Tesamorelin

In a pooled analysis of two 26-week randomised, double-blind, placebo-controlled phase 3 trials in 806 adults with HIV and excess abdominal fat, visceral adipose tissue fell by 24 +/- 41 cm2 on tesamorelin versus a 2 +/- 35 cm2 increase on placebo (P<0.001; treatment effect -15.4%), while abdominal subcutaneous fat was unchanged (-2 +/- 32 vs 2 +/- 29 cm2, P=0.08).⁹

In the 26-week randomised, double-blind registrational trial in 412 adults with HIV and abdominal fat accumulation, visceral adipose tissue fell 15.2% on tesamorelin and rose 5.0% on placebo, triglycerides fell 50 mg/dL versus a 9 mg/dL rise, the total-cholesterol-to-HDL ratio fell 0.31 versus a 0.21 rise, and IGF-1 rose 81.0% versus a 5.0% fall (P<0.001 for all).⁶

In a 12-month randomised, double-blind, multicentre trial in 61 people with HIV and non-alcoholic fatty liver disease, hepatic fat fraction fell by an absolute 4.1% more than placebo (95% CI -7.6 to -0.7, P=0.018), a 37% relative reduction, and 35% of tesamorelin recipients versus 4% on placebo reached a hepatic fat fraction below 5% (P=0.0069).¹⁰

In the 26-week extension of a phase 3 trial that randomised 410 adults with HIV and central fat accumulation, the subgroup rerandomised to stay on tesamorelin held visceral adipose tissue 18% below baseline over 52 weeks (P<0.001 versus baseline) and triglycerides 51 mg/dL below baseline (P<0.001), while visceral fat reaccumulated in participants switched to placebo — the effect does not outlast the exposure.¹¹

A 2026 random-effects meta-analysis of five randomised controlled trials in adults with HIV-associated lipodystrophy found tesamorelin reduced visceral adipose tissue by 27.71 cm2 (95% CI -38.37 to -17.06), hepatic fat by 4.28 percentage points (95% CI -6.31 to -2.24) and waist circumference by 1.61 cm versus placebo, and increased lean body mass by 1.42 kg (95% CI 1.13 to 1.71), with no significant change in subcutaneous adipose tissue or BMI.¹²

In a 12-month randomised, double-blind, placebo-controlled trial in 60 abdominally obese adults with reduced growth hormone secretion, tesamorelin lowered visceral adipose tissue by 35 cm2 (95% CI -58 to -12, P=0.003), carotid intima-media thickness by 0.04 mm (95% CI -0.07 to -0.01, P=0.02), log C-reactive protein (P=0.04) and triglycerides by 37 mg/dL (95% CI -67 to -7, P=0.02) relative to placebo, with no change in subcutaneous adipose tissue, fasting glucose, 2-hour glucose or glycated haemoglobin.¹³

On paired liver biopsies from a 12-month randomised, double-blind trial in 61 people with HIV and non-alcoholic fatty liver disease, fibrosis progressed at least one stage in 2 of 19 tesamorelin recipients versus 9 of 24 on placebo (10.5% vs 37.5%, P=0.04). The NAFLD activity score did not differ (effect size -0.3, 95% CI -1.0 to 0.5), and existing fibrosis did not improve (2 vs 3 participants, P=0.71).¹⁰

In a secondary CT analysis of two randomised trials in adults with HIV and abdominal obesity, comparing 193 tesamorelin responders whose visceral fat fell at least 8% with 148 placebo participants, 26 weeks of treatment increased the density of four trunk muscle groups by 1.56 to 4.86 Hounsfield units and lean muscle area by 0.64 to 1.08 cm2 (all P<0.005). Restricting to responders makes this not a randomised comparison.¹⁴

In an uncontrolled, single-arm open-label study, 13 healthy men (mean age 45 years) took tesamorelin daily for two weeks; against their own baselines, mean overnight growth hormone rose by 0.5 +/- 0.1 microgram/L (P=0.004), basal secretion by 0.008 +/- 0.003 microgram/L per minute (P=0.008) and IGF-1 by 181 +/- 22 microgram/L (P<0.0001), while insulin-stimulated glucose uptake on euglycaemic hyperinsulinaemic clamp was unchanged (P=0.61). There was no placebo group.⁵

In non-clinical characterisation, adding the trans-3-hexenoyl moiety to Tyr1 of hGRF(1-44) made the peptide resistant to dipeptidyl aminopeptidase-IV and slowed its degradation in rat, dog and human plasma; in pigs, rats and dogs, repeated intravenous or subcutaneous dosing up to 600 microgram/kg markedly raised plasma growth hormone and IGF-1, with an apparent elimination half-life in dogs of 21 to 45 minutes.¹

In a 20-week randomised, double-blind, placebo-controlled trial in 152 adults aged 55 to 87, of whom 66 had mild cognitive impairment, tesamorelin produced a favourable effect on a composite cognitive outcome in intention-to-treat analysis (P=0.03); of the three pre-specified composites only executive function reached significance (P=0.005), verbal memory showed a non-significant trend (P=0.08) and no treatment effect on visual memory was reported. IGF-1 rose 117%, remaining within the physiological range, and percent body fat fell 7.4%.¹⁵

In a 6-month open-label phase 2 trial in 73 virally suppressed people with HIV and abdominal obesity, tesamorelin reduced waist circumference by a median 2.7 cm more than standard of care (P=0.015), but the between-group difference in neurocognitive performance was not significant (P=0.673); the trial was underpowered and had no placebo arm.¹⁶