Pioglitazone greatly decreases the risk of developing type 2 diabetes, especially for those who already have prediabetes and/or who have had strokes, according to a study presented at the American Diabetes Association’s 76th Scientific Sessions® at the Ernest N. Morial Convention Center in New Orleans.
The Insulin Resistance Intervention after Stroke trial (IRIS) recently found that the thiazolidinedione (TZD) drug, pioglitazone, reduced the risk of fatal and non-fatal stroke and myocardial infarction (heart attack) by 24 percent, in people with cerebrovascular disease—a group of conditions that affects the flow of blood to the brain. This secondary analysis of the data collected in the IRIS trial examined pioglitazone’s effect on diabetes prevention in a large group of non-diabetic stroke patients with insulin resistance, including many people who had prediabetes. The analysis found that pioglitazone reduced progression to diabetes by 52 percent.
“While previous studies have shown that TZD medications can reduce diabetes risk, this is the first to show they can do so in a group of patients with established cardiovascular disease. It’s also the first time a glucose-lowering drug has been shown to both reduce diabetes and also reduce the risk of cardiovascular complications in the same study,” said lead investigator Silvio E. Inzucchi, MD, Director of the Yale Diabetes Center.
“Insulin resistance is very common after stroke,” he said. “Treating insulin resistance with pioglitazone cuts the risk of diabetes in half, while also reducing the risk of stroke and heart attack by one-quarter. This is a potentially powerful dual effect to combat metabolic and cardiovascular disease.”
The IRIS trial included 3,876 patients who recently had a stroke or heart attack, insulin resistance (defined as Homeostasis Model Assessment of Insulin Resistance >3.0) and who did not have diabetes (defined as no prior history and fasting plasma glucose of <126 mg/dl). They were randomly assigned to pioglitazone (45 mg QD) (n=1,939) or placebo (n=1,937). At baseline, patients exhibited mean fasting plasma glucose levels (FPG) of 98.2 mg/dl, A1C of 5.8 percent and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) of 5.4. They were assessed annually through interviews and FPG testing. After the first year, mean HOMA-IR dropped to 4.1 in the pioglitazone group and increased to 5.7 in the placebo group (p<0.0001), while FPG decreased to 95.1 mg/dl in the pioglitazone group and increased to 99.7 mg/dl in the placebo group (p<0.0001).During 4.8 years of follow up, 73 (3.8 percent) patients in the pioglitazone group developed type 2 diabetes, compared to 149 (7.7 percent) in the placebo group (HR 0.48; 95% CI 0.33, 0.69; p<0.0001).
The greatest reduction in risk occurred in patients who had prediabetes (FPG greater than or equal to 100 mg/dl, or A1C greater than or equal to 5.7 percent) and those who had the worst insulin resistance (HOMA-IR greater than or equal to 4.6). For those two groups of patients, absolute risk reduction (ARR) was 8.5 percent, compared to 0.8 percent (for those with FPG less than 100 mg/dl); 5.6 percent, compared to 1 percent (for those with A1C less than 5.7 percent); and 6.3 percent, compared to 1.4 percent (for those with HOMA-IR less than 4.6), respectively.
 Kernan WN, Viscoli CM, Furie, KL, et al. Pioglitazone after ischemic stroke or transient ischemic attack.N Engl J Med 2016; 374:1321-1331