Pioglitazone treatment and cardiovascular event and death in subjects with type 2 diabetes without established cardiovascular disease (JDDM 36)

Diabetes Res Clin Pract. 2015 Sep;109(3):485-92. doi: 10.1016/j.diabres.2015.06.005. Epub 2015 Jul 16.

Abstract

Aims: The protective association of pioglitazone with cardiovascular events and death was investigated over 6-years in large-scale type 2 diabetic subjects without established cardiovascular disease in a primary care setting.

Methods: A six-year observational cohort study including 2864 subjects with type 2 diabetes without established cardiovascular disease was performed. The primary endpoint was a composite of first occurrence of cardiovascular disease or death. The effect of pioglitazone use at a baseline year with a Cox proportional hazard model and the time-dependent use in each one-year examination interval with a pooled logistic regression model were analyzed.

Results: Baseline use of pioglitazone (n=493) did not show a statistically protective effect on the primary endpoint (n=175), although it tended to reduce the risk (adjusted hazard ratio 0.67 [95% CI: 0.43-1.05]). However, pooled logistic regression analysis indicated a significant protective association of pioglitazone with the primary endpoint (0.58 [0.38 to 0.87] and cardiovascular disease (0.54 [0.33-0.88]), independent of concurrent levels of blood glucose, blood pressure, lipids, albuminuria, and renal function. In particular, this protective association was observed in those with diabetic nephropathy regardless of the daily dose of pioglitazone. Among a total of 898 subjects who took pioglitazone during the period, 43% experienced a discontinuation at least once; however, serious adverse effects were rare.

Conclusions: This observational study indicated a protective association of pioglitazone with cardiovascular disease and death in type 2 diabetic subjects without established vascular disease, particularly those with nephropathy.

Keywords: Pioglitazone; cardiovascular disease; coronary heart disease; mortality; observational cohort; stroke; type 2 diabetes.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria / blood
  • Albuminuria / complications
  • Albuminuria / epidemiology
  • Albuminuria / mortality
  • Blood Glucose / drug effects
  • Blood Glucose / physiology
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / mortality
  • Cause of Death
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / epidemiology
  • Diabetic Nephropathies / mortality
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Pioglitazone
  • Thiazolidinediones / therapeutic use*

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Thiazolidinediones
  • Pioglitazone