Pioglitazone May Reduce Overall Mortality Risk in Patients With Type 2 Diabetes

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Findings showed that the combination of insulin and pioglitazone lowered all-cause mortality risk, and this combination therapy exerted beneficial effects on noncardiovascular deaths.

Pioglitazone in combination with insulin therapy reduces the risk for mortality and noncardiovascular death in patients with type 2 diabetes, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

The oral antidiabetic drug pioglitazone has been shown to improve glycemic control in insulin-treated patients with type 2 diabetes, but the long-term safety and benefits have not been evaluated. Researchers sought to characterize the risk for all-cause mortality and cardiovascular events in pioglitazone users and nonusers in patients with type 2 diabetes from the National Health Insurance Research Database in Taiwan.

A total of 2579 patients (47.23% women) with type 2 diabetes who were treated with pioglitazone were included in the retrospective study, along with 2579 matched comparators (nonusers). Patient information was collected from the Longitudinal Health Insurance Database 2000. The primary outcome of the study was all-cause mortality, including rates of cardiovascular-related death and noncardiovascular-related death. Incidence rates of cardiovascular events, including heart failure, hospitalization, and stroke, were also examined.

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The all-cause mortality rate among pioglitazone users was 15.02 per 1000 person-years. This was significantly lower than the mortality rate among nonusers, which was 30.26 per 1000 person years (adjusted hazard ratio, 0.47; 95% CI, 0.38-0.58; P <.001). This was primarily driven by differences in the rates of noncardiovascular death for users and nonusers, which were 9.11 and 19.74 per 1000 person-years, respectively (adjusted hazard ratio, 0.50; 95% CI, 0.38-0.66; P <.001). There was no significant difference in the rates of and risk for cardiovascular death or events between pioglitazone users and nonusers.

The authors noted that the use of administrative data for analysis represented a limitation of the study, as insulin and pioglitazone dosage and adherence could not be confirmed.

“[O]ur study demonstrated that the combination of insulin and pioglitazone lowered the all-cause mortality risk,” the researchers concluded. “Pioglitazone might be a beneficial complementary agent for insulin treatment. Additional studies are needed to establish its optimal application in real-world practice.”

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Yen FS, Wang HC, Pan CW, Wei JC, Hsu CC, Hwu CM. Pioglitazone exposure reduced the risk of all-cause mortality in insulin-treated patients with type 2 diabetes mellitus [published online September 23, 2019]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgz026