All classes of antidiabetic drugs can improve glucose control in dual therapy with sulfonylurea, but sodium glucose co-transporter-2 (SGLT2) inhibitors showed superior outcomes for weight loss and did not increase risk for hypoglycemia, according to findings published in PLoS One.

Metformin is the preferred therapeutic option for type 2 diabetes (T2D), but its use may be contraindicated in or not tolerated by some patients. In these cases, other hypoglycemic agents may be used as first-line therapy. Because of favorable safety and efficacy profiles, sulfonylureas are a common choice despite the potential to increase the incidence of hypoglycemic events and weight gain. 

Nonetheless, as beta-cell function declines over the course of T2D, most patients who initially use sulfonylurea monotherapy will later require combination therapies to maintain glycemic control. A systematic review and network meta-analysis was conducted to investigate the efficacy and safety of dual therapies combining sulfonylurea with antidiabetic drugs for T2D, with the primary end point of analyzing risk for hypoglycemia.

A total of 24 trials with 10,032 patients were included in the analysis. Overall results showed that all treatment regimens were associated with a significantly higher risk for hypoglycemia compared with placebo with the exceptions of sulfonylurea plus SGLT2 inhibitors (odds ratio, 1.35; 95% CI, 0.81-2.25) and alpha-glucosidase inhibitor (odds ratio, 1.16; 95% CI, 0.55-2.44). Sulfonylurea combined with glucagon-like peptide-1 receptor agonist was associated with the most significant increased risk for hypoglycemia, but all sulfonylurea-based regimens reduced glycated hemoglobin and fasting plasma glucose levels. Of note, only regimens containing SGLT2 inhibitors (mean difference, -1.00 kg; 95% CI, -1.73 to -0.27) and glucagon-like peptide-1 receptor agonist (mean difference, -0.56 kg; 95% CI, -1.10 to -0.02) led to weight loss.

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“[SGLT2 inhibitors] exhibited superior effects in terms of weight loss and did not increase the risk [for] hypoglycemia, suggesting that it might be the best option…when selecting antidiabetic drugs for administration together with [sulfonylurea],” concluded the researchers.


Qian D, Zhang T, Tan X, et al. Comparison of antidiabetic drugs added to sulfonylurea monotherapy in patients with type 2 diabetes mellitus: a network meta-analysis. PLoS One. 2018;13(8):e0202563.