A systematic review and meta-analysis assessing effects of metformin monotherapy on glycemic control and weight in drug-naive patients with type 2 diabetes mellitus (T2DM) included 16 studies (n=1140). Compared to placebo, metformin monotherapy was associated with decreased glycosated hemoglobin (HbA1c) by 0.95% at 3 months (95% CI 0.50 to 1.39; I²=87%) and 1.32% at 6 months (95% CI 1.01 to 1.62; I²=71%), and decreased fasting plasma glucose by 1.92mmol/L at 1 month (95% CI 0.11 to 3.74, I²=88%), 1.79mmol/L at 3 months (95% CI 0.92 to 2.66, I²=88%) and 2.14mmol/L at 6 months (95% CI 1.17 to 3.12; I²=82%). No significant difference was demonstrated for the comparisons of weight due to relatively small number of studies retrieved.
A population-based health care database study in Taiwan included a total of 474 410 subjects. Patients with a new diagnosis of T2DM were enrolled if they received metformin monotherapy between years 1999 and 2010. A 4:1 propensity score-matched cohort of patients with a new diagnosis of T2DM who did not take oral hypoglycemic agents or insulin during follow-up was also enrolled. During a mean 5.8 years of follow-up, the incidence of major adverse cardiovascular events was 1.072% (1072 per 100,000 person-years) in the metformin monotherapy group versus 1.165% in the lifestyle modification group (P < .001). After adjusting for confounders, metformin independently protected the DM patients from major cardiovascular events (hazard ratio: 0.83, P < .001). The metformin group also had an improved cardiovascular event-free survival profile from year 1 to year 12 (P < .001)).
A Cochrane review [withdrawn from publication] included 29 studies with with 37 arms (5259 participants), comparing metformin (37 arms and 2007 participants) with sulphonylureas (13 and 1167), placebo (12 and 702), diet (three and 493), thiazolidinediones (three and 132), insulin (two and 439), meglitinides (two and 208), and glucosidase inhibitors (two and 111). Nine studies reported data on primary outcomes.
Obese patients allocated to intensive blood glucose control with metformin showed a greater benefit than chlorpropamide, glibenclamide, or insulin for any diabetes-related outcomes (P = 0.009), and for all-cause mortality (P = 0.03). Obese participants assigned to intensive blood glucose control with metformin showed a greater benefit than overweight patients on conventional treatment for any diabetes-related outcomes (P = 0.004), diabetes-related death (P = 0.03), all-cause mortality (P = 0.01), and myocardial infarction (P = 0.02). Patients assigned to metformin monotherapy showed a significant benefit for glycaemia control, weight, dyslipidaemia, and diastolic blood pressure. Metformin presents a strong benefit for HbA1c when compared with placebo and diet; and a moderated benefit for: glycaemia control, LDL cholesterol, and BMI or weight when compared with sulphonylureas.
Authors' conclusion: Metformin may be the first therapeutic option in the diabetes mellitus type 2 with overweight or obesity, as it may prevent some vascular complications, and mortality. Sulphonylureas, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, insulin, and diet fail to show more benefit for glycaemia control, body weight, or lipids, than metformin.
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