Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-analysis


Apostolos Tsapas 1, Ioannis Avgerinos 2, Thomas Karagiannis 2, Konstantinos Malandris 2, Apostolos Manolopoulos 2, Panagiotis Andreadis 3, Aris Liakos 2, David R Matthews 4, Eleni Bekiari

Main idea: In diabetic patients at low cardiovascular risk, no treatment differs from placebo for vascular outcomes. In patients at increased cardiovascular risk receiving metformin-based background therapy, specific GLP-1 RAs and SGLT-2 inhibitors have a favorable effect on certain cardiovascular outcomes.


Background: Several pharmacologic options for type 2 diabetes are available.

Purpose: To compare benefits and harms of glucose-lowering drugs in adults with type 2 diabetes.

Data synthesis: 453 trials assessing 21 antidiabetic interventions from 9 drug classes were included. Interventions included monotherapies (134 trials), add-on to metformin-based therapies (296 trials) There were no differences between treatments in drug-naive patients at low cardiovascular risk. Insulin regimens and specific glucagon-like peptide-1 receptor agonists (GLP-1 RAs) produced the greatest reductions in hemoglobin A1c level. In patients at high cardiovascular risk, there were no clinically meaningful differences.

Limitation: Inconsistent definitions of cardiovascular risk and low-level confidence in some estimates for patients at low cardiovascular risk.


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