SUSTAIN 4: weekly semaglutide a good option after metformin failure
medwireNews: The SUSTAIN 4 findings show that a weekly semaglutide injection offers better metabolic and weight control than insulin in patients with diabetes that is poorly controlled on metformin.
The trial participants took these medications in addition to metformin, together with sulfonylurea if they were taking it at enrollment.
During 30 weeks of treatment, glycated hemoglobin (HbA1c) levels decreased by an absolute 1.21% in 362 patients randomly assigned to take weekly semaglutide 0.5 mg and by 1.64% in the 360 taking semaglutide 1.0 mg, compared with 0.83% in 360 patients assigned to take insulin glargine.
This met the trial’s noninferiority endpoint and was also statistically significant for treatment superiority, J Hans DeVries (Academic Medical Center, Amsterdam, the Netherlands) and co-researchers report in The Lancet Diabetes & Endocrinology.
However, they note that average pre-breakfast fasting self-measured plasma glucose at week 30 in patients taking insulin glargine was 7.1 mmol/L, contrary to the target of 4.0–5.5 mmol/L, suggesting “that a more rigorous titration could have been enforced” and “reflecting a potential limitation of titration often seen in clinical practice.”
As newer drugs, and drug combinations, are developed, we need to choose appropriate therapy in a patient-centered manner.
Significantly more patients taking semaglutide achieved an HbA1c below 7.0%, at rates of 57% and 73% for the 0.5 and 1.0 mg doses, respectively, compared with 38% of the insulin group. And more achieved this without experiencing severe or blood glucose-confirmed hypoglycemia and without weight gain, at a corresponding 47% and 64% versus 16%.
Patients in both semaglutide groups lost weight, on average, whereas the insulin-treated group had an overall weight gain. A total of 37% and 51% of patients taking the 0.5 and 1.0 mg doses, respectively, lost at least 5% of their starting bodyweight, compared with just 5% of the insulin group.
Furthermore, patients taking semaglutide had numerically fewer hypoglycemic episodes than those taking insulin (4–6 vs 11%), which the researchers say is “expected for a therapy with a glucose-dependent mechanism of action.” They note that most episodes occurred in patients who were also taking sulfonylurea.
The safety profile of semaglutide was in line with that reported for other glucagon-like peptide-1 analogs. More patients discontinued semaglutide than insulin because of adverse events (6–8 vs 1%), mostly due to gastrointestinal events.
“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 glycaemic control on metformin with or without a sulfonylurea,” the researchers conclude.
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