Diabetes Care, Vol 20, Issue 4 597-606, Copyright © 1997 by American Diabetes Association

ARTICLES

Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM. Results of two multicenter, randomized, placebo-controlled clinical trials. The Glipizide Gastrointestinal Therapeutic System Study Group

DC Simonson, IA Kourides, M Feinglos, H Shamoon and CT Fischette
Department of Medicine, Joslin Diabetes Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

OBJECTIVE: To investigate the efficacy, safety, and dose-response characteristics of an extended-release preparation of glipizide using the gastrointestinal therapeutic system (GITS) on plasma glucose, glycosylated hemoglobin (HbA1c), and insulin secretion to a liquid-mixed meal in NIDDM patients. RESEARCH DESIGN AND METHODS: Two prospective, randomized, double-blind, placebo-controlled, multicenter clinical trials were performed in 22 sites and 347 patients with NIDDM (aged 59 +/- 0.6 years; BMI, 29 +/- 0.3 kg/m2; known diabetes duration, 8 +/- 0.4 years) were studied. Each clinical trial had a duration of 16 weeks with a 1-week washout, 3-week single-blind placebo phase, 4-week titration to a fixed dose, and 8-week maintenance phase at the assigned dose. In the first trial, once-daily doses of 5, 20, 40, or 60 mg glipizide GITS were compared with placebo in 143 patients. In the second trial, doses of 5, 10, 15, or 20 mg of glipizide GITS were compared with placebo in 204 patients. HbA1c, fasting plasma glucose (FPG), insulin, C-peptide, and glipizide levels were determined at regular intervals throughout the study. Postprandial plasma glucose (PPG), insulin, and C-peptide also were determined at 1 and 2 h after a mixed meal (Sustacal). RESULTS: All doses of glipizide GITS in both trials produced significant reductions from placebo in FPG (range -57 to -74 mg/dl) and HbA1c (range -1.50 to -1.82%). Pharmacodynamic analysis indicated a significant relationship between plasma glipizide concentration and reduction in FPG and HbA1c over a dose range of 5-60 mg, with maximal efficacy achieved at a dose of 20 mg for FPG and at 5 mg for HbA1c. PPG levels were significantly lower, and both postprandial insulin and C-peptide levels significantly higher in patients treated with glipizide GITS compared with placebo. The percent reduction in FPG was comparable across patients with diverse demographic and clinical characteristics, including those with entry FPG > or = 250 mg/dl, resulting in greater absolute decreases in FPG and HbA1c in patients with the most severe hyperglycemia. Despite the forced titration to a randomly assigned dose, only 11 patients in both studies discontinued therapy because of hypoglycemia. Glipizide GITS did not alter lipids levels or produce weight gain. CONCLUSIONS: The once-daily glipizide GITS 1) lowered HbA1c, FPG, and PPG over a dose range of 5-60 mg, 2) was maximally effective at 5 mg (using HbA1c) or 20 mg (using FPG) based on pharmacokinetic and pharmacodynamic relationships, 3) maintained its effectiveness in poorly controlled patients (those with entry FPG > or = 250 mg/dl), 4) was safe and well tolerated in a wide variety of patients with NIDDM, and 5) did not produce weight gain or adversely affect lipids.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Selvin, S. Bolen, H.-C. Yeh, C. Wiley, L. M. Wilson, S. S. Marinopoulos, L. Feldman, J. Vassy, R. Wilson, E. B. Bass, et al. Cardiovascular Outcomes in Trials of Oral Diabetes Medications: A Systematic Review Arch Intern Med, October 27, 2008; 168(19): 2070 - 2080. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden Approaches to Treatment of Type 2 Diabetes Diabetes Care, August 1, 2008; 31(8): 1697 - 1703. [Full Text] [PDF]

				D. F. Kruger Exploring the Pharmacotherapeutic Options for Treating Type 2 Diabetes The Diabetes Educator, May 1, 2008; 34(Supplement_3): 60S - 65S. [Abstract] [Full Text] [PDF]

				W.S. Leslie, C.R. Hankey, and M.E.J. Lean Weight gain as an adverse effect of some commonly prescribed drugs: a systematic review QJM, July 1, 2007; 100(7): 395 - 404. [Abstract] [Full Text] [PDF]

				C. Triplitt, L. Glass, Y. Miyazaki, E. Wajcberg, A. Gastaldelli, E. De Filippis, E. Cersosimo, and R. A. DeFronzo Comparison of glargine insulin versus rosiglitazone addition in poorly controlled type 2 diabetic patients on metformin plus sulfonylurea. Diabetes Care, November 1, 2006; 29(11): 2371 - 2377. [Abstract] [Full Text] [PDF]

				C. D. Miller, D. C. Ziemer, P. Kolm, I. M. El-Kebbi, C. B. Cook, D. L. Gallina, J. P. Doyle, C. S. Barnes, and L. S. Phillips Use of a Glucose Algorithm to Direct Diabetes Therapy Improves A1C Outcomes and Defines an Approach to Assess Provider Behavior. The Diabetes Educator, July 1, 2006; 32(4): 533 - 545. [Abstract] [Full Text] [PDF]

				B. Kimmel and S. E. Inzucchi Oral Agents for Type 2 Diabetes: An Update Clin. Diabetes, April 1, 2005; 23(2): 64 - 76. [Abstract] [Full Text] [PDF]

				Y. Miyazaki, E. De Filippis, M. Bajaj, E. Wajcberg, L. Glass, C. Triplitt, E. Cersosimo, L. J Mandarino, and R. A Defronzo Predictors of improved glycaemic control with rosiglitazone therapy in type 2 diabetic patients: a practical approach for the primary care physician The British Journal of Diabetes & Vascular Disease, January 1, 2005; 5(1): 28 - 35. [Abstract] [PDF]

				M. F. Carroll, A. Gutierrez, M. Castro, D. Tsewang, and D. S. Schade Targeting Postprandial Hyperglycemia: A Comparative Study of Insulinotropic Agents in Type 2 Diabetes J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5248 - 5254. [Abstract] [Full Text] [PDF]

				S. Gahagan, J. Silverstein, Committee on Native American Child Health, and Section on Endocrinology Prevention and Treatment of Type 2 Diabetes Mellitus in Children, With Special Emphasis on American Indian and Alaska Native Children Pediatrics, October 1, 2003; 112(4): e328 - e328. [Abstract] [Full Text] [PDF]

				M. T. Sheehan Current Therapeutic Options in Type 2 Diabetes Mellitus: A Practical Approach Clin. Med. Res., July 1, 2003; 1(3): 189 - 200. [Abstract] [Full Text] [PDF]

				A. D. Morris Addressing Dosing Frequency in Diabetes: A Simple Approach to Improving Adherence to Therapy and Clinical Outcomes The Diabetes Educator, May 1, 2003; 29(3): 440 - 453. [PDF]

				A. Gastaldelli, Y. Miyazaki, M. Pettiti, M. Matsuda, S. Mahankali, E. Santini, R. A. DeFronzo, and E. Ferrannini Metabolic Effects of Visceral Fat Accumulation in Type 2 Diabetes J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5098 - 5103. [Abstract] [Full Text] [PDF]

				Y. Miyazaki, A. Mahankali, M. Matsuda, S. Mahankali, J. Hardies, K. Cusi, L. J. Mandarino, and R. A. DeFronzo Effect of Pioglitazone on Abdominal Fat Distribution and Insulin Sensitivity in Type 2 Diabetic Patients J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2784 - 2791. [Abstract] [Full Text] [PDF]

				Y. Miyazaki, M. Matsuda, and R. A. DeFronzo Dose-Response Effect of Pioglitazone on Insulin Sensitivity and Insulin Secretion in Type 2 Diabetes Diabetes Care, March 1, 2002; 25(3): 517 - 523. [Abstract] [Full Text] [PDF]

				S. E. Inzucchi Oral Antihyperglycemic Therapy for Type 2 Diabetes: Scientific Review JAMA, January 16, 2002; 287(3): 360 - 372. [Abstract] [Full Text] [PDF]

				B. Keidan, J. Hsia, and R. Katz Plasma lipids and antidiabetic agents: a brief overview The British Journal of Diabetes & Vascular Disease, January 1, 2002; 2(1): 40 - 43. [PDF]

				Y. Miyazaki, A. Mahankali, M. Matsuda, L. Glass, S. Mahankali, E. Ferrannini, K. Cusi, L. J. Mandarino, and R. A. DeFronzo Improved Glycemic Control and Enhanced Insulin Sensitivity in Type 2 Diabetic Subjects Treated With Pioglitazone Diabetes Care, April 1, 2001; 24(4): 710 - 719. [Abstract] [Full Text]

				R. A. DeFronzo Pharmacologic Therapy for Type 2 Diabetes Mellitus Ann Intern Med, August 17, 1999; 131(4): 281 - 303. [Abstract] [Full Text] [PDF]