From the Journals

Semaglutide plus SGLT2 inhibitors improves glycemic control in type 2 diabetes



Adding once-weekly treatment with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide helped most patients with type 2 diabetes already being treated with sodium-glucose cotransporter-2 (SGLT2) inhibitors meet their glycemic targets and lose weight, researchers reported.

“Combining the distinct modes of action of these two drug classes has beneficial effects on glucose and weight outcomes,” wrote Bernard Zinman, MD, of Mount Sinai Hospital, Toronto, and his coauthors. Their report is in Lancet Diabetes and Endocrinology.

In the international, double-blind, phase 3 SUSTAIN 9 trial, 302 patients with type 2 diabetes whose hemoglobin A1c (HbA1c) levels were 7.0% to 10.0% (53 to 86 mmol/mol) despite at least 90 days of SGLT2-inhibitor therapy (alone or with metformin or sulfonylurea) were randomly assigned to add either once-weekly semaglutide (1-mg injection) or placebo to their regimen.

A total of 294 patients completed the trial. After 30 weeks, those who had received adjunctive semaglutide had significantly greater reductions in their HbA1c levels (estimated treatment difference, –1.42%; P less than .0001). They also lost about 3.81 kg more bodyweight than did patients in the placebo group and they had significantly greater reductions in mean body mass index, waist circumference, fasting and self-measured blood glucose, systolic blood pressure, pulse rate, total cholesterol, and low-density lipoprotein and triglyceride levels.

The most commonly reported adverse effects of semaglutide were nausea, diarrhea, vomiting, and constipation, which were usually mild in severity. Severe or blood-glucose–confirmed hypoglycemia occurred in 2.7% patients on semaglutide and none on placebo. However, most patients who received semaglutide achieved an HbA1c of 7.0% (53 mmol/mol) or less without weight gain or severe or blood-glucose–confirmed hypoglycemia (P less than .0001 vs. placebo).

Novo Nordisk funded the study. Three of the authors were employees of Novo Nordisk at the time of the study, and the remaining authors reported that they and/or their institutions had received funding from the company.

SOURCE: Zinman B et al. Lancet Diabetes Endocrinol. 2019 Mar 1. doi: 10.1016/S2213-8587(19)30066-X.

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