RESUMEN
Background Diabetes mellitus (DM) and human immunodeficiency virus (HIV) itself increase the risk for cardiovascular diseases in people living with HIV (PLHIV). Prediabetes, a condition preceding DM, is common in PLHIV receiving antiretroviral therapy (ART). Both metformin and lifestyle interventions have been established to reduce the risk of progression from prediabetes to DM in the general population. This study aimed to evaluate the efficacy of metformin for preventing DM in prediabetic PLHIV. Methods An open-label randomized controlled clinical trial was conducted in HIV-positive persons with prediabetes. The participants were randomized into two groups: the metformin group (received metformin) and the control group (did not receive metformin). All participants were counseled regarding diet control and lifestyle modification and followed for 12 months. The primary endpoint was the development of DM. Fasting plasma glucose (FPG), two-hour plasma glucose (2-h PG) after 75 g oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), and computer-based homeostatic model assessment index of beta-cell function (HOMA%B) and insulin resistance (HOMA-IR) were analyzed. Results Seventy-four participants were enrolled, 37 in each group. The mean age was 49.6 years, and 68.9% were males. At baseline, the mean CD4 cell count was 570 cells/mm3, and the mean body mass index (BMI) was 24.6 kg/m2. Baseline characteristics including age, sex, BMI, waist/hip ratio, duration of ART, ART regimen, CD4 cell count, and HIV RNA were similar between the two groups. The mean FPG, 2-h PG, HbA1c, HOMA%B, and HOMA-IR at baseline were also similar between the two groups. At 12 months, one participant in the metformin group and three in the control group developed DM (risk reduction: 5.41%; 95% confidence interval (CI): -6.92%-18.78%). When we compared changes in parameters between the two groups, there were trends toward more changes in HbA1c ([Formula: see text]HbA1c) at both six months (metformin group versus control group: -0.17% ± 0.20% versus 0.02% ± 0.58%; p = 0.074) and 12 months (metformin group versus control group: -0.05% ± 0.23% versus 0.06% ± 0.27%; p = 0.065). When we considered changes in all parameters in each group, the metformin group had significant reductions in body weight (BW) and BMI at both six and 12 months, and significant reductions in HbA1c and HOMA-IR at six months. No participant had adverse effects that led to the discontinuation of metformin. No cardiovascular event was observed during the study period. Conclusions Metformin tends to improve HbA1c and insulin resistance and may prevent progression from prediabetes to DM in HIV-positive persons with prediabetes. A further large study with a longer study period is needed to evaluate the long-term benefit of metformin.