Efficacy, Tolerability, and Safety of a Novel Once-Daily Extended-Release Metformin in Patients With Type 2 Diabetes

Abstract

OBJECTIVE -The purpose of this study was to determine the efficacy and safety of a novel extended-release metformin in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS -Adults with type 2 diabetes (newly diagnosed, treated with diet and exercise only, or previously treated with oral diabetic medications) were randomly assigned to receive one of three extended-release metformin treatment regimens (1,500 mg/day q.d., 1,500 mg/day twice daily, or 2,000 mg/day q.d.) or immediate-release metformin (1,500 mg/day twice daily) in a double-blind 24-week trial.RESULTS -Significant decreases (P Ͻ 0.001) in mean HbA 1c (A1C) levels were observed by week 12 in all treatment groups. The mean changes from baseline to end point in the two groups given 1,500 mg extended-release metformin (Ϫ0.73 and Ϫ0.74%) were not significantly different from the change in the immediate-release metformin group (Ϫ0.70%), whereas the 2,000-mg extended-release metformin group showed a greater decrease in A1C levels (Ϫ1.06%; mean difference [2,000 mg extended-release metformin Ϫ immediate-release metformin]: Ϫ0.36 [98.4% CI Ϫ0.65 to Ϫ0.06]). Rapid decreases in fasting plasma glucose levels were observed by week 1, which continued until week 8, and were maintained for the duration of the study. The overall incidence of adverse events was similar for all treatment groups, but fewer patients in the extended-release metformin groups discontinued treatment due to nausea during the initial dosing period than in the immediate-release metformin group. CONCLUSIONS -Once-or twice-daily extended-release metformin was as safe and effective as twice-daily immediate-release metformin and provided continued glycemic control for up to 24 weeks of treatment. Diabetes Care 29:759 -764, 2006M etformin hydrochloride has been widely used as an effective and generally well-tolerated glucoselowering agent for Ͼ40 years and is the most frequently prescribed first-line therapy for patients with type 2 diabetes (1). Metformin typically reduces basal and postprandial hyperglycemia by ϳ25% in Ͼ90% of patients when given alone or with other therapies during a program of managed care (2). In the U.K. Prospective Diabetes Study, intensive glucose control with metformin appeared to reduce the risk of diabetes-related end points in overweight patients and was associated with less weight gain and fewer hypoglycemic attacks than insulin (3).The objective of this study was to evaluate the efficacy, tolerability, and safety of a novel extended-release oral formulation of metformin compared with conventional immediate-release metformin during 24 weeks of double-blind treatment. When administered with food, the extended-release metformin tablet gradually releases drug over 8 h into the upper gastrointestinal tract (4), where metformin is primarily absorbed (5). Prolonged release of metformin from extended-release metformin tablets has been demonstrated in pharmacokinetic studies (6,7). Extended-release metformin showed slightly lower maximum concentrations, longer times to maxi...

Thyreotropin levels in diabetic patients on metformin treatment

“…Metformin is a widely used drug for the treatment of diabetes mellitus, not only in patients with the type 2 disease (7,8) but also in adults and adolescents affected by diabetes mellitus type 1 when insulin resistance is present (9,10).…”

Metformin: clinical use in type 2 diabetes

“…It enables slower drug absorption in the upper GI tract, providing a once-daily dosing option, while also decreasing the frequency and severity of GI side effects [44]. In a randomised, double-blind trial involving 701 participants, the efficacy and safety of the extended-release formulation was found to be similar to the twice-daily immediate release drug [45].…”

Dose-dependent relationship between serum metformin levels and glycemic control, insulin resistance and leptin levels in females newly diagnosed with type 2 diabetes mellitus

“…The present study showed that increasing the initial dose of metformin did not reflect a significant variation in the level of glycemic control in the three patients groups, and such finding was supported by the poor correlation coefficient reported between serum metformin levels and the indicators of glycemic control, although these parameters are significantly improved in all groups. The clinical effects of metformin develop slowly over several days of treatment at least [10] and the range of plasma concentrations over a dosage interval depends upon the formulation without any significant effect on the clinical response [11]. Consequently, one may expect that the C av,ss should provide the best correlate with the clinical and biochemical effects of metformin, the condition which is not clearly demonstrated in the present study; this is not really attributed to the differences in the utilized metformin formulation because the patients included in the study were supplied by the same type of formulation to avoid discrepancies in this respect.…”

“…Moreover, the bioavailability of metformin is not complete, and large interindividual differences in bioavailability after oral administration in the range of 20% -70% have been described [9]. The clinical effects of metformin develop slowly over several days of treatment at least [10] and the range of plasma concentrations over a dosage interval depends upon the formulation without any significant effect on the clinical response [11]. The present study was designed to evaluate the dose-response relationship between serum metformin levels and glycemic control, insulin resistance and leptin levels in females newly diagnosed with type 2 diabetes.…”