Article type
Year
Abstract
Background: Metformin is widely used as an antihyperglycaemic agent in type 2 diabetes but more information about efficacy on primary and secondary outcomes when directly compared with the rest of agents used for glycaemic control in type 2 diabetes is needed.
Objectives: To assess the efficacy of metformin monotherapy, compared with placebo, diet, insulin, a glucosidase inhibitors, meglitinides, sulphonylureas, and thiazolidinediones, in improving clinical, and biochemical features of type 2 diabetes by using literature review and meta-analysis.
Methods: Systematic review of randomised controlled trials. Cochrane review manager software (RevMan 4.2; Oxford, UK), for managing and analysing the data. We used meta-regression techniques (Stata; StataCorp LP, Texas, USA), to identify possible sources of heterogeneity. We assess all relevant any-language studies identified in searches of the MEDLINE (1966 to September 2003), EMBASE ( 1974 to September 2003), LILACS (1986 to September 2003), Cochrane Library databases, and reference lists of key articles. Contacting manufacturers, for additional unpublished reports. A citation duplication check search was completed. Two reviewers independently rated study quality on the basis of established criteria. We computed weighted mean differences (WMD) for all data emanating for the same scale. Combining data from different scales was achieved using standardized mean differences (SMD). Intention to treat analysis was included. Dichotomous data were expressed as the number of events, and relative risk. All analyses were completed using a random effects model. We undertook sensitivity analyses based on quality, and design. We undertook subgroup analysis on obesity, blood pressure, LDL cholesterol levels, and fibrinogen. We assess for the presence of publication bias.
Results: 29 trials with 36 arms were identified (metformin 36, sulphonylureas 13, placebo 12, diet 3, thiazolidinediones 3, meglitinides 2, a glucosidase inhibitors 2, and insulin 1). There was no obvious publication or related bias. With the exception of obesity reported in 17 studies, we were unable to complete other planned subgroup analyses because of a paucity of data. No trial reported specific results for participants older than 65 years of age. Intensive metformin showed more benefit than sulphonylureas or insulin for any clinical end point related to diabetes (relative risk 0.78, 95% confidence interval 0.65 to 0.94), and more benefit than conventional intervention (0.74, 0.60 to 0.90). Metformin had more benefit on glycated haemoglobin than placebo (weighted mean difference 1.06% (95% confidence interval -1.38 to -0.73)), diet (-1.44% ( 2.62 to -0.26)), and thiazolidinediones (-0.24% (-0.46 to -0.02)), and more benefit on body mass index than sulphonylureas (standardised mean difference -0.58 (-1.00 to -0.16)).
Conclusion: In the long-term intensive metformin has a significant risk reduction for any clinical end point related to diabetes. More benefit is achieved in overweight patients. There are not long term trials for comparing more recent drugs with metformin for primary outcomes. Placebo, diet, insulin, and the rest of oral agents fail to present more benefit than metformin for secondary outcomes.
Objectives: To assess the efficacy of metformin monotherapy, compared with placebo, diet, insulin, a glucosidase inhibitors, meglitinides, sulphonylureas, and thiazolidinediones, in improving clinical, and biochemical features of type 2 diabetes by using literature review and meta-analysis.
Methods: Systematic review of randomised controlled trials. Cochrane review manager software (RevMan 4.2; Oxford, UK), for managing and analysing the data. We used meta-regression techniques (Stata; StataCorp LP, Texas, USA), to identify possible sources of heterogeneity. We assess all relevant any-language studies identified in searches of the MEDLINE (1966 to September 2003), EMBASE ( 1974 to September 2003), LILACS (1986 to September 2003), Cochrane Library databases, and reference lists of key articles. Contacting manufacturers, for additional unpublished reports. A citation duplication check search was completed. Two reviewers independently rated study quality on the basis of established criteria. We computed weighted mean differences (WMD) for all data emanating for the same scale. Combining data from different scales was achieved using standardized mean differences (SMD). Intention to treat analysis was included. Dichotomous data were expressed as the number of events, and relative risk. All analyses were completed using a random effects model. We undertook sensitivity analyses based on quality, and design. We undertook subgroup analysis on obesity, blood pressure, LDL cholesterol levels, and fibrinogen. We assess for the presence of publication bias.
Results: 29 trials with 36 arms were identified (metformin 36, sulphonylureas 13, placebo 12, diet 3, thiazolidinediones 3, meglitinides 2, a glucosidase inhibitors 2, and insulin 1). There was no obvious publication or related bias. With the exception of obesity reported in 17 studies, we were unable to complete other planned subgroup analyses because of a paucity of data. No trial reported specific results for participants older than 65 years of age. Intensive metformin showed more benefit than sulphonylureas or insulin for any clinical end point related to diabetes (relative risk 0.78, 95% confidence interval 0.65 to 0.94), and more benefit than conventional intervention (0.74, 0.60 to 0.90). Metformin had more benefit on glycated haemoglobin than placebo (weighted mean difference 1.06% (95% confidence interval -1.38 to -0.73)), diet (-1.44% ( 2.62 to -0.26)), and thiazolidinediones (-0.24% (-0.46 to -0.02)), and more benefit on body mass index than sulphonylureas (standardised mean difference -0.58 (-1.00 to -0.16)).
Conclusion: In the long-term intensive metformin has a significant risk reduction for any clinical end point related to diabetes. More benefit is achieved in overweight patients. There are not long term trials for comparing more recent drugs with metformin for primary outcomes. Placebo, diet, insulin, and the rest of oral agents fail to present more benefit than metformin for secondary outcomes.