Lower Hypoglycemia Risk, Greater Weight Loss With SGLT2 Inhibitor, Sulfonylurea in T2D

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SGLT-2i exhibited superior effects in terms of weight loss and did not increase the risk for hypoglycemia in dual therapy with sulfonylurea.

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.