Pioglitazone Exposure Reduced the Risk of All-Cause Mortality in Insulin-Treated Patients with Type 2 Diabetes Mellitus

Abstract

Context The long-term safety and benefit of pioglitazone use in combination with insulin are still uncertain. Objective This study compared the risks of all-cause mortality and major cardiovascular (CV) events between pioglitazone users and nonusers receiving insulin therapy. Design, Setting and Patients We conducted a 13-year retrospective cohort study by using data from the population-based National Health Insurance Research Database in Taiwan. A total of 20 376 patients with type 2 diabetes mellitus (T2DM) receiving insulin therapy were enrolled during 2000 to 2012. Overall, the incidence rates of all-cause mortality and CV events were compared between 2579 pioglitazone users and 2579 matched nonusers. Results After adjustment for age, sex, comorbidities, Diabetes Complications Severity Index scores, and drugs used, mortality rates were 30.26 and 15.02 per 1000 person-years for pioglitazone nonusers and users, respectively. The adjusted hazard ratio (aHR) of mortality was 0.47 (95% confidence interval [CI]: 0.38–0.58, P < 0.001) for pioglitazone users compared with nonusers. The aHRs of CV and non-CV deaths were 0.78 (95% CI: 0.51–1.19) and 0.50 (95% CI: 0.38–0.66), respectively. The aHRs of hospitalized coronary artery disease, hospitalized stroke, and incident heart failure were not significantly different between pioglitazone users and nonusers. Conclusions This nationwide cohort study demonstrated that pioglitazone use reduced the risks of all-cause mortality and non-CV death for patients with T2DM undergoing insulin therapy.

Pioglitazone for primary stroke prevention in Asian patients with type 2 diabetes and cardiovascular risk factors: a retrospective study

“…Data from these studies provide strong evidence to support the use of pioglitazone for secondary stroke prevention, and it is possible that the results could be extended in the future to populations without a history of stroke [13]. Based on real-world data, the effect of pioglitazone on stroke varies according to the different clinical characteristics of patients and the interaction with other glucose-lowering agents [14][15][16][17][18]. A meta-analysis of randomized-controlled trials (RCTs) revealed that pioglitazone reduced the risk of stroke in patients with a history of established cardiovascular (CV) diseases [19].…”

Endocrine disruptor chemicals as obesogen and diabetogen: Clinical and mechanistic evidence

“…M1 macrophage infiltration accompanies whitening of brown fat, suggestive of BAT dysfunction (Figure 2 ). Some phytochemicals and phthalates also can promote M2 macrophage polarization and beiging in WAT[ 111 , 112 ].…”

Practical use of insulin degludec/insulin aspart in a multinational setting: beyond the guidelines

“…53 In addition, recent data showed that pioglitazone in combination with insulin may reduce the risks of all-cause mortality and non-cardiovascular death in people with T2D. 54 No additional considerations are required when combining…”

“…However, a recent systematic review suggested that pioglitazone is a feasible adjunct to insulin therapy 53 . In addition, recent data showed that pioglitazone in combination with insulin may reduce the risks of all‐cause mortality and non‐cardiovascular death in people with T2D 54 …”