Evidence of heterogeneity in statin-associated type 2 diabetes mellitus risk: a meta-analysis of randomized controlled trials and observational studies.

AIMS: To conduct a meta-analysis of statin-associated type 2 diabetes mellitus (T2D) risk among randomized controlled trials (RCTs) and observational studies (OBSs), excluding studies conducted among secondary prevention populations.

METHODS: Studies were identified by searching PubMed (1994-present) and EMBASE (1994-present). Articles had to meet the following criteria: 1) follow-up >one year; 2) >50% of participants free of clinically diagnosed ASCVD; 3) adult participants ≥30 years old; 4) reported statin-associated T2D effect estimates; and 5) quantified precision using 95% confidence interval. Data were pooled using random-effects model.

RESULTS: We identified 23 studies (35% RCTs) of n=4,012,555 participants. OBS participants were on average younger (mean difference= 6.2 years) and had lower mean low-density lipoprotein cholesterol (LDL-C, mean difference=20.6 mg/dL) and mean fasting plasma glucose (mean difference=5.2 mg/dL) compared to RCT participants. There was little evidence for publication bias (P>0.1). However, evidence of heterogeneity was observed overall and among OBSs and RCTs (PCochran =<0.05). OBS designs, younger baseline mean ages, lower LDL-C concentrations, and high proportions of never or former smokers were significantly associated with increased statin-associated T2D risk.

CONCLUSIONS: Potentially elevated statin-associated T2D risk in younger populations with lower LDL-C merits further investigation in light of evolving statin guidelines targeting primary prevention populations.