed skull bone formation in rats. No adverse developmental effects occurred in rabbits at up to approximately 500 times the clinical exposure. No potential for genetic damage was revealed in a battery of tests including gene mutations in bacteria (the Ames test), gene mutations in cultured hamster cells, and chromosomal damage in bone marrow cells in mice. There was no effect on fertility in male or female rats at exposures approximately equal to the clinical exposure. Lifetime cancer studies in rodents have not been conducted. This is regulatory toxicology on the record for the finished drug product, reported as such. It is not a statement about people, and the animal exposure amounts the label also prints are deliberately not reproduced here. IN VITRO rat, mouse and rabbit in vivo studies plus in vitro bacterial and mammalian-cell genotoxicity assays, as reported in FDA prescribing information Preclinical moderate A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product. Open for the full finding and the paper it came from.

    In the literature

    Animal toxicology on the regulatory record

    Per the current FDA-approved prescribing information: giving tesamorelin acetate to rats during organogenesis and lactation produced hydrocephaly, fluid on the brain, in the offspring at approximately 2 and 4 times the clinical exposure respectively, based on measured drug exposure. During organogenesis, lower exposures of approximately 0.1 to 1 times the clinical exposure caused delayed skull bone formation in rats. No adverse developmental effects occurred in rabbits at up to approximately 500 times the clinical exposure. No potential for genetic damage was revealed in a battery of tests including gene mutations in bacteria (the Ames test), gene mutations in cultured hamster cells, and chromosomal damage in bone marrow cells in mice. There was no effect on fertility in male or female rats at exposures approximately equal to the clinical exposure. Lifetime cancer studies in rodents have not been conducted. This is regulatory toxicology on the record for the finished drug product, reported as such. It is not a statement about people, and the animal exposure amounts the label also prints are deliberately not reproduced here.^{References 14}

    Modelrat, mouse and rabbit in vivo studies plus in vitro bacterial and mammalian-cell genotoxicity assays, as reported in FDA prescribing information

    Confidence: moderate

    A well-described result from a single controlled study with several independent outcome measures, or a finding reported on the regulatory record for the approved drug product.

    Source

    EGRIFTA SV (tesamorelin) for injection, full prescribing information, sections 8.1 Pregnancy and 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Theratechnologies Inc. DailyMed SPL setid 3d783378-b02d-4f19-99dd-0fc91a042224

    Source

    How this citation was checked

    Re-fetched live in the source pass. From the same DailyMed structured product label (HTTP 200), section 8.1 was read verbatim, including the hydrocephaly finding at approximately 2 and 4 times the clinical exposure based on measured drug exposure (AUC), the delayed skull ossification at approximately 0.1 to 1 times, and the absence of adverse developmental effects in rabbits up to approximately 500 times. Section 13.1 states that life-time carcinogenicity studies in rodents have not been conducted with tesamorelin acetate, names the Ames test, hamster CHOK1 cells and bone marrow cells in mice, and states there was no effect on fertility in male or female rats. The exposure multiples above are transcribed from that text; the per-kilogram animal amounts the label also gives are intentionally not reproduced.

17. Studied for

    Liver enzymes in the people whose deep fat responded

    A post hoc analysis of the 2 phase 3 trials (806 participants) looked at the people receiving tesamorelin who started with an ALT or AST above 30 U/L. Those who met the FDA-defined responder threshold of at least an 8% reduction in visceral fat showed larger falls in ALT (-8.9 plus or minus 22.6 against 1.4 plus or minus 34.7 U/L, P=0.004) and AST (-3.8 plus or minus 12.9 against 0.4 plus or minus 22.4 U/L, P=0.04) than non-responders over 26 weeks. This compares responders with non-responders inside the active arm rather than against placebo, so it describes an association and not a between-group effect. human post hoc responder analysis of 2 randomized phase 3 trials (n=806 source population, 26 and 52 weeks) Preclinical preliminary A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Liver enzymes in the people whose deep fat responded

    A post hoc analysis of the 2 phase 3 trials (806 participants) looked at the people receiving tesamorelin who started with an ALT or AST above 30 U/L. Those who met the FDA-defined responder threshold of at least an 8% reduction in visceral fat showed larger falls in ALT (-8.9 plus or minus 22.6 against 1.4 plus or minus 34.7 U/L, P=0.004) and AST (-3.8 plus or minus 12.9 against 0.4 plus or minus 22.4 U/L, P=0.04) than non-responders over 26 weeks. This compares responders with non-responders inside the active arm rather than against placebo, so it describes an association and not a between-group effect.^{References 16}

    Modelhuman post hoc responder analysis of 2 randomized phase 3 trials (n=806 source population, 26 and 52 weeks)

    Confidence: preliminary

    A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Fourman LT, Czerwonka N, Feldpausch MN, et al. Visceral fat reduction with tesamorelin is associated with improved liver enzymes in HIV. AIDS. 2017;31(16):2253-2259. doi:10.1097/QAD.0000000000001614 (PMID 28832410; PMC5633509)

    PubMed 28832410

    How this citation was checked

    Re-resolved live in the source pass. PubMed efetch on PMID 28832410 returned AIDS 2017 Oct 23;31(16):2253-2259, first author Fourman LT, DOI 10.1097/QAD.0000000000001614, PMCID PMC5633509, with the abstract supplying both enzyme figures and confirming the responder-against-nonresponder design and the a priori FDA 8% responder definition. Crossref on the DOI independently returned AIDS, volume 31, issue 16, pages 2253-2259, issued 2017-10-23, first author Fourman Lindsay T.

18. Studied for

    Fat inside the trunk muscles, and muscle size

    An exploratory secondary analysis pooling 2 completed randomized trials compared tesamorelin responders, meaning a visceral fat decrease of at least 8% (n=193), against placebo participants (n=148) over 26 weeks, using CT imaging at the L4-L5 level. In models adjusted for baseline differences and study arm, tesamorelin was associated with greater increases in the density of 4 trunk muscle groups (coefficients 1.56 to 4.86 Hounsfield units, all p<0.005), which the authors read as less fat marbled between the muscle fibers, and with increases in the total area of the rectus and psoas muscles (0.44 and 0.46 cm2, p<0.005) and in the lean muscle area of all 4 trunk groups (0.64 to 1.08 cm2, p<0.005). This is exploratory and secondary, restricted to responders in an HIV study population, and it reports no strength or performance outcome at all. human exploratory secondary analysis of 2 randomized controlled trials (n=341 analyzed: 193 responders, 148 placebo; 26 weeks) Preclinical preliminary A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Fat inside the trunk muscles, and muscle size

    An exploratory secondary analysis pooling 2 completed randomized trials compared tesamorelin responders, meaning a visceral fat decrease of at least 8% (n=193), against placebo participants (n=148) over 26 weeks, using CT imaging at the L4-L5 level. In models adjusted for baseline differences and study arm, tesamorelin was associated with greater increases in the density of 4 trunk muscle groups (coefficients 1.56 to 4.86 Hounsfield units, all p<0.005), which the authors read as less fat marbled between the muscle fibers, and with increases in the total area of the rectus and psoas muscles (0.44 and 0.46 cm2, p<0.005) and in the lean muscle area of all 4 trunk groups (0.64 to 1.08 cm2, p<0.005). This is exploratory and secondary, restricted to responders in an HIV study population, and it reports no strength or performance outcome at all.^{References 17}

    Modelhuman exploratory secondary analysis of 2 randomized controlled trials (n=341 analyzed: 193 responders, 148 placebo; 26 weeks)

    Confidence: preliminary

    A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Adrian S, Scherzinger A, Sanyal A, et al. The growth hormone releasing hormone analogue, tesamorelin, decreases muscle fat and increases muscle area in adults with HIV. J Frailty Aging. 2019;8(3):154-159. doi:10.14283/jfa.2018.45 (PMID 31237318; PMC6766405)

    PubMed 31237318

    How this citation was checked

    Re-resolved live in the source pass, and this is the citation an earlier draft had on the wrong journal. PubMed esummary and efetch on PMID 31237318 return The Journal of Frailty and Aging 2019;8(3):154-159, DOI 10.14283/jfa.2018.45, PMCID PMC6766405, first author Adrian S, not J Nutr Health Aging. Crossref on the DOI independently returned The Journal of Frailty and Aging, volume 8, issue 3, pages 154-159, issued 2019-07, first author Adrian S., confirming issue 3. All effect sizes above were transcribed from the retrieved abstract.

19. Studied for

    Fat quality as distinct from fat quantity

    In a secondary analysis of participants from 2 completed placebo-controlled randomized trials (193 tesamorelin responders and 148 placebo participants), the density of visceral and subcutaneous fat on CT was read by a single blinded central reader. Over 26 weeks, mean density rose in the participants receiving tesamorelin only (visceral: +6.2 [SD 8.7] Hounsfield units against +0.3 [4.2] on placebo, P<0.0001; subcutaneous: +4.0 [8.7] against +0.3 [4.8], P<0.0001), and the effects held after controlling for baseline density and area and for change in area. Because greater density is interpreted as smaller fat cells, the authors describe this as improved fat quality independent of any change in fat quantity, within the responder subgroup. human secondary analysis of 2 randomized placebo-controlled trials (n=341, 26 weeks) Preclinical preliminary A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Fat quality as distinct from fat quantity

    In a secondary analysis of participants from 2 completed placebo-controlled randomized trials (193 tesamorelin responders and 148 placebo participants), the density of visceral and subcutaneous fat on CT was read by a single blinded central reader. Over 26 weeks, mean density rose in the participants receiving tesamorelin only (visceral: +6.2 [SD 8.7] Hounsfield units against +0.3 [4.2] on placebo, P<0.0001; subcutaneous: +4.0 [8.7] against +0.3 [4.8], P<0.0001), and the effects held after controlling for baseline density and area and for change in area. Because greater density is interpreted as smaller fat cells, the authors describe this as improved fat quality independent of any change in fat quantity, within the responder subgroup.^{References 18}

    Modelhuman secondary analysis of 2 randomized placebo-controlled trials (n=341, 26 weeks)

    Confidence: preliminary

    A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Lake JE, La K, Erlandson KM, et al. Tesamorelin improves fat quality independent of changes in fat quantity. AIDS. 2021;35(9):1395-1402. doi:10.1097/QAD.0000000000002897 (PMID 33756511; PMC8243807)

    PubMed 33756511

    How this citation was checked

    Re-resolved live in the source pass. PubMed efetch on PMID 33756511 returned AIDS 2021 Jul 15;35(9):1395-1402, first author Lake JE, DOI 10.1097/QAD.0000000000002897, PMCID PMC8243807, and the abstract supplied every density figure and P value above, plus the 193-responder and 148-placebo counts and the blinded central reader. Crossref on the DOI independently returned AIDS, volume 35, issue 9, pages 1395-1402, issued 2021-03-23, first author Lake Jordan E.

20. Studied for

    Matching proteins measured in the blood

    A focused look at 9 blood proteins, chosen because they matched the top genes in the gene sets that had moved, found reductions on tesamorelin against placebo in vascular endothelial growth factor A (log2 fold change -0.20 plus or minus 0.35 against 0.05 plus or minus 0.34, P=0.02), transforming growth factor beta 1 (-0.35 plus or minus 0.56 against -0.05 plus or minus 0.43, P=0.05) and macrophage colony stimulating factor 1 (-0.17 plus or minus 0.21 against 0.02 plus or minus 0.20, P=0.004). Among the participants receiving tesamorelin, the falls in VEGFA (r=0.62, P=0.006) and CSF1 (r=0.50, P=0.04) correlated with a decline in NAFLD activity score. These are exploratory biomarker observations inside a single trial, not demonstrated clinical anti-inflammatory outcomes. human targeted blood-protein analysis nested inside a randomized controlled trial (n=44 with paired samples at baseline and 12 months: 20 tesamorelin, 24 placebo, drawn from the 61-participant trial) Preclinical preliminary A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Matching proteins measured in the blood

    A focused look at 9 blood proteins, chosen because they matched the top genes in the gene sets that had moved, found reductions on tesamorelin against placebo in vascular endothelial growth factor A (log2 fold change -0.20 plus or minus 0.35 against 0.05 plus or minus 0.34, P=0.02), transforming growth factor beta 1 (-0.35 plus or minus 0.56 against -0.05 plus or minus 0.43, P=0.05) and macrophage colony stimulating factor 1 (-0.17 plus or minus 0.21 against 0.02 plus or minus 0.20, P=0.004). Among the participants receiving tesamorelin, the falls in VEGFA (r=0.62, P=0.006) and CSF1 (r=0.50, P=0.04) correlated with a decline in NAFLD activity score. These are exploratory biomarker observations inside a single trial, not demonstrated clinical anti-inflammatory outcomes.^{References 19}

    Modelhuman targeted blood-protein analysis nested inside a randomized controlled trial (n=44 with paired samples at baseline and 12 months: 20 tesamorelin, 24 placebo, drawn from the 61-participant trial)

    Confidence: preliminary

    A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Fourman LT, Stanley TL, Billingsley JM, et al. Delineating tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach. Sci Rep. 2021;11(1):10485. doi:10.1038/s41598-021-89966-y (PMID 34006921; PMC8131688)

    PubMed 34006921

    How this citation was checked

    Re-resolved live in the source pass, abstract and full text. PubMed efetch on PMID 34006921 returned Sci Rep 2021 May 18;11(1):10485, first authors Fourman LT and Stanley TL (marked equal contributors), DOI 10.1038/s41598-021-89966-y, PMCID PMC8131688, with an abstract containing every effect size and P value quoted above verbatim. Crossref on the DOI independently returned Scientific Reports, volume 11, issue 1, issued 2021-05-18, first author Fourman Lindsay T. The abstract carries no sample size, so PMC8131688 was pulled via NCBI efetch to close that gap: of 61 participants in the parent randomized controlled trial, 58 had a plasma protein panel at baseline and 44 of those (20 assigned to tesamorelin, 24 to placebo) had it repeated at 12 months. Noted for fairness: the paper itself describes the P=0.05 TGFB1 result as a significant reduction, so nothing is overstated here.

21. Studied for

    Which genes changed inside the liver

    Using paired liver biopsy samples taken from the randomized liver-fat trial, a gene-expression analysis found that tesamorelin turned up gene sets involved in oxidative phosphorylation, the cell's energy production machinery, and turned down gene sets contributing to inflammation, to the repair of damaged tissue, and to cell division. Among the people who received tesamorelin, these expression changes correlated with an improved fibrosis-related gene score. The authors present this as a mechanistic basis for what was seen clinically, not as a clinical outcome in its own right. human paired liver-biopsy gene-expression analysis nested inside a randomized controlled trial (n=39 with usable RNA-Seq data: 18 tesamorelin, 21 placebo) Preclinical preliminary A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Which genes changed inside the liver

    Using paired liver biopsy samples taken from the randomized liver-fat trial, a gene-expression analysis found that tesamorelin turned up gene sets involved in oxidative phosphorylation, the cell's energy production machinery, and turned down gene sets contributing to inflammation, to the repair of damaged tissue, and to cell division. Among the people who received tesamorelin, these expression changes correlated with an improved fibrosis-related gene score. The authors present this as a mechanistic basis for what was seen clinically, not as a clinical outcome in its own right.^{References 20}

    Modelhuman paired liver-biopsy gene-expression analysis nested inside a randomized controlled trial (n=39 with usable RNA-Seq data: 18 tesamorelin, 21 placebo)

    Confidence: preliminary

    A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Fourman LT, Billingsley JM, Agyapong G, et al. Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD. JCI Insight. 2020;5(16):e140134. doi:10.1172/jci.insight.140134 (PMID 32701508; PMC7455119)

    PubMed 32701508

    How this citation was checked

    Re-resolved live in the source pass, abstract and full text. PubMed esummary and efetch on PMID 32701508 returned JCI Insight 2020 Aug 20;5(16):e140134, first author Fourman LT, DOI 10.1172/jci.insight.140134, PMCID PMC7455119, with an abstract matching the oxidative-phosphorylation-up and inflammation, repair and cell-division-down description. Crossref on the DOI independently returned JCI Insight, volume 5, issue 16, issued 2020-08-20, first author Fourman Lindsay T. The abstract gives no sample size, so PMC7455119 was pulled via NCBI efetch and read: 19 tesamorelin and 24 placebo participants had paired liver specimens, 4 were excluded for poor RNA samples, resulting in 18 randomized to tesamorelin and 21 randomized to placebo with RNA-Seq data included in the analysis. One clause of this abstract's result is deliberately not reproduced on this page; see verification.omitted_claims.

22. Studied for

    Phosphocreatine recovery and the IGF-I change, in adults with reduced growth hormone

    39 adults with obesity and reduced growth hormone secretion, confirmed by a stimulation test, underwent phosphorus magnetic resonance spectroscopy as part of a 12-month double-blind randomized placebo-controlled trial of tesamorelin against placebo, with phosphocreatine recovery after submaximal exercise measured at baseline and at 12 months. Tesamorelin produced a greater rise in IGF-I than placebo (change 102.9 plus or minus 31.8 against 22.8 plus or minus 8.9 micrograms per liter, P=.02). Increases in IGF-I were positively associated with improvements in phosphocreatine recovery, a proxy for how fast muscle mitochondria recharge (R=0.56, P=.01 overall; R=0.71, P=.03 among the participants receiving tesamorelin), and the association held after adjustment. Read this precisely: the published result is a correlation between the IGF-I change and how fast phosphocreatine recovered. The abstract reports no significant tesamorelin-against-placebo effect on phosphocreatine recovery itself, and that distinction is not blurred here. human 12-month double-blind randomized placebo-controlled trial with a magnetic resonance spectroscopy substudy in adults with obesity and reduced growth hormone (n=39) Preclinical preliminary A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Phosphocreatine recovery and the IGF-I change, in adults with reduced growth hormone

    39 adults with obesity and reduced growth hormone secretion, confirmed by a stimulation test, underwent phosphorus magnetic resonance spectroscopy as part of a 12-month double-blind randomized placebo-controlled trial of tesamorelin against placebo, with phosphocreatine recovery after submaximal exercise measured at baseline and at 12 months. Tesamorelin produced a greater rise in IGF-I than placebo (change 102.9 plus or minus 31.8 against 22.8 plus or minus 8.9 micrograms per liter, P=.02). Increases in IGF-I were positively associated with improvements in phosphocreatine recovery, a proxy for how fast muscle mitochondria recharge (R=0.56, P=.01 overall; R=0.71, P=.03 among the participants receiving tesamorelin), and the association held after adjustment. Read this precisely: the published result is a correlation between the IGF-I change and how fast phosphocreatine recovered. The abstract reports no significant tesamorelin-against-placebo effect on phosphocreatine recovery itself, and that distinction is not blurred here.^{References 21}

    Modelhuman 12-month double-blind randomized placebo-controlled trial with a magnetic resonance spectroscopy substudy in adults with obesity and reduced growth hormone (n=39)

    Confidence: preliminary

    A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Makimura H, Murphy CA, Feldpausch MN, Grinspoon SK. The effects of tesamorelin on phosphocreatine recovery in obese subjects with reduced GH. J Clin Endocrinol Metab. 2014;99(1):338-343. doi:10.1210/jc.2013-3436 (PMID 24178787; PMC3879673)

    PubMed 24178787

    How this citation was checked

    Re-resolved live in the source pass. PubMed efetch on PMID 24178787 returned J Clin Endocrinol Metab 2014 Jan;99(1):338-43, authors Makimura H, Murphy CA, Feldpausch MN, Grinspoon SK, DOI 10.1210/jc.2013-3436, PMCID PMC3879673. Crossref on the DOI independently returned The Journal of Clinical Endocrinology and Metabolism, volume 99, issue 1, pages 338-343, issued 2014-01, first author Makimura Hideo. The retrieved abstract reports the IGF-I between-group difference (P=.02) and the 2 IGF-I-to-phosphocreatine correlations (R=0.56, P=.01; R=0.71, P=.03) and states no significant effect on phosphocreatine recovery itself, which is why the finding is worded as a correlation. An earlier draft closed this entry by calling it the main controlled dataset outside an HIV population besides the diabetes trial; that was false against the record's own contents, since the 152-participant cognition trial is also entirely outside an HIV population, so the sentence was deleted.

23. Studied for

    Whether it still works on modern HIV drug regimens

    Because the phase 3 trials ran before integrase inhibitors became standard HIV care, the investigators analyzed the participants who were on integrase-inhibitor regimens inside the 61-person randomized double-blind liver-fat trial. Among 38 such participants, 15 on tesamorelin and 16 on placebo completed the 12-month study. Tesamorelin was associated with declines in visceral fat (median -25 [IQR -93 to -2] against +14 [3 to 41] cm2, P=0.001), liver fat (-4.2% [-12.3% to -2.7%] against -0.5% [-3.9% to 2.7%], P=0.01) and the trunk-to-limb fat ratio (-0.1 against 0.0, P=0.03), with a similar frequency of adverse events, including high blood sugar, between groups. This is a small subgroup of a single trial. human subgroup analysis inside a randomized double-blind placebo-controlled trial (n=38 on integrase-inhibitor regimens, 31 completers, 12 months) Preclinical preliminary A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Whether it still works on modern HIV drug regimens

    Because the phase 3 trials ran before integrase inhibitors became standard HIV care, the investigators analyzed the participants who were on integrase-inhibitor regimens inside the 61-person randomized double-blind liver-fat trial. Among 38 such participants, 15 on tesamorelin and 16 on placebo completed the 12-month study. Tesamorelin was associated with declines in visceral fat (median -25 [IQR -93 to -2] against +14 [3 to 41] cm2, P=0.001), liver fat (-4.2% [-12.3% to -2.7%] against -0.5% [-3.9% to 2.7%], P=0.01) and the trunk-to-limb fat ratio (-0.1 against 0.0, P=0.03), with a similar frequency of adverse events, including high blood sugar, between groups. This is a small subgroup of a single trial.^{References 22}

    Modelhuman subgroup analysis inside a randomized double-blind placebo-controlled trial (n=38 on integrase-inhibitor regimens, 31 completers, 12 months)

    Confidence: preliminary

    A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    Russo SC, Ockene MW, Arpante AK, et al. Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors. AIDS. 2024;38(12):1758-1764. doi:10.1097/QAD.0000000000003965 (PMID 38905488; PMC11365754)

    PubMed 38905488

    How this citation was checked

    Re-resolved live in the source pass. PubMed efetch on PMID 38905488 returned AIDS 2024 Oct 1;38(12):1758-1764, first author Russo SC, DOI 10.1097/QAD.0000000000003965, PMCID PMC11365754, and the abstract supplied the subgroup sizes and all 3 medians with their P values. Crossref on the DOI independently returned AIDS, volume 38, issue 12, pages 1758-1764, issued 2024-06-20, first author Russo Samuel C. One rigor claim was removed on that reading: the abstract says only that the authors leveraged a randomized double-blind trial of 61 people with HIV and calls this the current analysis, with nothing supporting pre-specification, so an earlier draft's description of this as a pre-specified subgroup was deleted.

24. Studied for

    Receptor-level mechanism, in cultured cells

    The current FDA-approved prescribing information states that in vitro, meaning in cultured cells rather than in an animal or a person, tesamorelin binds and stimulates human GRF receptors with similar potency as endogenous GRF. The same section describes GRF, also called GHRH, as a hypothalamic peptide acting on pituitary somatotroph cells to stimulate the synthesis and pulsatile release of the body's own growth hormone. This is a cell-level binding and stimulation characterization only. It carries no functional or clinical outcome by itself. IN VITRO in vitro receptor binding and stimulation in cultured cells, as characterized in FDA prescribing information Preclinical preliminary A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference. Open for the full finding and the paper it came from.

    In the literature

    Receptor-level mechanism, in cultured cells

    The current FDA-approved prescribing information states that in vitro, meaning in cultured cells rather than in an animal or a person, tesamorelin binds and stimulates human GRF receptors with similar potency as endogenous GRF. The same section describes GRF, also called GHRH, as a hypothalamic peptide acting on pituitary somatotroph cells to stimulate the synthesis and pulsatile release of the body's own growth hormone. This is a cell-level binding and stimulation characterization only. It carries no functional or clinical outcome by itself.^{References 14}

    Modelin vitro receptor binding and stimulation in cultured cells, as characterized in FDA prescribing information

    Confidence: preliminary

    A single study, a secondary or post hoc analysis nested inside a larger trial, an early mechanistic observation, or a result whose interpretation is the authors' own inference.

    Source

    EGRIFTA SV (tesamorelin) for injection, full prescribing information, section 12.1 Mechanism of Action. Theratechnologies Inc. DailyMed SPL setid 3d783378-b02d-4f19-99dd-0fc91a042224

    Source

    How this citation was checked

    Re-fetched live in the source pass. The structured product label was pulled from the DailyMed API (setid 3d783378-b02d-4f19-99dd-0fc91a042224, HTTP 200) and section 12.1 read directly: in vitro, tesamorelin binds and stimulates human GRF receptors with similar potency as the endogenous GRF, and growth hormone-releasing factor, also known as growth hormone-releasing hormone, is a hypothalamic peptide that acts on the pituitary somatotroph cells to stimulate the synthesis and pulsatile release of endogenous growth hormone. The identical text appears in the EGRIFTA WR label (setid 839334d3-8c1d-4c26-9036-2ab524a6ea75, also HTTP 200). The human-facing DailyMed page for each setid was checked separately and returns HTTP 200.

5 strong / 11 moderate / 8 preliminaryRated by how many independent labs and how many kinds of experiment found the same thing.