Egrifta (Tesamorelin) Month-by-Month: What to Expect in the First 3 Months

Early tolerability: injection sites, fluid, and a two-week glucose signal

Injection-site reactions were the most frequent local problem: 25% of tesamorelin patients versus 14% on placebo over the first 26 weeks, including redness, itching, pain, irritation and bruising; the label says to rotate sites across the abdomen [3]. Fluid retention (edema, joint pain, carpal tunnel syndrome) is a labeled warning, and the label describes it as transient or resolving when treatment stops [3]. Hypersensitivity reactions occurred in 4%, including itching, redness, flushing, hives and rash, and the label says patients with a suspected reaction should seek prompt medical attention and discontinue [3]. In a 50-patient randomized trial, fasting glucose rose 9 mg/dL versus 2 mg/dL on placebo at 2 weeks and did not differ at 6 months [6].

IGF-1 rises with treatment

Tesamorelin stimulates growth hormone production and raises IGF-1, and the label says to monitor IGF-1 levels during therapy [3]. The label also states that tesamorelin is not indicated for weight loss management because it has a weight-neutral effect [3].

Monitoring points at 26 weeks

Among patients treated for 26 weeks, 47% had IGF-1 above 2 SDS and 36% above 3 SDS; the label says to consider discontinuing for persistent elevations such as above 3 SDS, particularly if the fat-loss response is not robust [3]. The glucose risk is counted at week 26: HbA1c of 6.5% or higher in 5% versus 1% on placebo, hazard ratio about 3.3 (95% CI 1.4 to 9.6). The label says to evaluate glucose before and during therapy and to monitor patients with diabetes at regular intervals for development or worsening of retinopathy [3]. For continuation, the label says to consider the risk and benefit in patients who have not had a reduction in visceral adipose tissue [3].

What 26 and 52 weeks show

The pivotal trials used 2 mg daily of the original 1 mg/vial product. Egrifta SV's 1.4 mg dose was accepted because its exposure is similar to that 2 mg dose [3].

Study 1 gave 412 HIV-infected adults on antiretrovirals 2 mg daily or placebo for 26 weeks. Visceral fat fell 15.2% versus a 5.0% rise; triglycerides fell 50 mg/dL versus a 9 mg/dL rise; IGF-1 rose 81.0% versus a 5.0% fall (P<0.001 for all) [1].

Study 2 randomized 404 patients 2:1. At 6 months, visceral fat fell 10.9% (-21 cm2) with tesamorelin versus 0.6% (-1 cm2) with placebo (P<0.0001), with no change in glucose parameters [2].

Pooled across 806 patients, visceral fat fell 24 cm2 versus a 2 cm2 rise (treatment effect -15.4%), with no significant change in abdominal subcutaneous fat [4]. Patients switched to placebo at week 26 regained visceral fat (about +16% to +22% from week 26 to week 52), while those who continued tesamorelin were at about 0% to -5% [3][5].