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Statin therapy increases risk for incident diabetes in high-risk adults
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Adults with prediabetes who participated in the Diabetes Prevention Program Outcomes Study were more likely to develop incident type 2 diabetes if they initiated statin therapy before diagnosis, according to an analysis published in BMJ Open Diabetes Research & Care.
Statin therapy may offer health benefits that extend beyond its lipid-lowering properties, including favorable effects on systemic inflammation, endothelial function and oxidative stress, all of which are involved in the etiology of cardiometabolic diseases, Jill P. Crandall, MD, professor of clinical medicine at Albert Einstein College of Medicine in Bronx, New York, and colleagues wrote in the study background.
“These effects might be predicted to reduce diabetes risk; instead, accumulating evidence suggests that the use of statins may increase the risk for developing type 2 diabetes,” Crandall and colleagues wrote. “Following an initial publication reporting this observation, meta-analyses of randomized clinical trials of lipid-lowering with statins have confirmed this effect, and suggest that statin treatment is associated with a small increase, approximately 10% to 12%, in the risk for incident diabetes compared with placebo, although not all such analyses find increases in diabetes risk.”
Crandall and colleagues analyzed data from 3,234 adults with prediabetes participating in the Diabetes Prevention Program Outcomes Study, a long-term follow-up to a randomized clinical trial of interventions (metformin therapy, lifestyle intervention or usual care) to prevent type 2 diabetes. Researchers assessed incident diabetes with an annual 75-g oral glucose tolerance test and semiannual fasting blood glucose; lipid profile was measured annually. Decisions regarding the initiation of statin therapy were made by the participant’s physician outside of the study protocol. Statin use was assessed at baseline and semiannual visits via patient self-report. Researchers used Cox proportional hazards models to assess the time-dependent association between statin use and diabetes-onset risk.
At 10 years, cumulative incidence of statin initiation before a diabetes diagnosis was 35% in the usual care group, 37% in the metformin group and 33% in the lifestyle intervention group. The most commonly used statins were simvastatin (40%) and atorvastatin (37%), with statin use increasing substantially after a diabetes diagnosis, according to researchers.
Across the usual care, metformin and lifestyle intervention groups, researchers observed a greater risk for developing incident type 2 diabetes among those prescribed statin therapy before diagnosis. The pooled HR for risk with statin therapy among all three treatment groups was 1.36 (95% CI, 1.17-1.59), with no interaction observed between sex and statin use on diabetes risk.
Researchers also observed that a longer duration of statin use was associated with greater diabetes risk in the lifestyle intervention group (HR per visit with statin use = 1.06; 95% CI, 1.02-1.11). Diabetes risk did not differ with low vs. high-potency statins, according to researchers, and risk was not materially altered by adjustment for baseline diabetes risk factors and potential confounders related to indications for statin therapy.
“For individual patients, a potential, modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke and cardiovascular death associated with statin treatment,” the researchers wrote. “Nonetheless, glucose status should be monitored and healthy lifestyle behaviors reinforced in high-risk patients who are prescribed statins for CVD prophylaxis.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.
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