Joseph C Engeda1, Ashlyn Stackhouse2, Mary White3, Wayne D Rosamond2, Stefan K Lhachimi4, Jennifer L Lund2, Thomas C Keyserling5, Christy L Avery2. 1. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, United States. Electronic address: engeda@email.unc.edu. 2. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. 3. School of Information and Library Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. 4. Research Group Evidence-Based Public Health, Leibniz Institute for Epidemiology and Prevention Research (BIPS), Bremen, Germany; Health Sciences Bremen, Institute for Public Health and Nursing, University of Bremen, Bremen, Germany. 5. Division of General Medicine and Clinical Epidemiology, University of North Carolina, Chapel Hill, NC, United States; Center for Health Promotion and Disease Prevention, University of North Carolina, Chapel Hill, NC, United States.
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.
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.
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