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MARCH2: comparative assessment of therapeutic effects of acarbose and metformin in newly diagnosed type 2 diabetes patients.

ABSTRACT: The data of MARCH (Metformin and AcaRbose in Chinese as the initial Hypoglycaemic treatment) trial demonstrated that acarbose and metformin have similar efficacy as initial therapy for hemoglobin A1c (HbA1c) reduction in Chinese patients with newly diagnosed type 2 diabetes. We investigated whether the therapeutic efficacy was diversified under different body mass index (BMI) status.All 784 subjects were divided into normal-weight group (BMI<24 kg/m2), overweight group (BMI 24-28 kg/m2) and obese group (BMI≥28 kg/m2). Patients were assigned to 48 weeks of therapy with acarbose or metformin, respectively. The clinical trial registry number was ChiCTR-TRC-08000231.The reduction of HbA1c levels and the proportion of patients with HbA1c of 6.5% or less were similar in the three groups after acarbose and metformin treatment. In overweight group, fasting blood glucose (FBG) after metformin treatment showed greater decline compared to acarbose group at 48 weeks [-1.73 (-1.99 to -1.46) vs. -1.37 (-1.61 to -1.12), P<0.05), however the decrease of 2 h post-challenge blood glucose (PBG) after acarbose treatment at 48 weeks was bigger compared to metformin group [-3.34 (-3.83 to-2.84) vs. -2.35 (-2.85 to -1.85), P<0.01]. Both acarbose and metformin treatment resulted in a significant decrease in waist circumference, hip circumference, weight and BMI in the three groups (all P<0.05).Acarbose and metformin decreased HbA1c levels similarly regardless of BMI status of Chinese type 2 diabetic patients. Acarbose and metformin resulted in a significant and modest improvement of anthropometric parametres in different BMI status. Thus, acarbose treatment may contribute a similar effect on plasma glucose control compared to metformin, even in obesity patients.ChiCTR.org ChiCTR-TRC-08000231.

SUBMITTER: Wang G

PROVIDER: S-EPMC4141807 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Project description:BackgroundDiabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). Metformin, which is an essential anti-diabetic drug, has been shown to exhibit anti-TB effects in patients with DM. Its effect on preventing the development of TB among patients who are newly diagnosed with DM remains unclear.MethodsThis was a retrospective cohort study using the claims database of the Korean Health Insurance Review and Assessment Service. The study population included patients who were newly diagnosed with type 2 DM and who were treated with anti-diabetic drugs between 1 January 2003 and 31 March 2011. A patient was defined as a metformin user if he/she had taken metformin for more than 28 days within 6 months since cohort entry, and as a metformin non-user if he/she had never been treated with metformin. The development of TB within 2 years after the index date was compared by Cox proportional hazard regression models between metformin users and 1:1 propensity score (PS)-matched non-users.ResultsAmong 76,973 patients who were newly diagnosed with type 2 DM, 13,396 were classified as metformin users, 52,736 were classified as metformin non-users, and 10,841 were excluded from the final analysis. PS-matched Cox proportional hazard regression models revealed that metformin use was not associated overall with the prevention of TB development (HR 1.17; 95% CI 0.75-1.83; P = 0.482). There was a trend, however, towards a reduction in the development of TB among patients taking a higher cumulative dose of metformin. Patients who were in the highest quartile (Q4) of cumulative metformin dose had only a 10% risk of developing TB compared to metformin non-users. In contrast, during the early phases of metformin treatment, patients in the second quartile (Q2) of cumulative metformin use had a higher risk of developing TB than patients in the first quartile (Q1).ConclusionsOnly the highest cumulative doses of metformin were protective against the development of TB among patients who were newly diagnosed with type 2 DM; lower cumulative doses of metformin did not appear to reduce the incidence of active TB infection.

Project description:BackgroundThe study was conducted to investigate the effects of metformin treatment on the human gut microbiome's taxonomic and functional profile in the Latvian population, and to evaluate the correlation of these changes with therapeutic efficacy and tolerance.MethodsIn this longitudinal observational study, stool samples for shotgun metagenomic sequencing-based analysis were collected in two cohorts. The first cohort included 35 healthy nondiabetic individuals (metformin dose 2x850mg/day) at three time-points during metformin administration. The second cohort was composed of 50 newly-diagnosed type 2 diabetes patients (metformin dose-determined by an endocrinologist) at two concordant times. Patients were defined as Responders if their HbA1c levels during three months of metformin therapy had decreased by ≥12.6 mmol/mol (1%), while in Non-responders HbA1c were decreased by <12.6 mmol/mol (1%).ResultsMetformin reduced the alpha diversity of microbiota in healthy controls (p = 0.02) but not in T2D patients. At the species level, reduction in the abundance of Clostridium bartlettii and Barnesiella intestinihominis, as well as an increase in the abundance of Parabacteroides distasonis and Oscillibacter unclassified overlapped between both study groups. A large number of group-specific changes in taxonomic and functional profiles was observed. We identified an increased abundance of Prevotella copri (FDR = 0.01) in the Non-Responders subgroup, and enrichment of Enterococcus faecium, Lactococcus lactis, Odoribacter, and Dialister at baseline in the Responders group. Various taxonomic units were associated with the observed incidence of side effects in both cohorts.ConclusionsMetformin effects are different in T2D patients and healthy individuals. Therapy induced changes in the composition of gut microbiome revealed possible mediators of observed short-term therapeutic effects. The baseline composition of the gut microbiome may influence metformin therapy efficacy and tolerance in T2D patients and could be used as a powerful prediction tool.

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MARCH2: comparative assessment of therapeutic effects of acarbose and metformin in newly diagnosed type 2 diabetes patients.

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