Comparison of conventional and sustained-release formulation of metformin in type 2 diabetics

Vishal V. Ghorpade, Rajesh S. Hiray, Bharti R. Daswani, Balasaheb B. Ghongane


Background: To investigate the effects of metformin sustained-release (MSR) compared with metformin immediate-release (MIR) on glycaemic control, blood pressure, lipid profile and metabolic parameters like weight, waist circumference in type 2 diabetes.

Methods: A prospective, randomized, double blind study was conducted at tertiary healthcare and teaching hospital at Pune, Maharashtra. After obtaining institutional ethical committee approval and written informed consent, 40 newly diagnosed type 2 diabetic patient were randomly assigned to receive metformin immediate release formulation (MIR) 500 mg once 1 week and then twice daily and metformin sustained release formulation (MSR) 500 mg once 1 week and  then 1000mg once daily for 18 weeks. Fasting and post prandial blood glucose level (BGL), HbA1c, blood pressure, lipid profile, weight and waist circumference, were recorded at the start and end of study.

Results: Both MIR and MSR significantly decreased fasting; post prandial BGL and HbA1c at 18 weeks. But no significant difference was seen between two groups. Study did not show any effect on blood pressure and on lipid profile. Both formulations decreased obesity as evident by significant reduction in weight and waist circumference. All patients tolerated both formulations of metformin. Though overall incidences of adverse effects are less with sustained release formulation, difference was not significant between two groups.

Conclusions: To conclude, both metformin immediate release and sustained release formulations achieved comparable glycaemic control and sustained release formulation would be as effective as immediate release formulation with advantage of being reduce daily intake of tablets.


Metformin, Sustained release, Tolerability

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Powers AC. Diabetes mellitus. In D.L. Kasper, E. Braunwald, A.S. Fauci editor. Harrison’s Principal of Internal Medicine. 17th edition. McGraw Hill Publishers; 2009:2152-2179.

Johnson AB, Webster JM, Sum CF, Heseltine L, Argyraki M, Cooper BG et al. The impact of metformin therapy on hepatic glucose production and skeletal muscle glycogen synthase activity in overweight type II diabetic patients. Metabolism. 1993;42:1217-22.

Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clan Invest. 2001;108:1167-74.

UK prospective diabetes study (UKPDS) group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854-65.

Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R et al. Management of hyperglycaemia 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;29:1963-72.

Chan JC, Deerochanawong C, Shera AS, Yoon KH, Adam JM, Ta VB et al. Role of metformin in the initiation of pharmacotherapy for type 2 diabetes: an Asian-Pacific perspective. Diabetes Res Clin Pract. 2007;75:255-66.

Reasner C, Go¨ke B. Overcoming the barriers to effective glycaemic control for type 2 diabetes. Br J Diab Vasc Dis. 2002;2:290-5.

Vidon N, Chaussade S, Noel M, Franchisseur C, Huchet B, Bernier JJ. Metformin in the digestive tract. Diabetes Res Clin Pract. 1988;4:223-9.

Dunn CJ, Peters DH. Metformin: a review of its pharmacological properties and therapeutic use in noninsulin-dependent diabetes mellitus. Drugs. 1995;49:721-49.

Garber AJ, Duncan TG, Goodman AM, Mills DJ, Rohlf JL. Efficacy of metformin in type II diabetes: results of a double-blind, placebo-controlled, dose-response trial. Am J Med. 1997;103:491-49.

Timmins P, Donahue S, Meeker J, Marathe P. Steady state pharmacokinetics of a novel extended-release metformin formulation. Clin Pharmacokinet. 2005;44:721-9.

Donahue S, Marathe E Guld T, Meeker J. The pharmacokinetics and pharmacodynamics of the metformin extended-release tablet versus immediate-release metformin in subjects with type 2 diabetes. Diabetes. 2002;51:A468.

Corti G, Cirri M, Maestrelli F, Mennini N, Mura P. Sustained-release matrix tablets of metformin hydrochloride in combination with triacetyl- beta-cyclodextrin. Eur J Pharm Biopharm. 2008;68(2):303-9.

Fujioka K, Pans M, Joyal S. Glycemic control in patients with type 2 diabetes mellitus switched from twice-daily immediate-release metformin to a once-daily extended-release formulation. Clin Ther. 2003;25:515-29.

Blonde L, Dailey GE, Jabbour SA, Reasner CA, Mills DJ. Gastrointestinal tolerability of extended-release metformin tablets compared to immediate release metformin tablets: results of a retrospective cohort study. Curr Med Res Opin. 2004;20:565-72.

Krentz AJ, Patel MB, Bailey CJ. New drugs for type 2 diabetes mellitus; what is their place in therapy? Drugs. 2008;68(15):2131-62.

Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R et al. Medical management of hyperglycaemia in type 2 diabetes; a consensus algorithm for the initiation and adjustment of therapy. A consensus statement of the American diabetes association and the European association for the study of diabetes. Diabetes Care. 2009;32(1):193-203.

UK prospective diabetes study 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(9131):837-53.

The diabetes control and complications trial research group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-86.

Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356(24):2457-71.

Levy J, Cobas RA, Gomes MB. Assessment of efficacy and tolerability of once daily extended release metformin in patients with type 2 diabetes mellitus. Diabetol Metabolic Syndrome. 2010;(2):1-6.

Donnelly LA, Morris AD, Pearson ER. Adherence in patients transferred from immediate release metformin to a sustained release formulation: a population-based study. Diabets, Obesity Metabol. 2009;(11):338-42.

Fujioka K, Brazg RL, Raz I, Bruce S, Joyal S, Swanink R et al. Efficacy, dose–response relationship and safety of once-daily extended-release metformin (Glucophage XR) in type 2 diabetic patients with inadequate glycaemic control despite prior treatment with diet and exercise: results from two double-blind, placebo-controlled studies. Diabetes, Obesity Metabol. 2005;7(1):28-39.

Sherwyn D, Vivian F, Bert B, Marilou C, Yukun C, Andrew L. Efficacy, tolerability, and safety of a novel once-daily extended-release metformin in patients with type 2 diabetes. Diabetic Care. 2006;29:759-64.

Bhansali A, Masoodi SR. Efficacy of once- or twice-daily extended release metformin compared with thrice-daily immediate release metformin in type 2 diabetes mellitus. JAPI. 2005;53:441-5.

Gao H, Xiao W, Wang C, Zhaing J, Yang Y, Yang J et al. The metabolic effects of once daily extended-release metformin in patients with type 2 diabetes: a multi centre study. Int J Clin Pract. 2008;62:695-700.

Wulffele MG, Kooy A, Dezeeuw D, Stehouwer CDA, Gansevoort RT. The effect of metformin on blood pressure, blood cholesterol and triglycerides in type 2 diabetes mellitus: a systematic review. J Intern Med. 2004;256:1-14.