Actos reduces type 2 diabetes risk in adults with prediabetes, prior stroke

Issue: July 2016

NEW ORLEANS — The risk for developing type 2 diabetes, especially among those with prediabetes and/or who have had strokes may be reduced with the PPAR agonist Actos, according to a presenter here.

“This is the first time any drug has been shown to both prevent diabetes and also to improve [cardiovascular] outcomes — although these two effects are not necessarily linked,” Silvio E. Inzucchi, MD, director of the Yale Diabetes Center, told Endocrine Today.

Inzucchi and colleagues evaluated data from the Insulin Resistance after Stroke (IRIS) trial on 3,876 people without diabetes who had insulin resistance (defined by homeostasis model of assessment of insulin resistance [HOMA-IR] of more than 3) and who recently had a stroke or heart attack.

Silvio E. Inzucchi

Participants were randomly assigned to Actos (pioglitazone, Takeda; n = 1,939) or placebo (n = 1,937). Researchers sought to determine pioglitazone’s effect on glycemic parameters and diabetes prevention. Diabetes onset was determined by annual interview and fasting plasma glucose testing. Participants’ baseline measures included mean fasting plasma glucose 98.2 mg/dL, HbA1c 5.8%, insulin 22.4 uIU/mL and HOMA-IR 5.4.

HOMA-IR decreased to 4.1 in the pioglitazone group and increased to 5.7 in the placebo group after 1 year (P < .0001); fasting plasma glucose levels were 95.1 mg/dL in the pioglitazone group and 99.7 mg/dL in the placebo group (P < .0001).

Diabetes developed in 3.8% of the pioglitazone group compared with 7.7% of the placebo group during 4.8 years (HR = 0.48; 95% CI, 0.33-0.69).

Participants who had prediabetes (FPG 100 mg/dL or HbA1c 7.5%) and those who had the worst insulin resistance (HOMA-IR 4.6) had the greatest risk reduction for diabetes.

“Pioglitazone is now clearly established as an anti-atherosclerosis medication,” Inzucchi told Endocrine Today. “Our results confirm the hypothesis generated by the PROactive trial 10 years ago, which suggested a beneficial effect on [major adverse cardiac events] in a large group of patients with type 2 diabetes and overt CVD. The diabetes community should take another look at this older, highly cost-effective agent, which had recently fallen into disfavor. Moreover, the stroke community might want to consider whether pioglitazone — perhaps at low doses — might be a new treatment option, in addition, of course, to antiplatelet therapy and blood pressure and lipid management, for patients with cerebrovascular disease who manifest features of insulin resistance.” – by Amber Cox

Reference:

Inzucchi SE, et al. 380-OR. Presented at: American Diabetes Association’s Scientific Sessions; June 10-14, 2016; New Orleans.

Disclosure: Inzucchi reports financial ties with AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Janssen, Lexicon, Merck, Poxel and Sanofi.