Takeshi Osonoi, Yutaka Seino, Tomoyuki Nishida, Nobuyuki Abe, Yasuo Terauchi, Daisuke Yabe, Jeppe Zacho, Shizuka Kaneko
Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue in development for type 2 diabetes (T2D). This trial assessed the safety and efficacy of monotherapy with once-weekly subcutaneous (s.c.) semaglutide versus sitagliptin in Japanese subjects with T2D.
Materials and methods
In this phase 3a randomized, open-label, parallel-group, active-controlled, multicentre trial, adult Japanese subjects with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed-out in run-in period) received once-weekly s.c. semaglutide (0.5 or 1.0 mg) or once-daily oral sitagliptin 100 mg. The primary endpoint was number of treatment-emergent adverse events (TEAEs) after 30 weeks.
Overall, 308 subjects were randomized and exposed to treatment, with similar baseline characteristics across groups. In total, 2.9% of subjects in both the semaglutide 0.5 mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0 mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0 mg groups were due to adverse events. More TEAEs were reported in semaglutide- versus sitagliptin-treated subjects (74.8%, 71.6% and 66.0% in the semaglutide 0.5, 1.0 mg and sitagliptin groups, respectively). Adverse events were mainly mild to moderate. Gastrointestinal adverse events, most frequently reported with semaglutide, diminished in frequency over time. Mean HbA1c (baseline 8.1%) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0 mg, respectively, versus 0.7% with sitagliptin (estimated treatment difference versus sitagliptin [ETD] –1.13% [95% confidence interval –1.32; –0.94] and –1.44% [–1.63; –1.24], both p<0.0001). Body weight (baseline 69.3 kg) was reduced by 2.2 and 3.9 kg with semaglutide 0.5 and 1.0 mg, respectively (ETD –2.22 kg [–3.02; –1.42] and –3.88 kg [–4.70; –3.07]; both p<0.0001).
In Japanese subjects with T2D, more TEAEs were reported with semaglutide versus sitagliptin; however, the semaglutide safety profile was similar to that of other GLP-1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight versus sitagliptin.