Evidence of Heterogeneity in Statin-Associated Type 2 Diabetes Mellitus Risk: A Meta-Analysis of Randomized Controlled Trials and Observational Studies

Citation

Engeda, Joseph C.; Stackhouse, Ashlyn; White, Mary; Rosamond, Wayne D.; Lhachimi, Stefan K.; Lund, Jennifer L.; Keyserling, Thomas C.; & Avery, Christy L. (2019). Evidence of Heterogeneity in Statin-Associated Type 2 Diabetes Mellitus Risk: A Meta-Analysis of Randomized Controlled Trials and Observational Studies. Diabetes Research and Clinical Practice, 151, 96-105. PMCID: PMC6544490

Abstract

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.

URL

http://dx.doi.org/10.1016/j.diabres.2019.04.005

Reference Type

Journal Article

Year Published

2019

Journal Title

Diabetes Research and Clinical Practice

Author(s)

Engeda, Joseph C.
Stackhouse, Ashlyn
White, Mary
Rosamond, Wayne D.
Lhachimi, Stefan K.
Lund, Jennifer L.
Keyserling, Thomas C.
Avery, Christy L.

PMCID

PMC6544490

ORCiD

Avery - 0000-0002-1044-8162