Efficacy and Safety of Semaglutide for Type 2 Diabetes by Race and Ethnicity: A Post Hoc Analysis of the SUSTAIN Trials

Aim To evaluate the efficacy and safety of once‐weekly subcutaneous semaglutide, a glucagon‐like peptide‐1 (GLP‐1) analogue, versus once‐daily sitagliptin as add‐on to metformin in patients with type 2 diabetes (T2D) in a multiregional clinical trial. Materials and Methods In the 30‐week, randomized, double‐blind, double‐dummy, active comparator SUSTAIN China trial, 868 adults with T2D inadequately controlled on metformin (HbA1c 7.0%‐10.5%) were randomized to receive once‐weekly semaglutide 0.5 mg (n = 288), semaglutide 1.0 mg (n = 290) or once‐daily sitagliptin 100 mg (n = 290). The primary and confirmatory secondary endpoints were change from baseline to week 30 in HbA1c and body weight, respectively. Results The trial enrolled ~70% (605/868) of the patients in China, and the remaining patients from four other countries, including the Republic of Korea. Both doses of semaglutide were superior to sitagliptin in reducing HbA1c and body weight after 30 weeks of treatment. The odds of achieving target HbA1c of less than 7.0% (53 mmol/mol), weight loss of 5% or higher, or 10% or higher, and the composite endpoint of HbA1c less than 7.0% (53 mmol/mol) without severe or blood glucose‐confirmed symptomatic hypoglycaemia no weight gain, were all significantly higher with both semaglutide doses compared with sitagliptin. The safety profile for semaglutide was consistent with the known class effects of GLP‐1 receptor agonists (RAs). Consistent efficacy and safety findings were seen in the Chinese subpopulation. Conclusions Once‐weekly semaglutide was superior to sitagliptin in improving glycaemic control and reducing body weight in patients with T2D inadequately controlled on metformin. The safety and tolerability profiles were consistent with those of semaglutide and other GLP‐1 RAs. Semaglutide is an effective once‐weekly treatment option for the Chinese population.

Section: Discussionmentioning

confidence: 97%

Efficacy and safety of once‐weekly semaglutide versus once‐daily sitagliptin as add‐on to metformin in patients with type 2 diabetes in SUSTAIN China: A 30‐week, double‐blind, phase 3a, randomized trial

Dong

et al. 2021

“…In our study, the mean HbA1c reduction in the PEX168/200 μg group was 1.34%. Some previous studies of long‐acting GLP‐1 RAs had similar HbA1c reductions: 1.33% with liraglutide monotherapy (0.9 mg) for 26 weeks in Japanese patients, 12 1.48% with dulaglutide monotherapy (1.5 mg) for 26 weeks in East Asian patients, 13 1.53% with once‐weekly exenatide (2.0 mg) for 26 weeks in a diverse patient population (67% Caucasian, 12.4% East Asian), 14 and 2.0% with semaglutide (1.0 mg) for 30 weeks in Asian patients 15 …”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of polyethylene glycol loxenatide monotherapy in type 2 diabetes patients: A multicentre, randomized, double‐blind, placebo‐controlled phase 3a clinical trial

Shi

Yang

Zhang

et al. 2020

Aim To evaluate the efficacy and safety of polyethylene glycol loxenatide (PEX168) monotherapy in type 2 diabetes (T2D) patients in China. Materials and Methods In a multicentred, randomized, double‐blinded, placebo‐controlled phase 3a clinical trial, 361 patients with inadequate glycaemic control (HbA1c 7.0%‐10.5%, fasting plasma glucose <13.9 mmol/L) were randomized (1:1:1) for weekly subcutaneous injections: placebo, PEX168/100 μg or PEX168/200 μg. The 24‐week treatment was followed by a 28‐week extension, during which placebo‐treated patients were randomly assigned to PEX168/100 μg or PEX168/200 μg. The primary efficacy endpoint was the HbA1c change from baseline to week 24. Results The three groups had similar demographics and baseline characteristics. The HbA1c least‐square mean (95% CI) change from baseline to week 24 was greater for PEX168/100 μg (−1.02% [−1.21%, −0.83%]) and PEX168/200 μg (−1.34% [−1.54%, −1.15%]) than for placebo (−0.17% [−0.36%, 0.02%]); (superiority: P < .0001). The proportions of patients with less than 7% HbA1c in the placebo, PEX168/100 μg and PEX168/200 μg groups were 15.7%, 34.7% and 46.6%, respectively. Common gastrointestinal adverse events (AEs) were nausea (5.6%, 10.0% and 0% for PEX168/100 μg, PEX168/200 μg and placebo, respectively) and vomiting (2.4%, 8.3% and 0% for PEX168/100 μg, PEX168/200 μg and placebo, respectively). Six (1.6%) patients (PEX168/100 μg: N = 2 [1.6%], PEX168/200 μg: N = 3 [2.5%] and placebo: N = 1 [0.8%]) discontinued treatment because of AEs. Four (1.2%) patients (PEX168/100 μg: N = 3 [2.5%] and PEX168/200 μg: N = 1 [0.9%]) developed PEX168 antidrug antibodies. Conclusion PEX168 monotherapy significantly improved glycaemic control in T2D patients with a safety profile resembling that of other glucagon‐like peptide‐1 receptor agonists.

“…31 A post hoc analysis of the SUSTAIN trials revealed that semaglutide was associated with minor reductions or no change in lipid levels across all race and ethnicity subgroups in the SUSTAIN 1 to 7 trials. 32 However, clinical trials on exenatide showed that treatment with exenatide twice-daily or once-weekly significantly improved lipids in Asian and white patients. Asian and white patients showed significant reductions from baseline in the levels of LDL-C and small but statistically significant increases in HDL-C levels (except for Asian patients treated with exenatide onceweekly).…”

Section: Discussionmentioning

confidence: 99%

“…A clinical trial on lixisenatide showed that there were no clinically meaningful changes in lipid variables during the 24‐ and 52‐week treatment periods 31 . A post hoc analysis of the SUSTAIN trials revealed that semaglutide was associated with minor reductions or no change in lipid levels across all race and ethnicity subgroups in the SUSTAIN 1 to 7 trials 32 . However, clinical trials on exenatide showed that treatment with exenatide twice‐daily or once‐weekly significantly improved lipids in Asian and white patients.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of polyethylene glycol loxenatide as add‐on to metformin in patients with type 2 diabetes: A multicentre, randomized, double‐blind, placebo‐controlled, phase 3b trial

Gao

Zhang

et al. 2020

Aim: To assess the efficacy and safety of polyethylene glycol loxenatide (PEX168), a new glucagon-like peptide-1 receptor agonist, as an add-on to metformin therapy in Chinese patients with type 2 diabetes (T2D). Materials and methods: This was a multicentre, randomized, double-blind, placebocontrolled phase 3b trial. After metformin monotherapy (≥1500 mg/day) for 8 weeks or more, patients with uncontrolled T2D (HbA1c of 7.0%-10.5%) from 44 sites were randomized (1:1:1) to metformin + placebo, metformin + PEX168 100 μg, and metformin + PEX168 200 μg. The core treatment period lasted for 24 weeks, followed by a 28-week extension period. The primary endpoint was the change in HbA1c levels at week 24. The main secondary endpoint was the proportion of patients with an HbA1c of less than 7.0% at week 24. Results: The least-square mean (standard error) change in HbA1c levels was significantly greater (P < .001 for superiority) in the PEX168 groups (−1.16% [0.08%] and −1.14% [0.08%] with 100 and 200 μg, respectively) than in the placebo group (0.35% [0.08%]). The proportion of patients with an HbA1c of less than 7.0% at week 24 was significantly higher in the PEX168 100 μg (37.4%) and PEX168 200 μg (40.6%) groups than in the placebo group (16.8%; both P < .001). The gastrointestinal reactions were mild; the risks of hypoglycaemia and weight gain did not increase. Anti-PEX168 antibodies were noted in less than 2% of patients. No treatment-emergent serious adverse events occurred. Conclusion: The subcutaneous injection of PEX168 once a week can effectively, continuously and safely improve HbA1c levels in patients with T2D when combined with metformin.