This article is more than 5 years old. Information may no longer be current.
Study: Pioglitazone halts progression to type 2 diabetes
DeFronzo RA. N Engl J Med. 2011;364:1104-1115.
Click Here to Manage Email Alerts
In a new study, pioglitazone reduced the risk for progression from impaired glucose tolerance to type 2 diabetes by 72% as compared with placebo. However, the drug was linked to significant edema and weight gain.
Ralph A. DeFronzo, MD, and colleagues recruited 602 adults with IGT to study whether pioglitazone (Actos, Takeda) could reduce the risk for type 2 diabetes. Patients were randomly assigned to pioglitazone, at 30 mg per day and increased to 45 mg per day after 1 month, or placebo for a mean 2.4 years.
After follow-up, the pioglitazone group had an annual incidence rate for type 2 diabetes of 2.1% vs. the placebo group’s 7.6%. The researchers calculated a hazard ratio for conversion to diabetes in the pioglitazone group of 0.28 (95% CI, 0.16-0.49). According to the researchers, the decreased rate of conversion to diabetes was “slightly larger than that observed with other thiazolidinediones (52% to 62%) and lifestyle modification (58%).”
Nearly half (48%) of the pioglitazone group converted from IFG to normal glucose tolerance compared with 28% of the placebo group (P<.001). In addition, compared with placebo, pioglitazone significantly reduced levels of fasting glucose (11.7 mg/dL vs. 8.1 mg/dL), 2-hour glucose (30.5 mg/dL vs. 15.6 mg/dL) and HbA1c (–0.04% vs. 0.2%).
Other positive findings associated with pioglitazone therapy included decreased diastolic blood pressure (20 mm Hg vs. 0 mm Hg), reduced carotid intima-media thickening rate (31.5%), increased HDL levels (7.35 mg/dL vs. 4.5 mg/dL) and improved serum levels of alanine aminotransferase and aspartate aminotransferase.
The number of patients lost to follow-up was “relatively high” in both groups; 90 patients assigned to pioglitazone and 71 assigned to placebo dropped out of the study.
Weight gain — one reason for withdrawal in both groups — was greater in patients assigned to pioglitazone (3.9 kg vs. 0.77 kg; P<.001). However, “the greater the weight gain, the greater the improvements in beta-cell function and insulin sensitivity and, thus, the greater the reduction in HbA1c,” the researchers wrote in the study. Edema was also more frequent in the pioglitazone group (12.9% vs. 6.4%; P=.007).
The incidence of fracture, which has been implicated as a cause for concern with the TZD drug class, was similar in both groups; all were related to trauma.
The researchers concluded that “treatment of 18 participants for 1 year prevented one case of diabetes. The influence of these effects on long-term diabetic complications remains to be determined.”
Disclosure: The study was supported by Takeda Pharmaceuticals. The researchers report various relevant financial disclosures; read the full study for details.
The 72% reduction in incident type 2 diabetes in the pioglitazone-treated group of high-risk patients is impressive, but the trade-off of weight gain and edema in a significant number certainly reduces my enthusiasm for recommending pioglitazone to such patients. I think it is interesting that even when this drug is used as stand-alone therapy in 'healthier' patients, weight gain and edema are problematic.
– Stephen A. Brietzke, MD
Endocrine Today Editorial Board member
Disclosure: Dr. Brietzke reports no relevant financial disclosures.
 |
Follow EndocrineToday.com on Twitter. |