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Comparison of adjunctive therapy with metformin and acarbose in patients with Type-1 diabetes mellitus.

ABSTRACT: All the aforementioned data have stimulated interest in studying other potential therapies for T1DM including noninsulin pharmacological therapies. The present study attempts to investigate the effect of adjunctive therapy with metformin and acarbose in patients with Type-1 diabetes mellitus.In a single-center, placebo-controlled study (IRCT201102165844N1) we compared the results of two clinical trials conducted in two different time periods on 40 patients with Type-1 diabetes mellitus. In the first section, metformin was given to the subjects. After six months, metformin was replaced with acarbose in the therapeutic regimen. In both studies, subjects were checked for their BMI, FBS, HbA1C, TGs, Cholesterol, LDL, HDL, 2hpp, unit of NPH and regular insulin variations.Placebo-controlled evaluation of selected factors has showna significant decrease in FBS and TG levels in the metformin group during follow up but acarbose group has shown substantial influence on two hour post prandial (2hpp) and regular insulin intake decline. Moreover, Comparison differences after intervention between two test groups has shown that metformin has had superior impact on FBS and HbA1C decline in patients. Nonetheless, acarbose treatment had noteworthy influence on 2hpp, TGs, Cholesterol, LDL, and regular insulin intake control.The results of this experiment demonstrate that the addition of acarbose or metformin to patients with Type-1 diabetes mellitus who are controlled with insulin is commonly well tolerated and help to improve metabolic control in patients.

SUBMITTER: Ziaee A

PROVIDER: S-EPMC5510127 | biostudies-other | 2017 May-Jun

REPOSITORIES: biostudies-other

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Project description:UNLABELLED:Metformin, a biguanide derivate, has pleiotropic effects beyond glucose reduction, including improvement of lipid profiles and lowering microvascular and macrovascular complications associated with type 2 diabetes mellitus (T2DM). These effects have been ascribed to adenosine monophosphate-activated protein kinase (AMPK) activation in the liver and skeletal muscle. However, metformin effects are not attenuated when AMPK is knocked out and intravenous metformin is less effective than oral medication, raising the possibility of important gut pharmacology. We hypothesized that the pharmacology of metformin includes alteration of bile acid recirculation and gut microbiota resulting in enhanced enteroendocrine hormone secretion. In this study we evaluated T2DM subjects on and off metformin monotherapy to characterize the gut-based mechanisms of metformin. Subjects were studied at 4 time points: (i) at baseline on metformin, (ii) 7 days after stopping metformin, (iii) when fasting blood glucose (FBG) had risen by 25% after stopping metformin, and (iv) when FBG returned to baseline levels after restarting the metformin. At these timepoints we profiled glucose, insulin, gut hormones (glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY) and glucose-dependent insulinotropic peptide (GIP) and bile acids in blood, as well as duodenal and faecal bile acids and gut microbiota. We found that metformin withdrawal was associated with a reduction of active and total GLP-1 and elevation of serum bile acids, especially cholic acid and its conjugates. These effects reversed when metformin was restarted. Effects on circulating PYY were more modest, while GIP changes were negligible. Microbiota abundance of the phylum Firmicutes was positively correlated with changes in cholic acid and conjugates, while Bacteroidetes abundance was negatively correlated. Firmicutes and Bacteroidetes representation were also correlated with levels of serum PYY. Our study suggests that metformin has complex effects due to gut-based pharmacology which might provide insights into novel therapeutic approaches to treat T2DM and associated metabolic diseases. TRIAL REGISTRATION:www.ClinicalTrials.gov NCT01357876.

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Comparison of adjunctive therapy with metformin and acarbose in patients with Type-1 diabetes mellitus.

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