Horm Metab Res 2009; 41(12): 905-909
DOI: 10.1055/s-0029-1234042
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Efficacy and Safety Comparison Between the DPP-4 Inhibitor Vildagliptin and the Sulfonylurea Gliclazide After Two Years of Monotherapy in Drug-naïve Patients with Type 2 Diabetes

J. E. Foley1 , S. Sreenan2
  • 1Clinical Research & Development, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
  • 2Department of Endocrinology, Royal College of Surgeons in Ireland, Connolly Hospital, Dublin, Ireland
Further Information

Publication History

received 06.05.2009

accepted 30.06.2009

Publication Date:
24 August 2009 (online)

Abstract

This report is part of the overall evaluation of using vildagliptin in the treatment of type 2 diabetes. Here the results of a multi-center, double-blind, randomized, active-controlled study designed to compare the efficacy and safety of two years of monotherapy with vildagliptin 50 mg bid and gliclazide up to 320 mg/day in drug-naïve patients with type 2 diabetes are reported. A total of 546 patients were randomized and ∼74% of patients completed the study in each group. HbA1c values were slightly higher in the gliclazide group (HbA1c of 8.7±0.1% vs. 8.5±0.1% in the vildagliptin group). The mean reduction in HbA1c from baseline to Week 104 was −0.5% in the vildagliptin group and −0.6% in the gliclazide group. The associated 95% confidence interval (CI) for the between-group difference (0.13%) in mean change was (−0.06%, 0.33%). Thus, noninferiority based on an upper limit of the CI of 0.3% was not met. In the vildagliptin group, weight increased by 0.8±0.2 kg compared to 1.6±0.2 kg in the gliclazide group (p<0.01). Mild hypoglycemia was recorded in 0.7% of patients in the vildagliptin group and in 1.7% in the gliclazide group. Both drugs were well tolerated. In summary, vildagliptin monotherapy resulted in improved glycemic control in drug-naïve patients with type 2 diabetes. Although the hypothesis of noninferiority to gliclazide was not borne out statistically, the reductions in HbA1c were similar over a two year period and vildagliptin had significant benefits in terms of less weight gain and less hypoglycemia.

References

  • 1 UK Prospective Diabetes Study (UKPDS) Group. . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).  Lancet. 1998;  352 837-853
  • 2 Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: Scientific review.  JAMA. 2002;  287 360-372
  • 3 Hermansen K, Mortensen LS. Bodyweight changes associated with antihyperglycaemic agents in type 2 diabetes mellitus.  Drug Saf. 2007;  30 1127-1142
  • 4 Ahrén B, Foley JE. The islet enhancer vildagliptin: mechanisms of improved glucose metabolism.  Int J Pract. 2008;  62 8-14
  • 5 Dejager S, Baron MA, Schweizer A. DPP-4 inhibitors: review of vildagliptin phase 3 data.  Rev Endocrinol. 2007;  1 47-51
  • 6 Dejager S, Razac S, Foley JE, Schweizer A. Vildagliptin in drug-naïve patients with type 2 diabetes: a 24-week, double-blind, randomized, placebo-controlled, multiple-dose study.  Horm Metab Res. 2007;  39 218-223
  • 7 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
  • 8 Schweizer A, Couturier A, Foley JE, Dejager S. Comparison between vildagliptin and metformin to sustain reductions in HbA1c over one year in drug-naïve patients with type 2 diabetes.  Diabetic Med. 2007;  24 955-961
  • 9 Scherbaum WA, Schweizer A, Mari A, Nilsson PM, Lalanne G, Jauffret S, Foley JE. Efficacy and tolerability of vildagliptin in drug-naïve patients with type 2 diabetes and mild hyperglycemia.  Diabetes Obes Metab. 2008;  10 675-682
  • 10 Garber AJ, Foley JE, Banerji MA, Ebeling P, Gudbjörnsdottir S, Camisasca RP, Couturier A, Baron MA. Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulfonylurea.  Diabetes Obes Metab. 2008;  10 1047-1056
  • 11 Fonseca V, Schweizer A, Albrecht D, Baron MA, Chang I, Dejager S. Addition of vildagliptin to insulin improves glycaemic control in type 2 diabetes.  Diabetologia. 2007;  50 1148-1155
  • 12 Rosenstock J, Baron MA, Dejager S. et al . Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes: a 24-week, double-blind, randomized trial.  Diabetes Care. 2007;  30 217-223
  • 13 Barnett A. Potential role of oral DPP-4 inhibitors in the ADA/EASD consensus statement algorithm for achieving and maintaining tight glycaemic control in type 2 diabetes: recommendations for oral antidiabetic agents.  Int J Clin Pract. 2007;  61 12-18
  • 14 De Heer J, Holst JJ. Sulfonylurea compounds uncouple the glucose dependence of the insulinotropic effect of glucagon-like peptide 1.  Diabetes. 2007;  56 438-443
  • 15 Ferrannini E, Fonseca V, Zinman B, Matthews D, Ahrén B, Byiers S, Shao Q, Dejager S. Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy.  Diabetes Obes Metab. 2009;  11 157-166
  • 16 Bunck MC, Diamant M, Cornér A, Eliasson B, Malloy JL, Shaginian RM, Deng W, Kendall DM, Taskinen MR, Smith U, Yki-Järvinen H, Heine RJ. One-year treatment with exenatide improves β-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial.  Diabetes Care. 2009;  32 762-768
  • 17 Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O’Neill MC, Zinman B, Viberti G. ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy.  N Engl J Med. 2006;  355 2427-2443

1 * This trial (NCT00102388) is registered with ClinicalTrials. gov.

Correspondence

J. E. Foley

Clinical Research & Development

One Health Plaza

Novartis Pharmaceuticals

East Hanover

NJ

USA

Phone: +1/862/778 32 58

Fax: +1/973/781 84 96

Email: james.foley@novartis.com

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