Efficacy and Tolerability of Vildagliptin in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy

Abstract

The aim of the study was to evaluate the efficacy and safety of vildagliptin added to metformin in patients with type 2 diabetes mellitus. A multicentre, double-blind, randomized, placebo-controlled, 24-week study in patients inadequately controlled with metformin (HbA_1c 7.5–11%) was designed. Patients were randomized to vildagliptin (Galvus^®) 100 mg given in the morning (AM), vildagliptin 100 mg given in the evening (PM), or placebo. The primary objective was to demonstrate that HbA_1c reduction with once-daily vildagliptin 100 mg AM dosing is superior to placebo. Change from baseline to study endpoint in adjusted mean (SE) HbA_1c improved significantly with vildagliptin AM dosing (−0.66 [0.11] versus 0.17% [0.11] with placebo; p <0.001). Subgroup analyses revealed that HbA_1c reduction from baseline was greatest in those patients who had the highest baseline HbA_1c levels. According to a predefined set of response criteria, the percentage of responder patients was significantly greater in the vildagliptin AM dosing group than in the placebo group for all responder definitions. Further analysis also revealed comparable efficacy between AM and PM dosing. Body weight remained generally stable in the combined vildagliptin group (+0.06 kg) and decreased with placebo (–0.69 kg); the incidence of adverse events was similar with vildagliptin AM dosing and placebo (30.4 and 34.4%, respectively). Vildagliptin 100 mg given as a morning dose is an effective and well-tolerated treatment option in patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy, and is equally efficacious when given as either a morning or evening dose.

Key words

Galvus^® - add-on therapy - DPP-4 inhibitor

References

• 1 Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial.  Diabetes Obes Metab. 2007;  9 194-205
• 2 Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, Zinman B. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes.  Diabetes Care. 2006;  29 1963-1972
• 3 Saydah S, Cowie C, Eberhardt MS, Rekeneire N De, Narayan KM. Race and ethnic differences in glycemic control among adults with diagnosed diabetes in the United States.  Ethn Dis. 2007;  17 529-535
• 4 Bosi E, Camisasca RP, Collober C, Rochotte E, Garber AJ. Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin.  Diabetes Care. 2007;  30 890-895
• 5 Bolli G, Dotta F, Rochotte E, Cohen SE. Efficacy and tolerability of vildagliptin vs. pioglitazone when added to metformin: a 24-week, randomized, double-blind study.  Diabetes Obes Metab. 2008;  10 82-90
• 6 Ahrén B, Mills D, Gomis R, Schweizer A, Mills D. Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes.  Diabetes Care. 2004;  27 2874-2880
• 7 Ahrén B, Pacini G, Foley JE, Schweizer A. Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year.  Diabetes Care. 2005;  28 1936-1940
• 8 Utzschneider KM, Tong J, Montgomery B, Udayasankar J, Gerchman F, Marcovina SM, Watson CE, Ligueros-Saylan MA, Foley JE, Holst JJ, Deacon CF, Kahn SE. The dipeptidyl peptidase-4 inhibitor vildagliptin improves beta-cell function and insulin sensitivity in subjects with impaired fasting glucose.  Diabetes Care. 2008;  31 108-113
• 9 Pratley RE, Schweizer A, Rosenstock J, Foley JE, Banerji MA, Pi-Sunyer FX, Mills D, Dejager S. Robust improvements in fasting and prandial measures of beta-cell function with vildagliptin in drug-naïve patients: analysis of pooled vildagliptin monotherapy database.  Diabetes Obes Metab. 2007;  10 931-938
• 10 Ahrén B, Pacini G, Tura A, Foley JE. Improved meal-related insulin processing contributes to the enhancement of β-cell function by the DPP-4 inhibitor vildagliptin in patients with type 2 diabetes.  Horm Metab Res. 2007;  39 826-829
• 11 Pi-Sunyer FX, Schweizer A, Mills D, Dejager S. Efficacy and tolerability of monotherapy in drug-naïve patients with type 2 diabetes.  Diabetes Res Clin Pract. 2007;  76 132-138

Correspondence