Pioglitazone tested for diabetes prevention

Jim Kling

March 28, 2011

San Antonio, TX - Pioglitazone (Actos, Takeda) therapy led to a 72% reduction in the conversion rate from impaired glucose tolerance to type 2 diabetes mellitus, but adverse effects included weight gain and edema, according to a study published in the March 24, 2011 issue of the New England Journal of Medicine[1].

Hyperglycemia contributes to microvascular and macrovascular complications of diabetes, suggesting that preventing or delaying hyperglycemia could lead to reductions in long-term complications, Dr Ralph A DeFronzo (Texas Diabetes Institute and University of Texas Health Science Center, San Antonio) and colleagues explain. Previous studies showed that reduction in conversion of impaired glucose tolerance to type 2 diabetes can be achieved through lifestyle modification, bariatric surgery, or the use of metformin, thiazolidinediones, or acarbose (Precose, Bayer Pharmaceuticals).

In the Actos Now for Prevention of Diabetes (ACT NOW) study, a randomized, double-blind, placebo-controlled study in 602 adults who received pioglitazone or placebo, the researchers investigated whether pioglitazone could reduce the risk of type 2 diabetes in subjects with impaired glucose tolerance.

Over a median follow-up of 2.4 years, 2.1% of patients on pioglitazone converted to type 2 diabetes, compared with 7.6% of the placebo group (72% reduction; hazard ratio for conversion to type 2 diabetes in pioglitazone group 0.28; p<0.001]). In addition, 48% of patients on pioglitazone converted to normal glucose levels, compared with 28% in the placebo group (p<0.001). Pioglitazone treatment was also associated with reduced levels of fasting glucose compared with placebo (a decrease of 11.7 mg/dL vs 8.1 mg/dL, p<0.001), as well as two-hour glucose (a decrease of 30.5 mg/dL vs 15.6 mg/dL, p<0.001), and HbA1c (a decrease of 0.04% vs an increase of 0.20%, p<0.001).

Patients on pioglitazone also had a decrease in diastolic blood pressure (-2.0 mm Hg vs 0.0 mm Hg; p=0.03), a reduction in carotid intima-media thickening (31.5%; p=0.047), and a bigger increase in the level of high-density lipoprotein cholesterol (7.35 mg/dL vs 4.5 mg/dL; p=0.008).

Those receiving pioglitazone gained more weight than the placebo group (3.9 kg vs 0.77 kg, p<0.001) and had higher rates of edema (12.9% vs 6.4%, p=0.007).

Commenting on the study, Dr Timothy S Harlan (Tulane University Medical Group, New Orleans, LA) was lukewarm about the paper's conclusions. "I don't know that these data are earth-shattering. We know these medications control HbA1c quite well, but the problem is that they often do so at the expense of weight gain and edema."

Harlan said that the data from the study suggest that pioglitazone is safer than other drugs in the class, but he isn't entirely convinced. "I have prescribed [pioglitazone], and I do it very carefully, as a third-line therapy. At this stage, I don't think I would prescribe this to prevent diabetes in my patients. I'd like to see a lot more data before I widely prescribe it."

Instead, he favors more emphasis on diet and exercise. "Insurance companies will willingly reimburse for medicines like this, yet we will not invest that same level in helping people do what works better, and that's lifestyle changes."

The study was supported by a grant from Takeda Pharmaceuticals . DeFronzo reports receiving payments for board membership from Amylin, Takeda, ISIS, and Boehringer Ingelheim and reports that the University of Texas Health Science Center at San Antonio has received grant support from Takeda, Amylin, and Eli Lill y . D isclosures for the coauthors are listed in the paper. Harlan reports no conflicts of interest.

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