Twelve-week Monotherapy with the DPP-4 Inhibitor Vildagliptin Improves Glycemic Control in Subjects with Type 2 Diabetes

R. E. Pratley; S. Jauffret-Kamel; E. Galbreath; D. Holmes

doi:10.1055/s-2006-944546

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2006; 38(6): 423-428
DOI: 10.1055/s-2006-944546

Original Clinical

Twelve-week Monotherapy with the DPP-4 Inhibitor Vildagliptin Improves Glycemic Control in Subjects with Type 2 Diabetes

R. E. Pratley¹ , S. Jauffret-Kamel² , E. Galbreath³ , D. Holmes²

¹University of Vermont College of Medicine, Burlington, VT, USA
²Novartis Pharma AG, Basel, Switzerland
³Novartis Pharmaceuticals, East Hanover, NJ, USA

Abstract

Inhibition of dipeptidyl peptidase-4 enhances the activity of incretin hormones, improving glycemic control in subjects with type 2 diabetes. This twelve-week randomized, double-masked, placebo-controlled study assessed the efficacy and tolerability of the specific and potent oral dipeptidyl peptidase-4 inhibitor, vildagliptin (25 mg, bid, n = 70) vs. placebo (bid, n = 28) in previously diet-treated subjects with type 2 diabetes. Standardized meal tests were performed at baseline and endpoint. The between-group difference in adjusted mean change in HbA_1c from baseline to endpoint was - 0.6 ± 0.2 % (p = 0.0012) for the whole cohort (baseline 8.0 %) and - 1.2 % for subjects with baseline HbA_1c 8.0 - 9.5 %. Fasting glucose and mean prandial glucose were reduced by 1.1 ± 0.4 (p = 0.0043) and 1.9 ± 0.5 mmol/l (p < 0.0001), respectively. The between-group differences in corrected insulin response at peak glucose and mean prandial C-peptide were + 0.06 ± 0.02 (p = 0.0258) and + 0.10 ± 0.03 nmol/l (p = 0.0031), respectively. Vildagliptin had no effect on fasting lipid levels or body weight. The incidence of adverse events was similar in subjects receiving placebo (71.4 %) and vildagliptin (55.7 %). Conclusion: monotherapy with vildagliptin is well tolerated and improves glycemic control in diet-treated subjects with type 2 diabetes. Concomitant improvements in β-cell function were also observed. Subjects with higher baseline HbA_1c levels showed greater response.

Key words

Dipeptidyl peptidase IV - efficacy - glycemic control - incretin

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Referenzen

References

1 Ahren B, Larsson H, Holst J J. Effects of glucagon-like peptide-1 on islet function and insulin sensitivity in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1997; 82 473-478
2 Vella A, Rizza R A. Extrapancreatic effects of GIP and GLP-1. Horm Metab Res. 2004; 36 830-836
3 Zander M, Madsbad S, Madsen J L, Holst J J. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and b-cell function in type 2 diabetes: a parallel-group study. Lancet. 2002; 359 824-830
4 Holst J J, Orskov C. The incretin approach for diabetes treatment: modulation of islet hormone release by GLP-1 agonism. Diabetes. 2004; 53 (suppl 3) S197-S204
5 Ahren B, Schmitz O. GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. Horm Metab Res. 2004; 36 867-876
6 Mentlein R, Gallwitz B, Schmidt W E. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7 - 36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem. 1993; 214 829-835
7 Nauck M A. Glucagon-like Peptide 1 (GLP-1) in the treatment of diabetes. Horm Metab Res. 2004; 36 852-858
8 Amylin Pharmaceuticals, Inc .Byetta™ (exenatide injection) [Prescribing Information]. San Diego; Amylin Pharmaceuticals, Inc. 2005
9 Villhauer E B, Brinkman J A, Naderi G B. et al . 1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem. 2003; 46 2774-2789
10 Mari A, Sallas W M, He Y L. et al . The dipeptidyl peptidase-IV inhibitor, vildagliptin, improves model-assessed b-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab. 2005; 90 4888-4894
11 Ahren B, Pacini G, Foley J E, Schweizer A. Improved meal-related b-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
12 Ahren B, Landin-Olsson M, Jansson P-A. et al . Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab. 2004; 89 2078-2084
13 Ahren B, Gomis R, Standl E, Mills D, Schweizer A. 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
14 Matthews D R, Hosker J P, Rudenski A S. et al . Homeostasis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28 412-419
15 Sluiter W J, Erkelens D W, Reitsma W D, Doorenbos H. Glucose tolerance and insulin release, a mathematical approach I. Assay of the beta-cell response after oral glucose loading. Diabetes. 1976; 25 241-244
16 Matsuda M, DeFronzo R A. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999; 22 1462-1470
17 Ahren B, Simonsson E, Larsson H. et al . Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes. Diabetes Care. 2002; 25 869-875

Richard E. Pratley, M. D.

Diabetes and Metabolism Translational Medicine Unit

University of Vermont College of Medicine · FAHC/Arnold 3412 · One South Prospect Street · Burlington · VT 05401 · USA ·

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eMail: richard.pratley@uvm.edu