medwireNews: Patients with type 2 diabetes who are treated with semaglutide experience greater improvements in glycemic control than those given liraglutide, but at the cost of a higher risk for gastrointestinal (GI) adverse events (AEs), researchers report.
In their 26-week trial, Thomas Pieber (Medical University of Graz, Austria) and co-investigators randomly assigned 705 patients with glycated hemoglobin (HbA1c) levels of 7–10% to receive once daily semaglutide at doses of 0.05, 0.1, 0.2, or 0.3 mg, volume-matched equipotent liraglutide doses of 0.3, 0.6, 1.2, or 1.8 mg, or placebo. The researchers note that semaglutide doses equated to 0.35–2.1 mg/week, a wider range than the 0.5 and 1.0 mg weekly doses tested in the SUSTAIN trials.
At baseline, participants were undergoing diet and exercise treatment, with or without metformin. They had an average HbA1c level of 8.1% and an average BMI of 32.8 kg/m2.
Patients in the semaglutide and liraglutide groups experienced a dose-dependent reduction in HbA1c levels from baseline to week 26, ranging from a decrease of 1.1% to 1.9% for semaglutide and from 0.5% to 1.3% for liraglutide. Average HbA1c levels decreased by 0.02% for placebo-treated patients.
The estimated decrease in HbA1c levels was significantly greater for all semaglutide doses versus placebo, and for each dose of semaglutide compared with the equivalent dose of liraglutide, report the researchers in Diabetes Care.
Moreover, semaglutide-treated patients experienced a dose-dependent decrease in bodyweight, with average reductions ranging from 2.8 to 8.2 kg, compared with 1.5 to 3.7 kg for those in the liraglutide groups and 1.2 kg for patients given placebo. Reductions in bodyweight were significantly greater between each dose of semaglutide versus liraglutide except for the lowest dose.
GI disorders were the most commonly reported AEs in the semaglutide and liraglutide arms, affecting 32.8–54.0% and 21.9–41.5% of patients, respectively, and 22.5% of those in the placebo arm. A corresponding 6.3–7.9%, 3.1–7.8%, and 10.9% of patients experienced AEs leading to treatment discontinuation.
Pieber and colleagues say that the potency of semaglutide was 28 times higher than that of liraglutide for HbA1c reduction and 30 times higher for weight loss, based on the ratio between the equipotent doses. However, the equivalent dose ratio was 12.8 for GI AEs and 7.4 for AEs leading to treatment discontinuation, suggesting that “greater reductions in HbA1c and body weight might be achieved with semaglutide without an increase in the risk of GI AEs compared with liraglutide,” they add.
Nevertheless, because a greater proportion of patients in the semaglutide than the liraglutide group discontinued treatment due to GI AEs (1.6–4.7 vs 1.6–3.1%), they say that “the greater efficacy of semaglutide was not sufficient to maintain adherence to treatment.”
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- SUSTAIN 1: ‘high degree’ of glycemic control with semaglutide in type 2 diabetes
- SUSTAIN 2 shows better glycemic control with semaglutide than sitagliptin
- Semaglutide at least equivalent to exenatide on weekly schedule
- SUSTAIN 4: weekly semaglutide a good option after metformin failure
- SUSTAIN 7 published: Semaglutide superior to dulaglutide