Once-Weekly Semaglutide Improved Glycemic Control in Type 2 Diabetes
Semaglutide yielded better outcomes in type 2 diabetes than insulin glargine.
ORLANDO, Fla. — Treatment with a semaglutide — a once-weekly, subcutaneous, glucagon-like peptide 1 (GLP-1) receptor agonist — improved glycemic control and body weight more than treatment with insulin glargine in patients with type 2 diabetes treated with metformin and/or a sulfonylurea, according to results from the SUSTAIN 4 trial.
Researchers reported the findings from the phase 3a, open-label study at the American Association of Clinical Endocrinologists (AACE) 25th Annual Scientific & Clinical Congress.
The study included 1089 adults with type 2 diabetes who were on stable metformin with or without a sulfonylurea. Patients were randomly assigned to semaglutide 0.5 mg (n=362) or 1.0 mg (n=362) once weekly or once daily insulin glargine (n=365), with a starting dose of 10 units per day, for 30 weeks. Fifty-one percent of patients in both semaglutide groups and 52% of patients in the insulin glargine group were on metformin plus a sulfonylurea. Researchers titrated to a pre-breakfast self-monitored plasma glucose target of 4.0 mmol/L to 5.5 mmol/L.
After 30 weeks, mean HbA1c, which was 8.2% at baseline, decreased by 1.2% and 1.6% in the semaglutide 0.5-mg and 1.0-mg groups, respectively, as compared with 0.8% in the insulin glargine group. Estimated treatment difference for semaglutide vs insulin glargine were –0.38% and –0.81%; P<.0001 for both).
Results also showed that more patients in the semaglutide 0.5-mg group (57.5%) and semaglutide 1.0-mg group (73.3%), as compared with the insulin glargine group (38.1%), achieved an HbA1c of less than 7%. Similar results were seen for patients achieving an HbA1c of 6.5% or less (37.3% and 54.2% vs 17.5%, respectively).
In terms of mean fasting plasma glucose, which was 9.7 mmol/L at baseline, data linked semaglutide 0.5 mg and 1.0 mg and insulin glargine to decreases of 2.1 mmol/L, 2.7 mmol/L, and 2.1 mmol/L, respectively. Estimated treatment differences were 0.07 mmol/L (P=.7) and –0.61 mmol/L (P=.0002). Mean 8-point self-monitored plasma glucose decreased by 2.4 mmol/L, 2.9 mmol/L, and 2.4 mmol/L, respectively. Estimated treatment differences were –0.07 mmol/L (P=.6) and –0.58 mmol/L (P<.0001).
Mean body weight was reduced by 3.5 kg and 5.2 kg in the semaglutide 0.5-mg and 1.0-mg groups, respectively, while it increased by 1.2 kg in the insulin glargine group. Estimated treatment differences were –4.62 kg and –6.34 kg (P<.0001 for both).
The researchers also assessed overall treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire. With semaglutide 0.5 mg and 1.0 mg and insulin glargine, scores improved by 4.9, 5.4, and 4.0 points, respectively. Estimated treatment differences were 0.87 (P=.025) and 1.38 (P=.0005).
Adverse events were reported in 69.9%, 73.3%, and 65.3% of the semaglutide 0.5-mg, semaglutide 1.0-mg, and insulin glargine groups, respectively. Serious adverse events were reported in 6.1%, 4.7%, and 5.0% of the groups, respectively, and fatal adverse events occurred in 4 patients treated with semaglutide and 2 treated with insulin glargine. Discontinuation related to adverse events occurred in 5.5%, 7.5%, and 1.1% of the patients, respectively.
Mild gastrointestinal issues were the most commonly reported adverse events with semaglutide.
Severe hypoglycemia, as confirmed by blood glucose, was reported by 4.4%, 5.6%, and 10.6%, of patients in the semaglutide 0.5-mg, semaglutide 1.0-mg, and insulin glargine groups, respectively.
“Semaglutide … provided superior glycemic control and body weight reduction vs insulin glargine in patients with type 2 diabetes treated with metformin with or without a sulfonylurea,” the researchers wrote.
Several study authors are employees of Novo Nordisk.
- Aroda V, Bain S, Cariou B, et al. Abstract 290. Efficacy and Safety of Once-Weekly Semaglutide vs Once-Daily Insulin Glargine in Insulin-Naïve Subjects With Type 2 Diabetes (SUSTAIN 4). Presented at: AACE 25th Annual Scientific & Clinical Congress; May 25-29, 2016; Orlando, FL.