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Improved Meal-Related ß-Cell Function and Insulin Sensitivity by the Dipeptidyl Peptidase-IV Inhibitor Vildagliptin in Metformin-Treated Patients With Type 2 Diabetes Over 1Year

¹ Department of Medicine, Lund University, Lund, Sweden
² Metabolic Unit, Institute of Biomedical Engineering, Italian National Research Council, Padua, Italy
³ Novartis Pharmaceuticals, East Hanover, New Jersey
⁴ Novartis Pharma, Basel, Switzerland

Address correspondence and reprint requests to Dr. Bo Ahrén, Department of Medicine, Lund University, B11 BMC, SE-221 84 Lund, Sweden. E-mail: bo.ahren{at}med.lu.se

OBJECTIVE—To examine the effects of dipeptidyl peptidase-IV (DPP-4) inhibition on meal-related ß-cell function and insulin sensitivity over 52 weeks in type 2 diabetes.

RESEARCH DESIGN AND METHODS—In a 12-week core study, placebo (n = 51) or vildagliptin (n = 56; 50 mg OD) was added to metformin treatment (1.5–3.0 mg/day). A 40-week extension followed in 71 patients. Meal tests were performed at 0, 12, 24, and 52 weeks; glucose, insulin, and C-peptide were evaluated.

RESULTS—In subjects completing 52 weeks with participation in all meal tests (n = 57), HbA_1c (A1C) decreased in the vildagliptin/metformin group (VM group, n = 31) but increased in the placebo/metformin group (PM group, n = 26; between-group difference –1.0 ± 0.2%; P < 0.001; baseline of all subjects combined 7.7 ± 0.1%). Also, fasting glucose decreased in the VM group but increased in the PM group (difference –0.9 ± 0.3 mmol/l, P = 0.016; baseline 9.8 ± 0.3 mmol/l). Insulin secretion (postmeal suprabasal area under the 0- to 30-min C-peptide curve divided by the 30-min increase in glucose) was increased in the VM group but was reduced in the PM group (difference +0.011 ± 0.03 pmol/l 30 min/mmol/l, P = 0.018; baseline 0.036 ± 0.02). Insulin sensitivity during meal ingestion (oral glucose insulin sensitivity) increased in the VM group but was not altered in the PM group (difference +27 ± 4 ml · min^–1 · m^–2, P = 0.036; baseline 246 ± 6). Insulin secretion related to insulin sensitivity (adaptation index) increased in the VM group but decreased in the PM group (difference +3.2 ± 1.0, P = 0.040; baseline 9.1 ± 0.5). The change in adaptation index correlated to the change in A1C (r = –0.39, P = 0.004).

CONCLUSIONS—This study presents evidence that DPP-4 inhibition by vildagliptin when added to metformin in type 2 diabetes over 52 weeks improves ß-cell function along with improved postmeal insulin sensitivity.

Abbreviations: AUC, area under the curve • DPP-4, dipeptidyl peptidase-IV • GLP-1, glucagon-like peptide-1 • HOMA-IR, homeostasis model assessment of insulin resistance • OGIS, oral glucose insulin sensitivity • PM, placebo/metformin • VM, vildagliptin/metformin

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