Water Retention With Pioglitazone Causes Weight Gain

Up to 75 percent of the increase in body weight that can occur in patients with type 2 diabetes who are treated with pioglitazone is from water retention but the drug also tends to reduce abdominal fat and blood pressure.

Dr. Ananda Basu and colleagues at the Mayo Clinic Rochester, Minnesota compared the effects of pioglitazone, sold under the trade name Actos, and glipizide, sold in the US under the trade name Metaglip, on body composition and body water content, as well as other factors, in 19 patients with type 2 diabetes.

The researchers randomly assigned the subjects to 45 mg/d of pioglitazone or glipizide, which was increased up to a maximum of 20 mg/d (average dose was 10 mg/d) for a period of 12 weeks. The degree of glucose control "was essentially equivalent" with both drugs, the investigators report.

Pioglitazone caused an average increase in total body water of 2.4 L. This accounted for 75 percent of the patients’ average weight gain of 3.1 kg. There was no change in total body water content with glipizide.

Basu’s group also measured the patients’ accumulation of total abdominal and visceral fat — fat deposits surrounding the internal organs associated with an increased risk of cardiovascular disease. With pioglitazone, the researchers recorded decreases of 32 and 16 cubic centimeters in total abdominal and visceral fat, respectively. With glipizide, fat levels increased by 38 and 18 cubic centimeters, respectively.

Pioglitazone also tended to reduce the average blood pressure, but glipizide had no impact on blood pressure.
In conclusion, "pioglitazone’s effect on body water content is more substantial than had been previously thought," stated Dr. Basu. Therefore, caution should be exercised in patients with heart or kidney problems.
Diabetes Care, March 2006.

================================

DID YOU KNOW:
Intensive Treatment Reduces CVD Risk: Patients with diabetes have two- to four-fold increased risk of cardiovascular disease and have higher mortality risk than the general population. Reducing high blood pressure and cholesterol have shown to be beneficial to patients with diabetes. The UKPDS showed for the first time that intensive blood glucose control in type 2 diabetes reduces myocardial infarction risk by 16%, and that intensively metformin-treated overweight patients had a 35-40% reduced mortality risk compared with patients treated only if marked hyperglycemia was present. NEJM Volume 353:2643-2653