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

M. A. Nauck, G. Meininger, D. Sheng, L. Terranella, Peter P. Stein, P. Tesone, T. Davis, S. Colagiuri, R. Prager, G. Schernthaner, H. Toplak, T. Wascher, F. Coucke, M. De Meulemeester, J. Ducobu, J. Gross, M. T. Zanella, G. Godoy, E. Hernandez, V. ProfozicM. Kvapil, B. Tomas, P. Umlauf, J. Zemanova, K. Egstrup, A. Hansen, K. Hermansen, J. Eriksson, J. Lahtela, L. Niskanen, P. Salmela, B. Bauduceau, J. Bringer, G. Charpentier, M. Krempf, M. Marre, G. Weryha, J. Adler, H. Bouzo, K. M. Derwahl, M. Hanefeld, H. G. Kirchberg, G. Klausmann, C. Klein, R. Lehmann, M. Nauck, E. Oerter, E. D. Schulze, A. Weisbrod, K. Weyland, T. Zoller, K. Lam, J. Vadasz, G. Vandorfi, G. Baule, G. DeMattia, S. Gambardella, G. Ghirlanda, R. Lauro, S. Squatrito, L. Zabuliene, S. Chan, M. Mohamed, L. Sauque, W. A. de Backer, E. H.R. Wins, J. Benatar, R. Scott, J. Cooper, K. Furuseth, B. Kulseng, G. Molina, A. Rodriguez, E. Pacheco, K. Markiewicz, G. Pinis, J. Raposo, G. Teles, P. Eng, L. Burgess, R. Moore, J. Wing, A. Calle-Pascual, S. D. Garcia, F. V. Roca, J. L. Pino, J. M. Puig, E. Eizyk, A. Frid, P. A. Lagerback, U. Smith, M. Eddé, H. Saner, C. J. Chang, C. M. Hwu, S. T. Tu, R. Demirtunc, I. Satman, D. Haworth, P. Kopelman, R. Pieters, B. Silvert, R. Watt, Andrew Ahmann, S. Andrews, L. Barai, E. Barranco, R. Bettis, R. Blank, R. Brazg, S. Brazinsky, T. Bruya, F. Burch, E. Busick, R. Butcher, A. Caos, M. Chen, J. Clower, K. Cohen, G. Collins, J. Cook, M. Davidson, P. Denker, W. Drummond, J. Earl, A. Eisenberg, A. Forker, R. Garcia, H. Geisberg, J. Gilbert, R. Gilman, D. Gleason, R. Goldberg, F. Goldstein, S. Greco, P. Hollander, M. Jacobs, A. Jain, R. Kaplan, M. Kashyap, A. F. Kawley, H. Kerstein, Y. Khronusova, C. Laffer, A. Lewin, D. Linden, R. Lipetz, T. Littlejohn, J. Lochner, S. Mather, J. McGettigan, R. McNeill, N. Mezitis, J. Mitchell, L. Morales, A. Odugbesan, L. Padget, N. Patel, R. Pratley, J. Reusch, J. Robinson, J. Ruckle, M. Sandberg, M. J. Schear, D. Schumacher, R. Severance, J. Shapiro, M. Shomali, D. Silkiner, H. Simon, P. Smith, J. Stevens, G. Umpierrez, R. Wade, M. Weerasinghe, M. Weinberg, B. Wittmer, S. Yale

Research output: Contribution to journalArticle

568 Scopus citations

Abstract

Aim: To compare the efficacy and safety of sitagliptin vs. glipizide in patients with type 2 diabetes and inadequate glycaemic control [haemoglobin A1c (HbA1c) ≥ 6.5 and ≤10%] on metformin monotherapy. Methods: After a metformin dose titration/stabilization period (≥1500 mg/day), 1172 patients were randomized to the addition of sitagliptin 100 mg q.d. (N = 588) or glipizide 5 mg/day (uptitrated to a potential maximum 20 mg/day) (N = 584) for 52 weeks. The primary analysis assessed whether sitagliptin was non-inferior to glipizide regarding HbA1c changes from baseline at Week 52 using a per-protocol approach. Results: From a mean baseline of 7.5%, HbA1c changes from baseline were -0.67% at Week 52 in both groups, confirming non-inferiority. The proportions achieving an HbA1c < 7% were 63% (sitagliptin) and 59% (glipizide). Fasting plasma glucose changes from baseline were -0.56 mmol/l (-10.0 mg/dl) and -0.42 mmol/l (-7.5 mg/dl) for sitagliptin and glipizide, respectively. The proportion of patients experiencing hypoglycaemia episodes was significantly (p < 0.001) higher with glipizide (32%) than with sitagliptin (5%), with 657 events in glipizide-treated patients compared with 50 events in sitagliptin-treated patients. Sitagliptin led to weight loss (change from baseline = -1.5 kg) compared with weight gain (+1.1 kg) with glipizide [between-treatment difference (95% confidence interval) = -2.5 kg (-3.1, -2.0); p < 0.001]. Conclusions: In this study, the addition of sitagliptin compared with glipizide provided similar HbA1c-lowering efficacy over 52 weeks in patients on ongoing metformin therapy. Sitagliptin was generally well tolerated, with a lower risk of hypoglycaemia relative to glipizide and with weight loss compared with weight gain with glipizide.

Original languageEnglish (US)
Pages (from-to)194-205
Number of pages12
JournalDiabetes, Obesity and Metabolism
Volume9
Issue number2
DOIs
StatePublished - Mar 2007
Externally publishedYes

Keywords

  • DPP-IV
  • Dipeptidyl peptidase-IV
  • Incretins
  • MK-0431
  • Sulfonylureas

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Nauck, M. A., Meininger, G., Sheng, D., Terranella, L., Stein, P. P., Tesone, P., Davis, T., Colagiuri, S., Prager, R., Schernthaner, G., Toplak, H., Wascher, T., Coucke, F., De Meulemeester, M., Ducobu, J., Gross, J., Zanella, M. T., Godoy, G., Hernandez, E., ... Yale, S. (2007). 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, Obesity and Metabolism, 9(2), 194-205. https://doi.org/10.1111/j.1463-1326.2006.00704.x