No significant differences were found in the associations among the 9 available classes of glucose-lowering drugs and the risk of cardiovascular or all-cause mortality, according to a meta-analysis published in JAMA.

The study also found that metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug class.

Suetonia C. Palmer, PhD, Department of Medicine, University of Otago Christchurch, New Zealand, and colleagues conducted a meta-analysis of 301 randomized clinical trials that included 1,417,367 patient-months to determine the relative efficacy and safety associated with a variety of glucose-lowering drugs.

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Of the included studies, 177 trials (56,598 patients) focused on drugs given as monotherapy, 109 trials (53,030 patients) focused on dual therapy (drugs added to metformin), and 29 trials (10,598 patients) focused on triple therapy (drugs added to metformin and sulfonylurea). All trials were conducted during the course of 24 weeks or longer.

The researchers found no significant difference in associations between any drug class as monotherapy, dual therapy, or triple therapy. When compared with metformin, sulfonylurea, thiazolidinedione, and α-glucosidase inhibitor monotherapies were associated with higher HbA1C levels; sulfonylurea and basal insulin were associated with the greatest odds of hypoglycemia.

“Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality,” stated Dr Palmer. “Metformin was associated with lower or no significant difference in HbA1c levels compared with any other drug classes.”

Dr Palmer and colleagues also noted that all drugs were estimated to be effective when added to metformin.

“These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations,” Dr Palmer concluded.


  1. Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes. A meta-analysis. JAMA. 2016;316(3):313-214; doi: 10.1001/jama.2016.9400