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  • Title: Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes.
    Author: Lindsay JR, Duffy NA, McKillop AM, Ardill J, O'Harte FP, Flatt PR, Bell PM.
    Journal: Diabet Med; 2005 May; 22(5):654-7. PubMed ID: 15842525.
    Abstract:
    AIMS: Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important insulinotropic hormones that enhance the insulin secretory response to feeding. Their potential for treating Type 2 diabetes is limited by short biological half-life owing to degradation by dipeptidyl peptidase IV (DPP IV). We investigated the acute effects of metformin on DPP IV activity in Type 2 diabetes to elucidate inhibition of DPP IV as a possible mechanism of action. METHODS: Eight fasting subjects with Type 2 diabetes (5M/3F, age 53.1+/-4.2 years, BMI 36.8+/-1.8 kg/m2, glucose 8.9+/-1.2 mmol/l, HbA1c 7.8+/-0.6%) received placebo or metformin 1 g orally 1 week apart in a random, crossover design. RESULTS: Following metformin, DPP IV activity was suppressed compared with placebo (AUC0-6 h 3230+/-373 vs. 5764+/-504 nmol ml/l, respectively, P=0.001). Circulating glucose, insulin and total GLP-1 were unchanged. Metformin also concentration-dependently inhibited endogenous DPP IV activity in vitro in plasma from Type 2 diabetic subjects. CONCLUSION: Oral metformin effectively inhibits DPP IV activity in Type 2 diabetic patients, suggesting that the drug may have potential for future combination therapy with incretin hormones.
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