Tesamorelin

Egrifta has had three FDA-approved formulations: the original Egrifta (2010), Egrifta SV (2019, smaller-volume reconstituted form) and Egrifta WR (2024–25, water-reconstituted at-home form). They deliver the same active molecule and are not freely interchangeable on a like-for-like basis. The European Medicines Agency never approved tesamorelin, Theratechnologies withdrew the European marketing application in 2010 after the CHMP raised concerns about the size of the benefit relative to the risks in the European HIV-LD population.

The evidence in the licensed indication is genuinely strong; outside it, there is almost nothing. The pivotal programme was two multicentre, randomised, double-blind, placebo-controlled Phase 3 trials in HIV-associated lipodystrophy. Falutz et al. (NEJM 2007) randomised 412 adults to tesamorelin 2 mg daily or placebo for 26 weeks and reported a mean ~15% reduction in visceral adipose tissue by CT versus a small gain on placebo, with subcutaneous fat largely preserved. The pooled Phase 3 analysis with safety extension (Falutz et al., JAIDS 2010) confirmed durability and tolerability over 52 weeks. Stanley TL et al. (JAMA 2014) showed visceral fat reduction plus modest liver-fat reduction in a separate HIV cohort; Stanley et al. (Lancet HIV 2019) extended the liver-fat finding in HIV-NAFLD. The honest caveats: the pivotal programme was sponsor-run (Theratechnologies); all the Phase 3 data is in adults with HIV; long-term safety beyond ~1 year is thin; there is a transient insulin-resistance signal that makes it unsuitable for adults with poorly-controlled diabetes; and the EMA never approved it. Critically, there is no Phase 3 evidence for tesamorelin in adults without HIV-associated lipodystrophy, the body-recomposition use case rests on extrapolation, not trials.

For information only, tesamorelin is a prescription-only medicine and dosing for the approved indication is set by a clinician. The FDA-approved label specifies 2 mg subcutaneously once daily for adults with HIV-associated lipodystrophy. The Egrifta SV (2019) and Egrifta WR (2024–25) reformulations deliver the bioactive equivalent through smaller reconstituted volumes (1.4 mg and 1.28 mg per dose respectively) and are administered once daily. Off-label "performance" protocols varying from 1–2 mg daily are common in non-medical settings but have not been validated in any trial, and the IGF-1 response and glucose effects in a non-HIV population may differ from what was characterised in the Phase 3 programme. This is not an instruction to dose: tesamorelin is a prescription medicine in every regulated market, supply outside the prescription channel is unverified, and clinician monitoring of fasting glucose, HbA1c and IGF-1 is the floor for anyone choosing to use it.

The commonest adverse effects in the Phase 3 programme were injection-site reactions (redness, swelling, itching), arthralgia, myalgia, peripheral oedema and flushing, the usual class effects of pushing the GH/IGF-1 axis upwards. The more serious concerns are also axis-mediated: transient insulin resistance with modest increases in fasting glucose and HbA1c, fluid retention, carpal-tunnel-like symptoms, and the theoretical risk of accelerating active malignancy via IGF-1 (the label contraindicates use in active malignancy). The FDA label carries warnings on glucose intolerance and diabetes, acute critical illness, and hypersensitivity (including rare anaphylaxis). Tesamorelin is contraindicated in pregnancy, in disrupted hypothalamic–pituitary axis (e.g. hypophysectomy, hypopituitarism, pituitary tumour or surgery) and during acute critical illness. The IGF-1 elevation that does the work is the same axis implicated in malignancy if pushed chronically; the durations actually studied are short, a year or less in the main programme.