Picking a Glucose-Lowering Drug: Comparison of Clinical Outcomes and Adverse Events

Study Questions:

What is the relative efficacy and safety associated with glucose-lowering drugs including insulin?


The authors of this meta-analysis included randomized clinical trials comparing two individual glucose-lowering drug classes for treatment of type 2 diabetes. Eligible trials included those in which treatment was given for 24 weeks or longer. The association of drug treatment with cardiovascular mortality was the primary endpoint.


Overall, 301 randomized clinical trials involving 118,094 patients were eligible for inclusion in this review. There were no significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality. There were no significant differences between any drug class when added to metformin for odds of all-cause mortality, serious adverse events, myocardial infarction, or stroke, with the exception of lower odds of stroke associated with metformin and dipeptidyl peptidase 4 (DPP-4) inhibitor versus metformin and sulfonylurea (odds ratio, 0.47; 95% confidence interval, 0.23-0.95).


There were not significant differences in the associations between any of nine available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality.


This is a valuable study, albeit limited by disadvantages inherent to meta-analyses, which established that there are no differences in the associations between glucose-lowering drugs alone or in combination with odds of cardiovascular mortality, all-cause mortality, or myocardial infarction. Such findings are important given the overall uncertainty about the association of drug treatment with cardiovascular outcomes. These results also corroborate recommendations to use metformin monotherapy as initial treatment for patients with type 2 diabetes. Nonetheless, and as the authors summarize in their discussion, ‘A central finding in this meta-analysis was that despite more than 300 available clinical trials involving nearly 120,000 adults and 1.4 million patients-months of treatment, there was limited evidence that any glucose-lowering drug stratified by coexisting treatment prolonged life expectance or prevented cardiovascular disease.’

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Heart Failure and Cardiac Biomarkers

Keywords: Diabetes Mellitus, Type 2, Dipeptidyl Peptidase 4, Glucose, Hypoglycemic Agents, Insulin, Metabolic Syndrome X, Metformin, Myocardial Infarction, Primary Prevention, Risk, Stroke

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