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Novo Nordisk's Semaglutide Beats Dulaglutide on A1C, Weight Loss in Head-to-Head Trial

Mary Caffrey
A cardiovascular outcomes trial has already shown a reduction in cardiovascular events, but not deaths.
Novo Nordisk’s once-weekly semaglutide has outperformed another weekly therapy, dulaglutide, in controlling blood glucose and helping patients with type 2 diabetes (T2D) lose weight. The drug also overcame concerns about retinopathy that appeared in an earlier trial. The company reported results from the SUSTAIN 7 trial in a statement late Wednesday.

The 40-week trial compared safety and efficacy of the smaller and larger doses of the 2 drugs head-to-head. The semaglutide doses are 0.5 mg and 1.0 mg and the dulaglutide doses are 0.75 mg and 1.5 mg; all doses were added to metformin. Dulaglutide, sold as Trulicity by Eli Lilly, was approved in September 2014.

Trial results showed:

  • Patients with a mean glycated hemoglobin (A1C) of 8.2% who took the 0.5 dose of semaglutide achieved an A1C reduction of 1.5%, compared with a 1.1% reduction for those who took the 0.75 mg of dulaglutide. 
  • Also starting with a mean A1C of 8.2%, patients who took the 1.0 mg dose of semaglutide saw an A1C reduction of 1.8%, compared with a reduction of 1.4% for those taking the 1.5 mg dose of dulaglutide.
  • From a mean baseline weight of 95 mg and body mass index of 33.5 mg/m2, those treated with 0.5 mg of semaglutide lost 4.6 kg, compared with 2.3 kg with 0.75 of dulaglutide. Those taking 1.0 mg of semaglutide lost 6.5 kg, compared with 3.0 kg with 1.5 mg dulaglutide
  • More patients taking semaglutide reached goals of the American Diabetes Association of 7% A1C: 69% taking 0.5 mg semaglutide compared with 52% taking 0.75 dulaglutide; and 79% taking 1.0 mg semaglutide compared with 1.5 mg dulaglutide. Fewer patients achieved the stricter target of 6.5% set by the American Association of Clinical Endocrinologists, but a higher share were taking semaglutide.

Among the patients, 44% of those taking 0.5 mg semaglutide and 63% taking 1.0 mg semaglutide achieved 5% weight loss, compared with 23% and 30% for the smaller and larger doses of dulaglutide. Guidelines for CDC’s Diabetes Prevention Program call a 5% weight loss or greater “transformational,” which means significant health benefits occur.

Semaglutide, the next entrant in the powerful class of glucagon-like-1 (GLP-1) receptor agonists, is under review by FDA and European regulators. Novo Nordisk has already reported results from a cardiovascular outcomes trial that show the drug cut cardiovascular events by 26%, although not deaths. That trial showed a slight uptick in retinopathy, but the new trial did not show any disparity in these events with dulaglutide.

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