Efficacy, tolerability, and safety of a novel once-daily extended-release metformin in patients with type 2 diabetes
ABSTRACT The purpose of this study was to determine the efficacy and safety of a novel extended-release metformin in patients with type 2 diabetes.
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.
Significant decreases (P < 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 (-0.73 and -0.74%) were not significantly different from the change in the immediate-release metformin group (-0.70%), whereas the 2,000-mg extended-release metformin group showed a greater decrease in A1C levels (-1.06%; mean difference [2,000 mg extended-release metformin - immediate-release metformin]: -0.36 [98.4% CI -0.65 to -0.06]). 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.
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.
- SourceAvailable from: Chien-Hsing Lee[Show abstract] [Hide abstract]
ABSTRACT: Both slow-release (SR) and regular-release (RR) metformin were effective in the treatment of type 2 diabetes mellitus. We compare the efficacy, safety, and effects on serum adipocytokines and inflammatory markers of both regimens in patients with type 2 diabetes mellitus. A prospective, randomized, double-blind study enrolled 55 patients with type 2 diabetes mellitus, which were randomly assigned to receive either metformin SR or RR (at a maximal dosage of 2000 mg/d for 12 weeks). Glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose, adipocytokines, C-reactive protein, and insulin resistance and pancreatic beta-cell function were measured before and after treatment. Significant decreases (P<.001) in mean HbA1c and fasting plasma glucose levels were observed in each group. However, the mean changes in HbA1c from baseline to end point in the 2 groups were not significantly different. Changes in metabolic parameters were similar except that a decreased total cholesterol level was observed in the metformin RR group. Neither regimen treatment had any influence on insulin resistance, but metformin RR improved beta-cell function. Neither regimen had an effect on serum adipocytokines or inflammatory markers. Once-daily metformin SR was as safe and effective as metformin RR in type 2 diabetic patients. Neither dosage form affected serum adipocytokines and inflammatory markers.Metabolism 09/2007; 56(8):1087-92. DOI:10.1016/j.metabol.2007.03.018 · 3.61 Impact Factor
Article: Metformin Extended Release[Show abstract] [Hide abstract]
ABSTRACT: ▴ Metformin extended release (metformin ER) is a novel gastric-retentive formulation of the antihyperglycemic agent that can be administered once daily. The polymer matrix of the metformin ER 500mg tablet swells in gastric fluid, causing it to be retained in the stomach in the fed state. Over a period of ≊8 hours, the drug dissolves and diffuses through the matrix to be absorbed in the upper gastrointestinal tract. ▴ Systemic exposure to the drug (assessed by the area under the plasma concentration-time curve) with oral metformin ER 1000mg once daily did not differ from that of immediate-release metformin (metformin IR) 1000 mg/day administered as a divided dose. However, the time to maximum plasma concentration was 7.5 hours with metformin ER versus 4.2 hours with metformin IR.▴ Glycemic control, measured by change from baseline in mean glycosylated hemoglobin (HbA1c) levels at study endpoint, with metformin ER 1500 mg/day (once daily or as divided doses morning and night) or 2000 mg/day (once daily) did not differ from that with metformin IR 1500 mg/day as a divided dose in a 24-week, double-blind, randomized trial in 706 patients with type 2 diabetes mellitus. ▴ In the same study, the American Diabetes Association-recommended HbA1c level of <7% was achieved in significantly more metformin ER 2000 mg/day than metformin IR 1500 mg/day recipients.▴ Greater glycemic control was seen with metformin ER 1500-2000 mg/day plus glyburide (glibenclamide) than with glyburide plus placebo in a 24-week, double-blind, randomized trial in 575 patients with type 2 diabetes. ▴ Metformin ER is generally well tolerated, with an adverse event profile similar to that of metformin IR. Of interest, the incidence of nausea was significantly lower with metformin ER than with metformin IR in the first week of treatment, suggesting that more rapid dose titration may be possible with metformin ER. The incidence of adverse events with metformin ER 2000 mg/day did not differ from that with metformin IR 1500 mg/day.American Journal of Drug Delivery 12/2005; 4(3):177-186. DOI:10.2165/00137696-200604030-00005
Article: Prolonged-Release Ciprofloxacin[Show abstract] [Hide abstract]
ABSTRACT: ▴ Prolonged-release ciprofloxacin (ciprofloxacin PR) is a novel oral formulation of the fluoroquinolone antibacterial that allows once-daily administration. The polymeric matrix of the tablet particles swells so that the particles are retained in the fed stomach. The particles erode on contact with gastric acid, releasing approximately 90% of a 500mg ciprofloxacin PR dose at a near constant rate to the upper gastrointestinal tract over a 6-hour period.▴ The bactericidal activity of ciprofloxacin PR is similar to that of immediate-release ciprofloxacin (ciprofloxacin IR). Both formulations showed similar in vitro activity against common uropathogens, including Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. In patients with ciprofloxacin-susceptible uncomplicated urinary tract infections, bacterial eradication rates for each of these uropathogens were similar with ciprofloxacin PR or ciprofloxacin IR.▴ Oral ciprofloxacin PR 500mg once daily produces similar systemic exposure to that of ciprofloxacin IR 250mg twice daily, but the time to maximum plasma concentration is prolonged and the initial peak in drug concentration is higher than with ciprofloxacin IR. A similar pattern is seen in terms of urinary excretion. Other pharmacokinetic parameters are similar to those of ciprofloxacin IR.▴ In 523 evaluable women with ciprofloxacin-susceptible uncomplicated urinary tract infection, 3 days' treatment with ciprofloxacin PR 500mg once daily had similar efficacy to ciprofloxacin IR 250mg twice daily. Initial bacterial eradication rates were ≥90% and initial clinical cure rates were ≥86% for either formulation. ▴ Ciprofloxacin PR was well tolerated in clinical trials in women with acute cystitis. Fungal infection (mostly vaginal yeast infection) was the most common adverse event possibly related to ciprofloxacin PR treatment. A tolerability advantage for ciprofloxacin PR over ciprofloxacin IR was seen in terms of nausea and diarrhea, which occurred significantly less often with ciprofloxacin PR.American Journal of Drug Delivery 12/2005; 4(2):113-120. DOI:10.2165/00137696-200604020-00007