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Greater HbA1c reduction seen with semaglutide vs. liraglutide
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In patients with type 2 diabetes, once-daily semaglutide was associated with greater decreases in HbA1c vs. liraglutide over 26 weeks, but also a greater incidence of gastrointestinal adverse events, according to study findings published in Diabetes Care.
“In the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) phase 3a global clinical trial program in patients with type 2 diabetes, once-weekly subcutaneous semaglutide 0.5 mg and 1 mg showed superior and clinically meaningful reductions in HbA1c and body weight vs. a wide range of comparators,” Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center at Dallas, and colleagues said in the study background. “The effect of semaglutide on gastric emptying was investigated in a separate trial and showed that although overall gastric emptying was similar to that of placebo, the observed first-hour delay with semaglutide may contribute to a slower entry of glucose into the circulation.”
In a 26-week randomized, double-blind, dose-finding trial conducted across 138 sites in 10 countries, researchers compared semaglutide (Ozempic, Novo Nordisk) with liraglutide (Victoza, Novo Nordisk) and placebo, all administered subcutaneously once a day, in 705 patients with type 2 diabetes and HbA1c between 7% and 10% (mean age, 57 years; 42.6% women; mean HbA1c, 8.1%). Researchers randomly assigned participants to one of 12 treatment arms at a 2:2:1 ratio (semaglutide, liraglutide, placebo) at each of four dosing levels (50 mL, 100 mL, 200 mL and 300 mL) or to a 13th semaglutide treatment group with the same number of participants as in the active intervention arms. This was consistent with the following daily doses: semaglutide 0.05 mg, 0.1 mg, 0.2 mg or 0.3 mg and liraglutide 0.3 mg, 0.6 mg, 1.2 mg and 1.8 mg. The 13th treatment arm represented the exploratory semaglutide flexible escalation arm based on tolerability of gastrointestinal adverse events.
After a 2-week screening interval, patients initiated a regimen of trial medication, taken for 26 weeks, followed by a 7-week follow-up period.
At 26 weeks, researchers observed a dose-dependent estimated mean reduction in HbA1c with semaglutide ranging from –1.1% in the 0.05-mg group to –1.9% in the 0.3-mg group. In the liraglutide-treated patients, mean HbA1c decreases ranged from –0.5% in the 0.3-mg group to –1.3% in the 1.8-mg group (P < .001 for all). The pooled placebo group achieved a mean HbA1c change of –0.02% (P < .0001 vs. semaglutide).
In a dose-response model for semaglutide and liraglutide, researchers found that liraglutide 1.8 mg was equal in potency to semaglutide 0.062 mg.
At week 26, 43% to 73% of patients assigned various doses of semaglutide met the HbA1c target of 6.5% or less, whereas 14% to 42% of participants assigned liraglutide and 6% of those in the pooled placebo group met this goal, according to researchers.
Gastrointestinal disorders were the most common adverse events in both active treatment arms; however, participants assigned semaglutide experienced more adverse events vs. those assigned liraglutide (32.8% to 54% with semaglutide vs. 21.9% to 41.5% with liraglutide). Most gastrointestinal events occurred in the first 12 weeks. There were no between-group differences for rates of serious adverse events. – by Jennifer Byrne
Disclosures: Novo Nordisk funded this study. Lingvay reports she has received research grants, consultant fees and travel or editorial support from AstraZeneca, Boehringer Ingelheim, GI Dynamics, Lilly, Novo Nordisk, Merck, Pfizer and Sanofi. Please see the study for the other authors’ relevant financial disclosures.
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