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Is there sufficient evidence for a causal association between antiretroviral therapy and diabetes in HIV‐infected patients? A meta‐analysis

The association of antiretroviral therapy (ART) with diabetes is inconsistent and varies widely across primary epidemiological studies. A comprehensive and more precise estimate of this association is fundamental to establishing a plausible causal link between ART and diabetes. We identified epidemiological studies that compared mean fasting plasma glucose (FPG) concentrations and proportions of diabetes and metabolic syndrome between HIV‐infected patients naïve and exposed to ART. Mean difference in FPG concentrations and odds ratios of diabetes and metabolic syndrome were pooled using random‐effects meta‐analyses. Data on 20 178 participants from 41 observational studies were included in the meta‐analyses. Mean FPG concentrations (Pooled mean difference: 4.66 mg/dL; 95% confidence interval [CI], 2.52 to 6.80; 24 studies) and the odds of diabetes (Pooled odds ratios: 3.85; 95% CI, 2.93 to 5.07; 10 studies) and metabolic syndrome (Pooled odds ratios: 1.45; 95% CI, 1.03 to 2.03; 18 studies) were significantly higher among ART‐exposed patients, compared to their naïve counterparts. ART was also associated with significant increases in FPG levels in studies with mean ART duration ≥18 months (Pooled mean difference: 4.97 mg/dL; 95% CI, 3.10 to 6.84; 14 studies), but not in studies with mean ART duration <18 months (Pooled mean difference: 4.40 mg/dL, 95% CI, –0.59 to 9.38; 7 studies). ART may potentially be the single most consistent determinant of diabetes in people living with HIV worldwide. However, given the preponderance of cross‐sectional studies in the meta‐analysis, the association between ART and diabetes cannot be interpreted as cause and effect.