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Liraglutide monotherapy, administered once daily for 24 weeks in Japanese subjects with T2DM, was well tolerated. Compared with glibenclamide monotherapy, liraglutide achieved superior glycaemic control and weight outcome, and a significantly lower incidence of hypoglycaemia. Future studies, comprising a greater proportion of true therapy-naïve Japanese patients, will be beneficial in order to establish the true add-on efficacy of liraglutide monotherapy in patients with T2DM.

AimsTo assess the safety and efficacy of monotherapy with once‐weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D).MethodsIn this phase IIIa randomized, open‐label, parallel‐group, active‐controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the 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.ResultsOverall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants 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 attributable to adverse events (AEs). More TEAEs were reported in semaglutide‐ vs sitagliptin‐treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5 mg, semaglutide 1.0 mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0 mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin −1.13%, 95% confidence interval [CI] −1.32; −0.94, and −1.44%, 95% CI −1.63; −1.24; both P < .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, 95% CI −3.02; −1.42 and −3.88 kg, 95% CI −4.70; −3.07; both P < .0001).ConclusionsIn Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon‐like peptide‐1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin.

AimTo evaluate the safety and efficacy of once‐weekly subcutaneous semaglutide as monotherapy or combined with an oral antidiabetic drug (OAD) vs an additional OAD added to background therapy in Japanese people with type 2 diabetes (T2D) inadequately controlled on diet/exercise or OAD monotherapy.MethodsIn this phase III, open‐label trial, adults with T2D were randomized 2:2:1 to semaglutide 0.5 mg or 1.0 mg, or one additional OAD (a dipeptidyl peptidase‐4 inhibitor, biguanide, sulphonylurea, glinide, α‐glucosidase inhibitor or thiazolidinedione) with a different mode of action from that of background therapy. The primary endpoint was number of adverse events (AEs) after 56 weeks.ResultsBaseline characteristics were balanced between treatment arms (601 randomized). More AEs were reported in the semaglutide 0.5 mg (86.2%) and 1.0 mg (88.0%) groups than in the additional OAD group (71.7%). These were typically mild/moderate. Gastrointestinal AEs were most frequent with semaglutide, which diminished over time. The mean glycated haemoglobin (HbA1c) concentration (baseline 8.1%) was significantly reduced with semaglutide 0.5 mg and 1.0 mg vs additional OAD (1.7% and 2.0% vs 0.7%, respectively; estimated treatment difference [ETD] vs additional OAD −1.08% and −1.37%, both P < .0001). Body weight (baseline 71.5 kg) was reduced by 1.4 kg and 3.2 kg with semaglutide 0.5 mg and 1.0 mg, vs a 0.4‐kg increase with additional OAD (ETD −1.84 kg and −3.59 kg; both P < .0001). For semaglutide‐treated participants, >80% achieved an HbA1c concentration <7.0% (Japanese Diabetes Society target).ConclusionsSemaglutide was well tolerated, with no new safety issues identified. Semaglutide treatment significantly reduced HbA1c and body weight vs additional OAD treatment in Japanese people with T2D.

Aims To investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) compared with its individual components in Japanese people with type 2 diabetes (T2D) uncontrolled on an oral antidiabetic drug (OAD). Materials and methods This 52‐week, open‐label, multicentre, treat‐to‐target trial randomized participants (n = 819) 1:1:1 to IDegLira, liraglutide 1.8 mg or degludec, as add‐on to their pre‐trial OAD. The maximum IDegLira dose was 50 dose steps (50 U degludec/1.8 mg liraglutide), there was no maximum dose for degludec, and both were titrated based on individual blood glucose measurements. Results After 52 weeks, glycated haemoglobin (HbA1c) decreased by 26 mmol/mol with IDegLira vs 20 mmol/mol with degludec and liraglutide: estimated treatment differences were −6.91 mmol/mol (95% confidence interval [CI] –8.18; −5.64) and −5.30 mmol/mol (95% CI −6.58; −4.03), confirming non‐inferiority of IDegLira to degludec and superiority of IDegLira to liraglutide (P < .0001 for both [primary endpoint]). Mean body weight changes were 2.9 kg, 4.1 kg and −1.0 kg with IDegLira, degludec and liraglutide, respectively, showing superiority of IDegLira versus degludec (P = .0001), but a significant difference in favour of liraglutide (P < .0001). Rates of severe or blood glucose‐confirmed hypoglycaemia for IDegLira were lower versus degludec (rate ratio 0.48 [95% CI 0.35; 0.68]; P < .0001), but higher versus liraglutide (rate ratio 37.58 [95% CI 19.80; 71.31]; P < .0001). Mean daily total insulin dose was lower with IDegLira (27.7 U) versus degludec (34.8 U; P < .0001). Overall adverse event (AE) rates were similar. In total, 34.9%, 22.9% and 41.8% of IDegLira‐, degludec‐ and liraglutide‐treated participants experienced gastrointestinal AEs. Conclusion IDegLira was superior to degludec and liraglutide in terms of HbA1c reduction and superior to degludec in terms of body weight change and rates of hypoglycaemia in Japanese people with T2D.