Semaglutide With SGLT2s Reduces A1C, Weight for Those Not Meeting Diabetes Goals

Adding the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide to a sodium glucose co-transporter 2 (SGLT2) inhibitor allowed most patients with type 2 diabetes (T2D) who were not meeting glycemic targets to achieve them while losing weight, according to a study that appeared Friday in Lancet Diabetes and Endocrinology.¹

The study, SUSTAIN 9, is the latest round of results for the once-weekly GLP-1 receptor agonist sold by Novo Nordisk as Ozempic; an oral form of the drug is also being studied. Results show that if T2D patients hit a plateau while taking SGLT2 inhibitors without reaching a glycated hemoglobin (A1C) of 7%, the target recommended by the American Diabetes Association, adding the injectable semaglutide can help most of them get to that goal. The treatment also helped the majority reduce weight and waist circumference, a measurement that has gained increased attention as a barometer for cardiovascular risk.²

The potential of using the GLP-1 receptor agonist and SGLT2 inhibitor in combination has existed since these classes were approved, said Todd Hobbs, MD, diabetes chief medical officer, North America, for Novo Nordisk, in an interview with The American Journal of Managed Care®. “The 2 agents use very different mechanisms of action; they both have very positive action on glucose as well as weight,” he said. The results showed that among a group of patients who started with an A1C between 7% and 10%, semaglutide allowed 3 of every 4 patients to achieve the recommended ADA target, Hobbs said.

“It was very well tolerated and safe,” he said. “The patients did very well.”

In the study, 302 patients who were already taking an SGLT2 inhibitor for at least 90 days were randomly assigned to receive 1.0 mg of semaglutide or placebo (1 patient was assigned to the treatment arm, but not treated for unknown reasons). The study used a dose escalation schedule of 0.25 mg for 4 weeks, followed by 0.5 mg for 4 weeks, then 30 weeks at the full dose.

Of the group, 294 (97.4%) completed the trial and 264 (88.4%) completed treatment. Most the patients were also taking metformin (216 patients, 71.5%) and a small number were also taking a sulfonylurea (39 patients, 12.9%). Results showed:

• Patients taking semaglutide had greater reductions in A1C; the group saw a difference of -1.42% (95% CI, -1.61 to -1.24).
• The semaglutide group also had greater average weight loss; -3.81 kg (-4.70 to -2.93) compared to those taking placebo. More patients in the treatment arm achieved mean weight reductions of 5% or 10% at week 30.
• The semaglutide arm had a greater average reduction in waist circumference, -2.83 cm (-4.08 cm to -1.59 cm).
• For adverse events (AEs), 356 were reported among 104 patients in the semaglutide group, and 247 events were reported by 91 in the placebo group. The study reported that gastrointestinal AEs were the most common reported events (56 in the treatment arm; 20 in the placebo group). Gastrointestinal events were frequently reported in the GLP-1 class during the dose escalation period.
• Severe hypoglycemic events were confirmed in 4 patients in the semaglutide group; Hobbs said these were more common among patients also taking sulfonylureas.
• Sixteen patients stopped treatment, including 13 in the semaglutide group.

The study used agents from 3 SGLT2 inhibitors approved in the United States—canagliflozin, dapagliflozin, and empagliflozin—as well as an agent approved in Japan. Hobbs said the study did not report results by agent.

Last fall, the American College of Cardiology issued a consensus pathway statement endorsing the use of SGLT2 inhibitors and GLP-1 receptor agonists for patients with T2D and cardiovascular risk; ADA also called for GLP-1 receptor agonists to be the preferred injectable agent before insulin for T2D patients. Hobbs said the fact that these guideline embrace the use of these newer agents should address the clinical inertia that has been seen in primary care practice, where most patients with T2D receive care.

“Endocrinologists have really embraced the use of the guidelines,” Hobbs said, but uptake of GLP-1 receptor agonists in primary care is still low, despite their ability to help patients lose weight. Hobbs noted that patient-reported outcomes in the study findings favored semaglutide, (including health-related quality-of-life scores).

“We will be talking about the use of the guidelines—the use of these agents that will have cardiovascular benefits will overcome some of that inertia—and that’s where this study come in,” he said.

References

1. Zinman B, Bhasekar V, Busch R, et al. Semaglutide once weekly as add-on to SGLT2 inhibitor therapy in type 2 diabetes (SUSTAIN 9): a randomised, placebo-controlled trial [published online March 1, 2019]. Lancet Diabetes Endocrinol. 2019; http://dx.doi.org/10.1016/.
2. Figueiro TH, Arins GCB, Santos CESD, et al. Association of objectively measured sedentary behavior and physical activity with cardiometabolic risk markers in older adults. PLoS One. 2019; 14(1):e0210861. doi: 10.1371/journal.pone.0210861.