Thiazolidinedione lowers blood pressure, improves lipids in type 2 diabetes

Cardiology Review® Online, July 2004, Volume 21, Issue 7

ORLANDO—The insulin sensitizer pioglitazone reduces blood pressure in patients with type 2 diabetes. Pioglitazone also has beneficial effects on lipid abnormalities that occur in patients with diabetes, metabolic syndrome, or both. These findings were released at the 64th Annual Scientific Sessions of the American Diabetes Association.

In a study of 3,140 patients with type 2 diabetes and hypertension, all patients received open-label pioglitazone, 30 mg daily, for 2 weeks. Hypertension was classified as Stage I or Stage II according to current National Institutes of Health criteria (JNC 7), under which Stage I is defined as 140 to 159/90 to 99 mm Hg and Stage II is defined as ≥ 160/≥ 100 mm Hg. Pioglitazone lowered blood pressure by a mean of 6.9/3.1 mm Hg from baseline in patients with Stage I hypertension, and by 18.7/8.3 mm Hg in patients with Stage II hypertension. “Hypertension is frequently diagnosed in patients with type 2 diabetes and is often present years before disease onset,” said lead investigator Thomas Konrad, MD, assistant professor of medicine, Institute for Metabolic Research, Frankfurt, Germany. “In these patients, controlling hypertension is as important as controlling the glycemic level. These blood pressure lowering findings are remarkable because they suggest that pioglitazone may be able to impact certain cardiovascular disease risk factors in patients with type 2 diabetes.” Pioglitazone is thought to decrease blood pressure by reducing vascular resistance by improving endothelial function, he added.

Other clinical studies presented at the meeting showed that pioglitazone has favorable effects on the dyslipidemia that occurs commonly with diabetes or metabolic syndrome. Investigators assessed 2,444 patients with type 2 diabetes who were enrolled in one of two prospective, randomized, double-blind, multicenter, multinational trials in which the patients were randomly assigned to receive pioglitazone, a sulfonylurea, or metformin for as long as 52 weeks. The effects of the three treatments on components of diabetic dyslipidemia were studied.

High-density lipoprotein (HDL) cholesterol increased by 19.7% in patients assigned to pioglitazone, compared with a 10.5% increase among those assigned to metformin and 7.4% among those assigned to a sulfonylurea. The difference in HDL cholesterol change from baseline was significantly superior in the pioglitazone-treated patients versus the other two groups (P < .0001). Pioglitazone was also significantly superior to the other two treatment groups in decreasing triglycerides (—10.4%, –0.6%, and –4.0% with pioglitazone, metformin, and sulfo-nylurea, respectively) and the ratio of total to HDL cholesterol (–9.8%, –7.7%, and –9.0%, respectively).

In another study of 1,269 patients with type 2 diabetes, pioglitazone and metformin were evaluated when added to existing sulfonylurea ther-apy; pioglitazone and sulfonylurea were also evaluated when added to existing metformin therapy. The investigators found that pioglitazone added to the sulfonylurea resulted in a 17% decrease in triglycerides compared with a 9% decrease when metformin was added to the sulfo-nylurea (P = .001). Pioglitazone added to metformin was associated with a 23% decrease in triglycerides compared with a 7% increase when sulfonylurea was added to metformin

(P = .001). Pioglitazone added to the sulfonylurea also improved HDL cholesterol by 21%, whereas the metformin addition was associated with a 15% increase (P = .001). When pioglitazone was added to metformin, HDL cholesterol improved by 22%; sulfonylurea added to metformin increased HDL cholesterol only an additional 7% (P = .001).