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Comparison of Treatment Persistence with Two Formulations of Metformin
Hankin C1, Berner B2, Wu J2, Bronstone A1, Wang Z1
(1) BioMedEcon, LLC, South San Francisco, CA, (2) Depomed, Inc., Menlo Park, CA ABSTRACT
OBJECTIVES
Purpose: Evidence shows that tight glycemic control mitigates the adverse microvascular and
We sought to answer the following questions: macrovascular effects of diabetes. Metformin, an oral anti-hyperglycemic agent, is commonly Baseline Characteristics
% of Patients Achieving ADA Target A1C (< 7%)
prescribed as first-line treatment for type 2 diabetes. Despite metformin's demonstrated efficacy, • Are there differences in persistence rates associated with immediate-release metformin MER2000Q
low rates of treatment persistence (the proportion of patients remaining on medication for a period (MIR) versus a novel extended-release metformin (MER) formulation? of time) are typical among diabetes patients.1 We examined persistence rates associated with immediate-release metformin (MIR) versus a novel extended-release metformin (MER) • If there are differences in persistence, do these differences affect A1C outcomes? 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- This was a multicenter, randomized, double-blind (double-dummy), active-controlled, dose- 2000Q)]. Participants were adults with type 2 diabetes who were medication naïve or received ranging, non-inferiority, parallel-group clinical study designed to compare the efficacy and safety patients
achieved
patients
prior oral hypoglycemic monotherapy. Titration to study dose was achieved over 3 weeks. of a novel metformin extended-release (MER) formulation at doses of 1500 once daily achieved ADA
ADA target
Analyses were conducted using a modified intent-to-treat (ITT) approach, whereby participants target A1C <
(MER1500Q), 500 mg in the morning and 1000 mg in the evening (MER1500 B), and 2000 once A1C < 7% *
who completed the study titration phase, received one week of study dose, and had at least one daily (MER 2000Q), to immediate-release metformin 500 mg in the morning and 1000 mg in the A1C follow-up from baseline were included. Reasons for study withdrawal (initiated by investigator or patient) included lack of efficacy, serious or non-serious adverse events, death, Med cal Ch
cal C aracter
acter tics
patient desire to withdraw, patient noncompliance with protocol, and lost to follow-up. Patients The MIR dosage was chosen because it is the most commonly used dosage of metformin and is who prematurely terminated for any reason were defined as non-persistent; those who were accepted as being safe and effective with a tolerable side effect profile. The MIR dose regimen A1C Levels
* p = 0.0096
titrated to the full study dose and completed the study through week 24 were considered to be used was as described in the product insert. * ITT=Intent to Treat, LOCF = Last observation carried forward Source: Data on File, Trial 003, Depomed, Inc. The MER1500Q and MER 1500B dosages were chosen to examine the possible advantages of Results: The ITT analysis included 647 participants with a mean baseline A1C of 8.3% (SD 1.5).
once-daily vs. twice-daily doses of MER at a comparable dose to that of the control group. The Treatment groups had similar demographics and disease-related characteristics at baseline. MER2000Q dose was designed to compare the safety and efficacy of this higher dosage to the Patients who received MER-2000Q were approximately half as likely to prematurely terminate Premature Termination by Metformin Treatment Group
CONCLUSIONS
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%) We report persistency and efficacy results of the highest MER dose (MER 2000Q) versus the MIR Significantly fewer subjects in the MER
• Superior efficacy, as demonstrated by a significantly greater compared with those receiving MIR-1500B (9.9%, NS) and MER-1500Q (11.4%, p=0.03). Groups 2000Q group dropped out due to
percentage of patients achieving A1C at the ADA target of < 7%, was were similar with respect to the number, type, and severity of adverse events. adverse events or lack of treatment
Participants were adults with type 2 diabetes who were drug naïve or previously treated with anti- efficacy (5.3% vs 13.8%, p=0.007).
Conclusions: Higher treatment persistence is associated with better glycemic control and lower
Dropouts Due to AEs or Lack of Efficacy
• The higher dose of MER 2000Q appears to have been well tolerated. healthcare costs.2 Persistence rates were two times higher with extended-release versus immediate-release metformin, possibly due to enhanced tolerability and/or efficacy associated • Persistence rates were two times higher with extended-release versus with the maximum Glumetza 2000 mg QD dose. Figure 1. Study Design
immediate-release metformin, possibly due to enhanced tolerability and/or efficacy associated with higher dose.
BACKGROUND
Diabetes mellitus is a metabolic disorder characterized by the presence of chronic hyperglycemia REFERENCES
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PRESENTED AT THE 28th ANNUAL MEETING OF THE SOCIETY FOR MEDICAL DECISION MAKING, CAMBRIDGE, MA, OCTOBER 14-18, 2006.

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