The Relationship Between Baseline Body Mass Index And Blood Glucose Control With Metformin Therapy(1500Mg) In T2DM

BACKGROUND:It is demonstrated by some big studies in American, Europe and Asian regions, there is no difference in the normal weight, overweight and obese groups, Based on BMI 2007 guideline, about 30%-40% are normal weight population. And China has no efficacy evidence on normal weight population and also in clinical practice there is concern of weight excess loss in normal weight population with Metformin therapy. The study will put 1500mg treatment group as the target population in analysis, because it is considered that in the real clinical practice, a large part of T2DM patients take 1500mg Metformin as maximum dosage. The result will be helpful to real clinical practice as evidence. OBJECTIVE: The primary efficacy objective of this study is to investigate the effect of the baseline body mass index (BMI) on the response to Metformin monotherapy on glycemic control in Chinese patients with newly diagnosed T2DM. METHOD:The study is designed as an open-label, with 16 weeks Metformin XR treatment duration trial, to investigate the effect of the baseline body mass index (BMI) on the response to Metformin XR monotherapy in glycemic control in Chinese patients with newly diagnosed T2DM by examining the relationship between baseline BMI and HbA1c reduction after a 16-week oral administration of Glucophage XR (calculated as Week 16 HbA1c-baseline HbA1c) in Chinese patients with newly diagnosed T2DM. Based on their baseline BMI, eligible subjects will be enrolled to the 3 BMI subgroups in a 1:1:1 ratio. The BMI subgroups are defined according to the Chinese guideline 2007:Obese is defined as BMI≥28kg/m2, overweight is defined as BMI≥24kg/m2 and <28kg/m2, normal weight is defined as BMI≥18.5kg/m2 and <24kg/m2. Each subgroup will contain 69 subjects, including 10% of drop-out rate. Metformin XR will be administered to subjects enrolled to the study for 16 weeks. The initial dose will be 500mg/day orally taken once daily with the evening meal, and then it will be up-titrated by increments of 500mg weekly to 1500mg/day unless intolerance or hypoglycemia occurs. At week 4 and afterwards, the maximum daily dose may be 2000mg/day (orally, once daily, with the evening meal), if FPG>7.0mmol/L (126mg/dL). The patients will be followed every 4 weeks. Efficacy data collected:HbA1c at baseline and week 16, and FPG at baseline, week 4, week 8, week 12 and week 16. Safety data collected:adverse events will be collected at every 4 weeks, and will be evaluated if it is related to Metformin or not. Statistics:Assuming the standard deviation for the changes from baseline in HbA1c maximally is 1.0 across the baseline BMI subgroups envisaged,62 patients for a single subgroup will be sufficient to estimate the mean change in HbA1c with a precision of 0.25% within the subgroup. Given the number of baseline BMI subgroups and given that no correction for reason of multiplicity will be made to the 95% confidence level within each BMI subgroup, consider 10% drop-out, the total sample size is 207. ANNOVA is used for efficacy analysis. SPSS 16.0 is used in this study. RESULT:251 patients were enrolled into the study with 1500mg treatment group (normal weight arm:85, overweight arm:84 and obese arm:82). 74,77,75/76,77,76 in normal weight arm, overweight arm and obese arm respectively completed the study/enrolled into FAS. Efficacy result:in 1500mg treatment population, HbA1c(%) mean decrease at week 16, were 1.97,1.87 and 1.76 in normal weight arm, overweight arm and obese arm respectively. There is no significant difference in 3 arms (p=0.330). FPG(mmol/L) decrease at week 16 were 1.896,2.041,1.802 in normal weight arm, overweight arm and obese arm respectively, and there is no significant difference in 3 arms (p=0.742). BMI(mean) at week 16 is 21.96kg/m2, decreased 0.53 kg/m2 compared to baseline. Safety: Major AEs related to drug were Diarrhea. CONCLUSION:In 1500mg treatment group of this study, Metformin has a significant benefit of glycemic control, there is no different on glycemic control with Metformin monotherapy in different baseline BMI subgroups, and there is no risk of excess weight loss in normal weight group. Safety and tolerance of Metformin are good.