Metformin and weight changes in non-diabetic older people with HIV (METFORAGING): a double-blind, randomised, placebo-controlled, pilot trial

Abstract Background Weight gain is a major complication of contemporary antiretroviral treatment (ART). We evaluated the effects of metformin on weight trajectories and metabolic outcomes in non-diabetic, non-obese, older persons with HIV (PWH). Methods In this double-blind, randomised, placebo-controlled pilot trial (METFORAGING), PWH 50 years or older, virologically suppressed, without diabetes or insulin resistance, were randomly assigned (1:1) to metformin 850 mg or placebo twice daily for 96 weeks at La Paz University Hospital (Madrid, Spain). This prespecified secondary analysis evaluated changes in body weight, body mass index (BMI), glycaemic indices, lipid parameters, and serum growth differentiation factor-15 (GDF-15) in the per-protocol population. Results Forty participants were randomly assigned (metformin n=19; placebo n=21); 35 completed treatment through week 96 (per-protocol population). At week 96, mean weight change was −1.5 kg (95% CI −2.9 to −0.03) with metformin and +1.3 kg (−0.7 to 3.3) with placebo (between-group difference −2.8 kg [95% CI −5.2 to −0.4]; p=.025). After discontinuation, weight in the metformin group returned towards baseline (between-group difference from week 96 to 144: 2.2 kg [95% CI 0.05 to 4.5]; p=.045). At week 96, changes in body weight correlated inversely with changes in serum GDF-15 in the metformin group (r=−0.67; p=.003). No serious adverse events were attributed to metformin. Conclusions Metformin attenuated weight gain in non-diabetic, non-obese PWH receiving contemporary ART, but the effect was not sustained after discontinuation. These findings support larger trials to confirm efficacy and define optimal treatment duration. Trial Registration. EudraCT 2021-003299-15.