Weekly Journal Scan: A reassuring answer to questions about statin therapy and diabetes

Key Points• In this meta-analysis of individual participant data from 23 double-blind, randomized controlled trials (RCTs) participating in the Cholesterol Treatment Trialists' (CTT) Collaboration, the authors sought to investigate the effects of statin therapy allocation on new-onset diabetes and on worsening glycaemia in patients with diabetes.• Eligibility criteria for RCTs were as follows: (i) no protocol-mandated differences between treatment groups other than those created by allocation to receive statin and its comparator (placebo or a statin with different intensity); (ii) at least 1000 patients enrolled; and (iii) a mean scheduled follow-up of at least 2 years.• Baseline diabetes was defined as a recorded history of diabetes or diabetes-related adverse event, use of glucose-lowering medications, fasting plasma glucose concentration ≥7 mmol/L, random plasma glucose ≥11.1 mmol/L, or glycated haemoglobin (HbA1c) value ≥6.5% on or before the date of participant assignment to a treatment group.New-onset diabetes was defined with the above-mentioned characteristics recorded after participant assignment to a treatment group.Worsening glycaemia was defined as any adverse event relating to ketosis or glucose control, HbA1c increase from baseline of ≥0.5%, or escalation of glucose-lowering medications after participant assignment to a treatment group.• Of the included RCTs, 19 compared any statin regimen with placebo, with 123 940 participants, a median follow-up of 4 years, and 25 701 subjects (21%) with a history of diabetes or meeting the prespecified definition of baseline diabetes.In the analysis of the RCTs comparing low-or moderate-intensity statin vs. placebo (n = 14), the allocation to statin treatment resulted in a 10% increase in new-onset diabetes [2420 of 39 179 participants in the statin group vs. 2214 of 39 266 participants assigned to placebo; relative risk (RR), 1.10; 95% confidence interval (CI), 1.04-1.16],corresponding to an incidence of 1.3% per year compared to 1.2% in the placebo group, with a mean absolute excess of 0.12% during each year of treatment.Those treated with a high-intensity statin (two RCTs) had a larger, 36% proportional increase in newonset diabetes (1221 of 9935 participants in the statin group vs. 905 of 9859 participants assigned to placebo; RR, 1.36; 95% CI, 1.25-1.48),with rates of 4.8% vs. 3.5% per year and an absolute annual excess of 1.27%.Of note, in the high-intensity statin trials, HbA1c and glucose levels were measured in 72% and 49% of participants without diabetes at baseline vs. 3% and 37% of those in the low-or moderate-intensity statin trials.• In the 4 RCTs comparing more vs.less intensive statin therapy (30 724 participants, 17% with diabetes, median follow-up of 5 years), highintensity regimens resulted in a 10% increase in newly diagnosed diabetes (RR, 1.10; 95% CI, 1.02-1.18).For a given level of statin intensity, the results were consistent among participant subgroups (e.g. by age, sex, race, and body mass index) and did not vary over time.Among patients without diabetes at baseline, the mean increase in glucose concentration compared with placebo was 0.04 mmol/L for both low-or moderateintensity and high-intensity statin therapy, and the increases in HbA1c values were 0.06% for low-or moderate-intensity and 0.08% for highintensity statin therapy.Up to 62% of new-onset diabetes occurred among participants in the highest quartiles of glycaemia distribution.• In those with pre-existing diabetes, low-or moderate-intensity statins resulted in a 10% relative increased risk of worsening glycaemia compared with placebo (RR, 1.10; 95% CI, 1.06-1.14;absolute annual excess 1.49%), and high-intensity statins resulted in a 24% relative worsening of glycaemia compared with placebo (RR, 1.24; 95% CI, 1.06-1.44;absolute annual excess 3.02%).The mean increase in glucose concentration compared with placebo was 0.12 mmol/L for low-or moderate-intensity statin therapy and 0.22 mmol/L for high-intensity statin therapy, with a corresponding increase in HbA1c values of 0.09% for low-or moderate-intensity and 0.24% for high-intensity statin therapy.