Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis.
Level 1 - systematic review of randomized trials
Individual participant data meta-analysis of double-blind randomized controlled trials
PubMed 38554713 · doi:10.1016/S2213-8587(24)00040-8
What was done
Individual participant data meta-analysis of double-blind randomized controlled trials of statin therapy participating in the CTT Collaboration with at least 2 years scheduled duration and at least 1,000 participants. The analysis evaluated 19 trials comparing statin versus placebo (123,940 participants; median follow-up 4.3 years) and 4 trials comparing more- versus less-intensive statin regimens (30,724 participants; median follow-up 4.9 years). Primary outcomes were new-onset diabetes and worsening glycaemia in patients with baseline diabetes, analyzed via standard inverse-variance-weighted meta-analyses.
What was found
Compared with placebo, low- or moderate-intensity statins led to a 10% proportional increase in new-onset diabetes (1.3% vs 1.2% per year; rate ratio [RR] 1.10, 95% CI 1.04-1.16), and high-intensity statins led to a 36% increase (4.8% vs 3.5% per year; RR 1.36, 95% CI 1.25-1.48). Mean blood glucose increased by 0.04 mmol/L with both low/moderate-intensity (95% CI 0.03-0.05) and high-intensity statins (95% CI 0.02-0.06). Mean HbA1c increased by 0.06% (95% CI 0.00-0.12) with low/moderate-intensity and 0.08% (95% CI 0.07-0.09) with high-intensity statins. Approximately 62% of new-onset cases occurred among participants in the top quartile of baseline glycaemia. Among participants with baseline diabetes, the RR for worsening glycaemia was 1.10 (95% CI 1.06-1.14) for low/moderate-intensity and 1.24 (95% CI 1.06-1.44) for high-intensity statins compared with placebo.
Why it matters
The excess in diabetes diagnoses reflects a small, dose-dependent upward shift in glycaemia that tips individuals already close to the diagnostic threshold into clinical diabetes. Any theoretical cardiovascular risk from these small glycaemic increases is already accounted for within the overall net cardiovascular benefit demonstrated by statin trials.
Limits
The reported absolute incidence of new-onset diabetes was heavily dependent on the frequency of follow-up HbA1c testing within individual trials rather than the pharmacological effect alone. The analysis was restricted to trials with at least 1,000 participants and 2 years duration within the CTT Collaboration, and could not address post-trial long-term glycemic trajectory.
Cited by
- partial Statin medications increase insulin resistance and significantly elevate the risk of developing diabetes.