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| |  EASD: Repaglinide Plus Metformin Increases Insulin Secretion And Sensitivity In Type 2 Diabetics By David Jack Special to DG News
GLASGOW, SCOTLAND -- September 13, 2001 -- A recent study has shown that acute treatment with repaglinide increases insulin release and secretion, reducing postprandial hyperglycemia in a dose-dependent manner. Repaglinide is a relatively new, rapid-acting, oral, antidiabetic agent. This study was headed by Dr. Natalia Roudovitch, Benjamin Franklin Clinic, Free University of Berlin, Germany, to investigate the hypoglycemic effect of repaglinide under hyper- and euglycemic clamp conditions. The researchers also aimed to identify the effect of the combination of repaglinide with metformin on insulin sensitivity. The study had a randomized, fixed-dose, placebo-controlled design. It lasted a total of three weeks. Week 1 was a run-in period during which baseline evaluations, physical examinations, laboratory testing and recording detailed medical histories were carried out. Week 2 involved treatment with placebo (1 mg x 3/day) plus metformin (850 mg x 3/day) and week 3 involved repaglinide (1 mg x 3/d) plus metformin (850 mg x 3/day). A total of 11 patients with type 2 diabetes were recruited with a mean age of 58 (range of 41-66) years, a mean body mass index of 32.2 (range 23 - 45) kg/m², and a mean duration of diabetes of 8.2 years (range 0.2 - 15). Patients were treated by diet and/or oral antidiabetic drugs. The acute insulin response to glucose and the second phase of insulin secretion under hyperglycemic conditions were both significantly increased in hyperglycemic clamps with repaglinide (acute insulin response to insulin [AIRglu] 1.23±0.4 versus 0.73±0.4 h.µU/L, p<0.01 and area under the curve [AUC] (25-180 min) 95.8±25.7 versus 52±16.5 h.µU/L, p<0.01). The insulin sensitivity index increased after one week of combination repaglinide plus metformin therapy compared with that after one week of placebo plus metformin (6.67±1.8 versus 4.96±1.3 mg/kg.min/mU, p<0.05). These results suggest that repaglinide acts on a number of key steps involved in the metabolism of carbohydrates in type 2 diabetics, Dr. Roudovitch said. The significant enhancement of the insulin sensitivity index seen with repaglinide plus metformin suggests that the two agents have a synergistic effect on insulin sensitivity in such patients, he concluded.
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