A Phase 2, Randomized, Dose-Finding Study of the Novel Once-Weekly Human GLP-1 Analog, Semaglutide, Compared With Placebo and Open-Label Liraglutide in Patients With Type 2 Diabetes

Sep 12, 2015Diabetes care

Finding the Right Dose of Once-Weekly Semaglutide Compared to Placebo and Daily Liraglutide in People with Type 2 Diabetes

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Abstract

Semaglutide reduced HbA1c levels by up to 1.7% and body weight by up to 4.8 kg over 12 weeks.

A decrease in HbA1c from a baseline of 8.1% was observed in patients receiving semaglutide.
Up to 81% of patients treated with semaglutide achieved an HbA1c level of less than 7%.
Reductions in HbA1c and weight with semaglutide 1.6 mg were greater than those with liraglutide 1.2 and 1.8 mg.
The frequency of adverse events increased with higher doses of semaglutide, particularly gastrointestinal issues.
Most adverse events were mild to moderate and improved with dose escalation.
No major hypoglycemia events occurred, and injection site reactions were infrequent.

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OBJECTIVE: To investigate the dose-response relationship of semaglutide versus placebo and open-label liraglutide in terms of glycemic control in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS: This was a 12-week, randomized, double-blind phase 2 trial. Patients (n = 415) were randomized to receive a subcutaneous injection of semaglutide once weekly without dose escalation (0.1-0.8 mg) or with dose escalation (E) (0.4 mg steps to 0.8 or 1.6 mg E over 1-2 weeks), open-label liraglutide once daily (1.2 or 1.8 mg), or placebo. The primary end point was change in HbA1c level from baseline. Secondary end points included change in body weight, safety, and tolerability.

RESULTS: Semaglutide dose-dependently reduced the level of HbA1c from baseline (8.1 ± 0.8%) to week 12 by up to -1.7%, and body weight by up to -4.8 kg (1.6 mg E, P < 0.001 vs. placebo). Up to 81% of patients achieved an HbA1c level of <7%. HbA1c level and weight reductions with semaglutide 1.6 mg E were greater than those with liraglutide 1.2 and 1.8 mg (based on unadjusted CIs), but adverse events (AEs) and withdrawals occurred more frequently. The incidence of nausea, vomiting, and withdrawal due to gastrointestinal AEs increased with the semaglutide dose; most events were mild to moderate, transient, and ameliorated by dose escalation. There were no major episodes of hypoglycemia and few cases of injection site reactions.

CONCLUSIONS: After 12 weeks, semaglutide dose-dependently reduced HbA1c level and weight in patients with type 2 diabetes. No unexpected safety or tolerability concerns were identified; gastrointestinal AEs typical of glucagon-like peptide 1 receptor agonists were mitigated by dose escalation. On this basis, weekly semaglutide doses of 0.5 and 1.0 mg with a 4-week dose escalation were selected for phase 3.

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A Phase 2, Randomized, Dose-Finding Study of the Novel Once-Weekly Human GLP-1 Analog, Semaglutide, Compared With Placebo and Open-Label Liraglutide in Patients With Type 2 Diabetes

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