DOSE COMPARISON AND SIDE EFFECT PROFILE OF METFORMIN EXTENDED RELEASE VERSUS METFORMIN IMMEDIATE RELEASE
AbstractBackground: Diabetes Mellitus type 2 is very common worldwide, with majority of cases in Asia Pacific region. Metformin is the first line therapy, along with lifestyle modification for all type 2 diabetics as recommended by ADA. Metformin is available as conventional Metformin Immediate Release (MIR) and Metformin Extended Release (MXR). Metformin XR has better gastrointestinal tolerability and fewer side effects as compared to Metformin IR, with similar efficacy regarding anti-hyperglycaemic effects. The objective of this study was to determine whether metformin XR is as effective as Metformin IR in maintaining glycaemic control at equivalent doses or even at reduced doses; and to compare the side effect profile of the two preparations. Methods: This randomized control trial was conducted at Medical and Endocrinology OPD of Jinnah Hospital Lahore A total of 90 type 2 diabetics of both genders were recruited using nonprobability purposive sampling. Patients were randomized into 3 groups; 30 in each group. Group 1 received Metformin IR 1000 mg twice daily; group 2 received metformin XR 1000mg twice daily; and group 3 received metformin XR 500 mg twice daily, for a period of three months. HbA1c was done at baseline and after three months of therapy along with fasting blood sugars and random blood sugars weekly. Results: The mean age of patients was 46±9 years, with 54% being males and 46% being females. There was a 1% reduction in HbA1c in group 1, 0.7% reduction in group 2 and only 0.4% reduction in group 3. Similarly, all three therapies were equally effective in reducing blood sugar fasting and blood sugar random at three months. Side effects namely diarrhoea, dyspepsia and flatulence were greatest with Metformin IR (40%) but less than half with Metformin XR at equivalent dose and negligible at half the dose. Conclusions: All three Metformin groups were effective in reduction of HbA1C and glycaemic control clinically and there is no statistical difference in HbA1c reduction among groups at three months.Keywords: Diabetes Mellitus type 2, Metformin, Immediate release; Metformin extended release, Efficacy; Side effects
Melmed S, PolonskyKS, Larsen PR, Kronenberg HM. Williams Textbook of Endocrinology. 12th ed. Philadelphia: Elsevier Saunders 2011;1371–1435.
Yoon KH, Lee JH, Kim JW, Cho JH, Choi YH, Ko SH, et al. Epidemic obesity and type 2 diabetes in Asia. Lancet 2006;368(9548):1681–8.
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes. Estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27(5):1047–53.
Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world: A growing challenge. N Engl J Med 2010;356(3):213–5.
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(3):255–66.
WHO. Preventing Chronic Diseases: A Vital Investment. World Health Organization; 2005.
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 Obes Metab 2005;7(1):28–39.
Davidson J, Howlett H. New prolonged-release metformin improves gastrointestinal tolerability. Br J Diabetes Vasc Dis 2004;4(4):273–7.
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(4):565–72.
Kim CH, Han KA, Oh HJ, Tan KE, Sothiratnam R, Tjokroprawiro A, et al. Safety, tolerability and efficacy of Metformin extended release oral anti diabetic therapy in patients with type II diabetes: an observational trial in Asia. J Diabetes 2012;4(4):395–406.
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(2):515–29.
Marathe E, Turner K. Steady-state pharmacokinetics of the metformin extended release tablet versus the immediate-release metformin tablet in healthy subjects. Diabetes 2002;51:A474.
Gusler G, Gorsline J, Levy G, Zhang SZ, Weston IE, Naret D, et al. Pharmacokinetics of metformin gastric-retentive tablets in healthy volunteers. J Clin Pharmacol 2001;41(6):655–61.
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(6):491–7.
Timmins P, Donahue S, Meeker J, Marathe P. Steady-state pharmacokinetics of a novel extended-release metformin formulation. Clin Pharmacokinet 2005;44(7):721–9.
Feher MD, Al-Mrayat M, Brake J, Leong KS. Tolerability of prolonged-release metformin (Glucophage® SR) in individuals intolerant to standard metformin: Results from four UK centres. Br J Diabetes Vasc Dis 2007;7(5):225–8.
Gao H, Xiao W, Wang C, Zhang J, Yang Y, Yang W, et al. The metabolic effects of once daily extended-release metformin in patients with type 2 diabetes: A multicentre study. Int J Clin Pract 2008;62(5):695–700.
Swartz S, Fonseca V, Berner B, Cramer M, Chiang YK, Lewin A. Efficacy,tolerability and safety of a novel once daily extended release Metformin in patients with type II diabetes. Diabetes Care 2006;29(4):4759–64.
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. J Assoc Physicians India 2005;53:441–5.
Donelly LA, Morris AD, Pearson ER. Adherence in patients transferred from immediate release metformin to a sustained release formulaton: a population based study. Diabetes Obes Metab 2009;11(4):338–42.
Journal of Ayub Medical College, Abbottabad is an OPEN ACCESS JOURNAL which means that all content is FREELY available without charge to all users whether registered with the journal or not. The work published by J Ayub Med Coll Abbottabad is licensed and distributed under the creative commons License CC BY ND Attribution-NoDerivs. Material printed in this journal is OPEN to access, and are FREE for use in academic and research work with proper citation. J Ayub Med Coll Abbottabad accepts only original material for publication with the understanding that except for abstracts, no part of the data has been published or will be submitted for publication elsewhere before appearing in J Ayub Med Coll Abbottabad. The Editorial Board of J Ayub Med Coll Abbottabad makes every effort to ensure the accuracy and authenticity of material printed in J Ayub Med Coll Abbottabad. However, conclusions and statements expressed are views of the authors and do not reflect the opinion/policy of J Ayub Med Coll Abbottabad or the Editorial Board.
USERS are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author. This is in accordance with the BOAI definition of open access.
AUTHORS retain the rights of free downloading/unlimited e-print of full text and sharing/disseminating the article without any restriction, by any means including twitter, scholarly collaboration networks such as ResearchGate, Academia.eu, and social media sites such as Twitter, LinkedIn, Google Scholar and any other professional or academic networking site.