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.
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ABSTRACT: Diabetes Mellitus is the most common endocrine disorder and metformin is the most commonly prescribed oral hypoglycemic agent. Metformin is well known to cause viamin B12 deficiency due to effect on calcium-dependent membrane action in the terminal ileum leading to malabsorption of vitamin B12. The purpose of this study is to determine prevalence and associations of Vitamin B12 deficiency in patients of type 2 diabetes mellitus treated with metformin. This case control study was carried out in department of medicine, Combined Military Hospital, Kharian from 1(st) Jan 2012 to 30 december 2012. We enrolled 114 outdoor patients of type 2 diabetes mellitus currently on metformin for atleast 12 months, by consecutive sampling, and 105 age and sex matched patients taken as control. Patients with vitamin B12 levels of less than 150 pg/ml were said to be B12 deficient. The results were analyzed on SPSS version 16. Serum B12 levels were low in 35 patients (31%) on metformin as compared to only 9 patients (8.6%) among controls,(p value 0.002). Mean B12 levels were significantly low in metformin group 311 pg/ml (±194.4), p value 0.03. Dose of metformin had inverse correlation with B12 levels and the difference was statistically significant with p-value < 0.001. Our study demonstrated significantly high prevalence of vitamin B12 deficiency in patients treated with metformin with significant effect of dose and duration of metformin use on B12 levels. Physicians must recognize this important fact and screen diabetics on metformin therapy for underlying B12 deficiency.10/2013; 16:67. DOI:10.11604/pamj.2013.16.67.2800
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ABSTRACT: As inhibitors of organic cation transporters (OCTs), proton pump inhibitors (PPIs) may affect the plasma levels of metformin, an OCT substrate. We investigated the effects of two PPIs, pantoprazole and rabeprazole, on metformin pharmacokinetics and glucose levels in healthy subjects. In this open, randomized, 6 × 3 cross-over study, 24 participants were administered metformin, either alone or in combination with pantoprazole or rabeprazole. The plasma concentrations of metformin and serum concentrations of glucose after a 75 g oral glucose tolerance test (OGTT) were determined. The area under the concentration-time curve (AUC) for metformin was 15% and 16% greater following co-administration with pantoprazole and rabeprazole, respectively. The maximum plasma metformin concentrations (Cmax) also increased by 15% and 22%, respectively, compared to when it was administered without the PPIs. The percentage change in the AUC for glucose concentration versus time for metformin plus rabeprazole was significantly lower than that for metformin plus pantoprazole (geometric mean ratio: 0.96 [90% CI: 0.92 - 0.99] and 0.77 [0.63 - 0.93], respectively). There was no significant difference in the maximum glucose concentration. In conclusion, concomitant administration of PPIs with metformin significantly increased plasma metformin exposure, but the effects on glucose disposition were minor and varied depending on the PPI administered.Drug metabolism and disposition: the biological fate of chemicals 04/2014; 42(7). DOI:10.1124/dmd.113.055616 · 3.74 Impact Factor
Article: Metformin and Thyroid: An Update.[Show abstract] [Hide abstract]
ABSTRACT: Metformin is one of the most widely prescribed antidiabetic medications with a favorable safety profile. In the last decade, several studies have reported a TSH-lowering effect of metformin in patients with diabetes mellitus. To review literature data on the role of metformin use on thyroid function tests and the course of thyroid cancer. WE PERFORMED A SEARCH IN THE PUBMED DATABASE USING THE TERMS: 'metformin', 'thyroid', 'TSH', 'diabetes', 'polycystic ovarian syndrome (PCOS)' and 'thyroid cancer'. The majority of available evidence suggests that metformin therapy results in a modest reduction of TSH levels in diabetic and/or PCOS patients with thyroid disorder, while thyroid hormone levels remain unaltered. It appears that this effect is independent of thyroid autoimmunity and thyroxine treatment. However, metformin use in subjects with an intact thyroid axis is not associated with a significant change of TSH levels. Concerning thyroid cancer, there is experimental evidence showing antimitogenic properties of metformin in differentiated and medullary thyroid cancer cells. On the other hand, there is also data supporting that metformin administration inhibits iodine uptake by thyroid cells and thus may limit the effectiveness of radioactive iodine treatment. Most studies suggest a TSH suppressive action of metformin in subjects with overt or subclinical thyroid dysfunction, while this is not apparent in euthyroid individuals. It appears that metformin has antimitogenic properties against various thyroid cancer types; however, experimental evidence of reduced efficacy of radioactive iodine treatment following metformin administration may limit its use in the management of differentiated thyroid cancer.03/2013; 2(1):22-28. DOI:10.1159/000346248