COMPARISON OF TREATMENT PERSISTENCE WITH TWO FORMULATIONS OF METFORMIN
Cheryl S. Hankin, PhD1, Bret Berner, PhD2, Jacqueline Wu, PhD2, Amy Bronstone, PhD1, and Zhaohui Wang, MS1. (1) BioMedEcon, LLC, South San Francisco, CA, (2) Depomed, Inc., Menlo Park, CA
Purpose: Evidence shows that tight glycemic control mitigates the adverse microvascular and macrovascular effects of diabetes. Metformin, an oral anti-hyperglycemic agent for type 2 diabetes, is commonly prescribed as first-line treatment for type 2 diabetes. Despite metformin's demonstrated efficacy, low rates of treatment persistence (the proportion of patients remaining on medication for a period of time) are common among diabetes patients. We examined persistence rates associated with immediate-release metformin (MIR) versus a novel extended-release metformin (MER) formulation designed to improve tolerability and efficacy. Methods: The study was a phase III, 24-week, randomized, double-blind, active-controlled, fixed-dose trial comparing MIR 1500 mg/day, b.i.d. (MIR-1500B) versus MER at three doses [1,500 mg/day q.d. (MER-1500Q), 1,500 mg/day b.i.d. (MER-1500B), or 2,000 mg/day q.d. (MER-2000Q)]. Participants were adults with type 2 diabetes who were medication na´ve or received prior oral hypoglycemic monotherapy. Titration to study dose was achieved over 3 weeks. Analyses were conducted using a modified intent-to-treat (ITT) approach, whereby participants who completed the study titration phase, received one week of study dose, and had at least one A1C follow-up from baseline were selected. Reasons for study withdrawal (initiated by investigator or patient) included lack of efficacy, serious or non-serious adverse events, death, patient desire to withdraw, patient noncompliance with protocol, and lost to follow-up. Patients who prematurely terminated for any reason were defined as non-persistent; those who were titrated to the full study dose and completed the study through week 24 were considered to be persistent. Results: The ITT analysis included 647 participants with a mean baseline A1C of 8.3% (SD 1.5). Treatment groups had similar demographics and disease-related characteristics at baseline. Patients who received MER-2000Q were approximately half as likely to prematurely terminate from the study as those receiving MIR-1500B (Odds Ratio: 0.52, 95% CI 0.28 to 0.96, p=0.04). Patients receiving MER-2000Q had a lower rate of withdrawal due to lack of efficacy (1.8%) compared with those receiving MIR-1500B (9.9%, NS) and MER-1500Q (11.4%, p=0.03). Groups were similar with respect to the number, type, or severity of adverse events. Conclusions: Higher treatment persistence is associated with better glycemic control. Persistence rates were two times higher with extended-release versus immediate-release metformin, possibly due to enhanced tolerability and/or efficacy associated with the maximum Glumetza 2000 mg QD dose.