Add-On Pioglitazone and Sulfonylureas Safe, Effective for Poorly Controlled Diabetes

Both pioglitazone and sulfonylureas were effective add-on treatments for the prevention of cardiovascular events among patients with poorly controlled type 2 diabetes taking metformin, according to the findings of a recent study.

The randomized clinical trial included 3028 patients aged 50 to 75 years with inadequately controlled type 2 diabetes despite receiving metformin monotherapy. Patients were randomly assigned to receive 15 to 45 mg of pioglitazone (n=1535) or a sulfonylurea (n=1493): 5 to 15 mg of glibenclamide (24 [2%]), 2 to 6 mg of glimepiride (723 [48%]), or 30 to 120 mg of gliclazide (745 [50%]). A total of 335 patients (11%) had experienced a previous cardiovascular event at baseline. The primary outcome was a composite of the first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularization.

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Overall, the primary outcome occurred in 105 patients who received pioglitazone and in 108 patients who received sulfonylureas, with an incidence rate of 1.5 per 100 person-years for both groups and hazard ratio of 0.96.

Hypoglycemia occurred in fewer patients in the pioglitazone group compared with patients in the sulfonylureas group (148 [10%] vs 508 [34%], respectively). However, rates of heart failure, bladder cancer, and fractures were not significantly different between groups. In addition, moderate weight gain occurred in both groups, which was less than 2 kg, on average.

After a median 57.3 months of follow-up, the researchers stopped the study based on findings from a futility analysis.

“In this long-term, pragmatic trial, incidence of cardiovascular events was similar with sulfonylureas (mostly glimepiride and gliclazide) and pioglitazone as add-on treatments to metformin,” the researchers concluded. “Both of these widely available and affordable treatments are suitable options with respect to efficacy and adverse events, although pioglitazone was associated with fewer hypoglycaemia events.”

—Melissa Weiss

Reference:

Vaccaro O, Masulli M, Nicolucci A, et al. Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial [published online September 13, 2017]. Lancet Diabet & Endocrinol. http://dx.doi.org/10.1016/S2213-8587(17)30317-0.