Cardiovascular, All-Cause Mortality Similar for Glucose-Lowering Drugs in Type 2 Diabetes

Share this content:
Metformin was associated with reductions in bodyweight relative to sulfonylurea or thiazolidinedione.
Metformin was associated with reductions in bodyweight relative to sulfonylurea or thiazolidinedione.

For the 9 available classes of glucose-lowering drugs, the risk for cardiovascular (CV) or all-cause mortality was comparable among adults with type 2 diabetes, according to recent data published in the Journal of the American Medical Association.

Researchers conducted a meta-analysis that included a total of 301 clinical trials (1,417,367 patient-months). Of these, 177 trials included glucose-lowering drugs given as monotherapy, 109 trials included drugs added to metformin (dual therapy), and 29 trials included drugs added to metformin and a sulfonylurea (triple therapy).

Among the 11,094 patients included in the analysis, there were no significant differences in the associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of CV or all-cause mortality.

Compared with metformin, sulfonylurea (standardized mean difference [SMD]: 0.18; 95% CI, 0.01-0.34), thiazolidinedione (SMD: 0.16; 95% CI, 0.00-0.31), dipeptidyl peptidase-4 (DPP-4) inhibitor (SMD: 0.33; 95% CI, 0.13-0.52), and alpha-glucosidase inhibitor (SMD, 0.35; 95% CI, 0.12-0.58) monotherapy was associated with higher HbA1c levels.

The researchers also found the highest odds for hypoglycemia were associated with sulfonylurea (odds ratio [OR], 3.13; 95% CI, 2.39-4.12; risk difference [RD]: 10%; 95% CI, 7-13) and basal insulin (OR, 17.9; 95% CI, 1.97-162; RD, 10%; 95% CI, 0.08-20).

“Metformin was associated with small reductions in bodyweight relative to sulfonylurea or thiazolidinedione treatment,” the study authors wrote.

“Based on this review, clinicians and patients may prefer to avoid sulfonylureas or basal insulin for patients who wish to minimize hypoglycemia, choose GLP-1 receptor agonists when weight management is a priority, or consider SGLT-2 (sodium glucose cotransporter-2) inhibitors based on their favorable combined safety and efficacy profile.”

Drugs maintained similar HbA1c levels when added to metformin, while SGLT-2 inhibitors were associated with the lowest odds of hypoglycemia (OR, 0.12; 95% CI, 0.08-0.18; RD, –22%; 95%, CI –22 to –18).

In addition, glucagon-like peptide-1 (GLP-1) receptor agonists were associated with the lowest odds of hypoglycemia when added to metformin and sulfonylurea (OR, 0.60; 95% CI, 0.39-0.94; RD, –10%; 95% CI, –18 to –2).

“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,” the researchers concluded.

Disclosures: Several researchers reported receiving research support, speaker's honoraria, and serving as consultants for pharmaceutical companies. 


  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):313-324. doi:10.1001/jama.2016.9400.
You must be a registered member of Endocrinology Advisor to post a comment.

Sign Up for Free e-Newsletters

CME Focus