TOPLINE

Metformin attenuated progressive weight gain in older people with HIV (PWH) who did not have diabetes and obesity compared with placebo, but the benefit reversed once treatment stopped, with weight climbing back towards baseline during the posttreatment follow-up.

METHODOLOGY

• This prespecified secondary analysis of a pilot trial (METFORAGING) evaluated the effects of metformin on weight trajectories in PWH aged 50 years or older.
• Researchers randomly assigned 40 participants (median age, 56.4 years; 30% women) — all virologically suppressed and without diabetes, prediabetes, insulin resistance, or obesity at baseline — to receive either oral metformin or matched placebo for 96 weeks; 35 participants completed treatment through week 96.
• Dosing started at 850 mg once daily and increased to 850 mg twice daily after 4 weeks; participants taking dolutegravir stayed on the once-daily dose due to drug interaction.
• Outcomes were changes from baseline in body weight and BMI at week 96, with reassessment performed at week 144 after treatment was stopped. Serum growth differentiation factor 15 was measured as an exploratory biomarker.
• Additional metabolic outcomes included changes from baseline in fasting plasma glucose, A1c, and fasting insulin levels; insulin resistance; lipids; and waist/hip circumferences at weeks 96 and 144.

TAKEAWAY

• At week 96, participants on metformin lost a mean of 1.5 kg of body weight from baseline, whereas those on placebo had gained 1.3 kg; the between-group difference was -2.8 kg (P = .025); BMI mirrored weight.
• After discontinuation between weeks 96 and 144, participants previously on metformin gained more weight than those on placebo (mean difference, 2.2 kg; P = .045); BMI showed a similar pattern.
• Levels of serum growth differentiation factor 15 rose significantly with metformin and correlated inversely with changes in body weight in that group (correlation coefficient, -0.67; P = .003); no such relationship was seen with placebo.
• No significant between‑group differences were observed in fasting glucose and A1c levels, insulin resistance, lipids, or waist/hip circumference. No serious adverse events were attributed to metformin, and none of the participants discontinued treatment due to metformin‑related adverse events.

IN PRACTICE

"The favourable safety profile over nearly two years supports further evaluation of metformin as a pragmatic, scalable approach to weight management in HIV care," the authors wrote.

SOURCE

The study was led by Cristina Marcelo-Calvo, MD, La Paz University Hospital, Madrid, Spain. It was published online on August 06, 2026, in Open Forum Infectious Diseases.

LIMITATIONS

The trial enrolled a small sample, which reduced precision. Most participants were White and did not have obesity, so the findings may not have applied to broader groups. An imbalance in the distribution of antiretroviral regimens was observed, and participants on dolutegravir received a lower metformin dose, which may have changed the magnitude of the effect.

DISCLOSURES

The trial was funded by the Instituto de Salud Carlos III and co‑funded by the European Union. Several authors disclosed serving as advisory board members or receiving consulting fees, honoraria, meeting support, or research funding from industry, and the corresponding author reported receiving institutional research grants from the study funder.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.