Pioglitazone plus metformin therapy best for improving insulin resistance
MedWire News: A comparison of the long-term effect of four oral antidiabetes treatment regimens shows that therapy based on the combination of pioglitazone and metformin is associated with the greatest improvement in insulin resistance parameters.
Insulin resistance, together with beta-cell dysfunction, leads to the appearance and gradual progression of Type 2 diabetes, and is an independent predictor for cardiovascular disease in these patients.
In the first clinical trial directly comparing the insulin-sensitizing effects of different oral antidiabetes drug regimens, Giuseppe Derosa (University of Pavia, Italy) and co-workers randomly assigned 272 overweight, treatment-naïve patients with Type 2 diabetes and poor glycemic control to receive one of four treatment regimens for 15 months.
The compared treatments were metformin 1000 mg/day alone, pioglitazone 15 mg/day alone, pioglitazone/metformin 15 mg/850 mg/day, and glimepiride/metformin 2 mg/850 mg/day.
Patients received instruction on dietary intake and were encouraged to increase physical activity.
Insulin resistance was determined at baseline, and after 3 and 15 months by euglycemic hyperinsulinemic clamp, which measures the amount of glucose necessary to compensate for an increased insulin level without causing hypoglycemia. Parameters studied included fasting plasma insulin (FPI), postprandial plasma insulin (PPI), glucose infusion rate (GIR), and total glucose requirement (TGR).
Presenting the results in the journal Metabolism Clinical and Experimental, the authors report that, with the exception of PPI, insulin resistance-related parameters significantly improved in all the groups compared with baseline, but more so with pioglitazone/metformin. Mean improvements in this group were -30% for FPI, 52.6% for GIR, and 29% for TGR, compared with a mean improvement in the other groups of -10%, 23%, and 12%, respectively.
All treatments except the glimepiride-based regimen also achieved a significant reduction in PPI. In the pioglitazone/metformin-treated group, PPI decreased by 33% versus baseline, whereas it increased by 9.6% in the glimepiride/metformin group.
Glycated hemoglobin (HbA1c) decreased in all groups, but the greatest reduction was observed in the pioglitazone/metformin group. Decreases in fasting plasma glucose and postprandial plasma glucose were also greatest with this regimen.
An increase in body mass index (BMI) was observed in the groups treated with pioglitazone alone and with glimepiride/metformin at 15 months, whereas no BMI changes were observed in the other two groups compared with the baseline.
“Pioglitazone/metformin-based therapeutic control is associated with the most quantitatively relevant improvement in insulin resistance-related parameters, whereas the sulfonylurea-metformin-including protocol has less relevant effects,” conclude the authors.
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By Jenny Grice