Semaglutide promising add-on to metformin in type 2 diabetes

By Reuters Staff

NEW YORK (Reuters Health) - In patients with type 2 diabetes poorly controlled on metformin (with or without sulfonylureas), adding a once-weekly injection of semaglutide provided better metabolic and weight control than adding a once-daily injection of insulin glargine in the SUSTAIN 4 study.

“Combined with its cardiovascular risk reduction effect noted in SUSTAIN 6, semaglutide seems to be an effective once-weekly therapeutic option for patients with type 2 diabetes who are unable to achieve glycemic control on metformin with or without a sulfonylurea,” the researchers conclude.

SUSTAIN 4 was a randomized, open-label, non-inferiority, parallel-group phase 3a trial conducted at 196 sites in 14 countries. The trial enrolled insulin-naive adults with type 2 diabetes who had inadequate glycemic control with metformin either alone or in combination with a sulfonylurea.

Participants were randomly allocated to add either subcutaneous once-weekly semaglutide (0.5 mg or 1.0 mg) or once-daily insulin glargine (starting dose 10 IU per day, titrated weekly to a pre-breakfast plasma glucose target of 4.0 to 5.5 mmol/L). All patients continued their previous background metformin and sulfonylurea treatment.

Over 30 weeks of treatment, from a mean baseline hemoglobin (Hb)A1c of 8.17%, HbA1c levels decreased by an absolute 1.21% in 362 patients on semaglutide 0.5 mg and by 1.64% in the 360 on semaglutide 1.0 mg, compared with 0.83% in 360 on insulin glargine.

More people in the semaglutide groups achieved HbA1c <7% or 6.5% or lower, than in the insulin glargine group (p<0.0001 for all), Dr. J. Hans DeVries, of the Academic Medical Center in Amsterdam and colleagues report online March 23 in The Lancet Diabetes & Endocrinology.

Treatment with semaglutide also led to substantial weight loss (-3.5 to -5.2 kg vs. baseline), with more participants on either dose of semaglutide achieving a clinically significant weight reduction of 5% or more than those on insulin glargine.

“We identified no new safety issues for semaglutide,” the researchers say, adding, “The safety profile of gradually titrated semaglutide appears to be similar to currently available GLP-1 receptor agonists, with adverse events consisting mainly of gastrointestinal events such as nausea and diarrhea, with a lower risk of hypoglycemia than insulin glargine.”

“Our trial population was heterogeneous, encompassing a broad range in terms of age, duration of diabetes, and level of HbA1c at baseline. The population was also ethnically diverse compared with other phase 3a clinical trial programs in patients with type 2 diabetes,” they note.

Limitations of the study include the open-label design and short duration, which don't allow any conclusions to be drawn regarding the long-term efficacy and tolerability of semaglutide compared with insulin glargine, the researchers say. They also note that insulin glargine did not achieve titration targets.

Dr. DeVries and colleagues conclude, “The combination of glycemic control and bodyweight reduction with a low potential for hypoglycemia, delivered with a once-weekly injection of semaglutide, is a promising finding given that a high proportion of patients with type 2 diabetes are overweight or obese and many other treatments either do not affect weight or are associated with weight gain accompanied by hypoglycemia or the need to be injected daily.”

The study was funded by Novo Nordisk. Several authors have disclosed relationships with the company, including employment.

SOURCE: http://bit.ly/2nfYaeU

Lancet Diab Endocrinol 2017.

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