Statins tied to higher risk of diabetes progression

Statin therapy is associated with an excess risk of diabetes progression, including increased likelihood of poor glycaemic control, need for treatment escalation, and hyperglycaemic complications, a cohort study has found.

“This statin-associated metabolic cost was not measured by RCTs, which instead focused mainly on cardiovascular [CV] benefits,” the researchers pointed out. “The higher risk of diabetes progression associated with statin use may seem less consequential, at least in the short and intermediate term, than the CV benefits of statin use, especially when used for secondary prevention.” 

“However, diabetes progression has long-term effects on quality of life and treatment burden, which warrant consideration when discussing the overall risk-benefit profile, especially when used for primary prevention,” they highlighted.

The retrospective study involved 83,022 pairs of statin users matched to active comparators (mean age 60.1 years, 94.9 percent men). Active comparators consisted of patients who initiated treatment with a H2-blocker or proton pump inhibitor but not concurrently prescribed a statin. All participants were regular users of the US Veterans Affairs health system aged ≥30 years, who had been diagnosed with diabetes within the study period.

Diabetes progression was defined by a composite of incident insulin initiation, increased classes of glucose-lowering medication used, hyperglycaemia (blood glucose of ≥200mg/dL), or incident ketoacidosis or uncontrolled diabetes. [JAMA Intern Med 2021;doi:10.1001/jamainternmed.2021.5714]

Compared with active comparators, people who took statins were significantly more likely to experience the composite outcome of diabetes progression (55.9 percent vs 48.0 percent; odds ratio [OR], 1.37; p<0.001).

Each component of the composite outcome also occurred more commonly among statin users than the active comparators.  Statin users were more likely to require escalation of diabetes treatment, including initiation of insulin therapy (OR, 1.16; p<0.001) and to use more number of glucose-lowering medication classes (OR, 1.41; p<0.001).

“This escalation of diabetes treatment was associated with worse diabetes control, including new persistent hyperglycaemia [OR, 1.13] and acute glycaemic complications [OR, 1.24],” noted the researchers.

In addition, the higher intensity of LDL lowering with statin, the greater the likelihood of diabetes progression — indicating a dose-response relationship between statin use and diabetes progression. The ORs for diabetes progression in statin users vs nonusers grew from 1.45 to 1.55 and 1.83 for low-, moderate-, and high-intensity cholesterol lowering, respectively.

“The number needed to be exposed to statins for one additional person to experience diabetes progression outcome was 13,” the researchers reported.

“The risk-benefit ratio of statin use in patients with diabetes should take into consideration its metabolic affects,” they added. “Further research is needed to form a risk-tailored approach to balancing the CV benefits of statin therapy with its risk of diabetes progression.”