Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial

• Published in: Diabetes care Vol. 41; no. 2; pp. 258 - 266
• Main Authors: Ahmann, Andrew J., Capehorn, Matthew, Charpentier, Guillaume, Dotta, Francesco, Henkel, Elena, Lingvay, Ildiko, Holst, Anders G., Annett, Miriam P., Aroda, Vanita R.
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.02.2018
• Subjects: Adult; Aged; Aged, 80 and over; Antidiabetics; Blood Glucose - drug effects; Blood Glucose - metabolism; Body weight; Body Weight - drug effects; Clinical trials; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - adverse effects; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Drug Administration Schedule; Drug therapy; Drugs; Evidence-based medicine; Exenatide; Female; Glucagon-Like Peptides - administration & dosage; Glucagon-Like Peptides - adverse effects; Glucose monitoring; Glycated Hemoglobin A - drug effects; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Male; Metformin - administration & dosage; Middle Aged; Peptides - administration & dosage; Peptides - adverse effects; Research design; Safety; Treatment Outcome; Venoms - administration & dosage; Venoms - adverse effects; Weight reduction; Young Adult
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc17-0417

To compare the efficacy and safety of once-weekly semaglutide 1.0 mg s.c. with exenatide extended release (ER) 2.0 mg s.c. in subjects with type 2 diabetes. In this phase 3a, open-label, parallel-group, randomized controlled trial, 813 subjects with type 2 diabetes taking oral antidiabetic drugs were randomized (1:1) to semaglutide 1.0 mg or exenatide ER 2.0 mg for 56 weeks. The primary end point was change from baseline in HbA at week 56. Mean HbA (8.3% [67.7 mmol/mol] at baseline) was reduced by 1.5% (16.8 mmol/mol) with semaglutide and 0.9% (10.0 mmol/mol) with exenatide ER (estimated treatment difference vs. exenatide ER [ETD] -0.62% [95% CI -0.80, -0.44] [-6.78 mmol/mol (95% CI -8.70, -4.86)]; < 0.0001 for noninferiority and superiority). Mean body weight (95.8 kg at baseline) was reduced by 5.6 kg with semaglutide and 1.9 kg with exenatide ER (ETD -3.78 kg [95% CI -4.58, -2.98]; < 0.0001). Significantly more subjects treated with semaglutide (67%) achieved HbA <7.0% (<53 mmol/mol) versus those taking exenatide ER (40%). Both treatments had similar safety profiles, but gastrointestinal adverse events were more common in semaglutide-treated subjects (41.8%) than in exenatide ER-treated subjects (33.3%); injection-site reactions were more frequent with exenatide ER (22.0%) than with semaglutide (1.2%). Semaglutide 1.0 mg was superior to exenatide ER 2.0 mg in improving glycemic control and reducing body weight after 56 weeks of treatment; the drugs had comparable safety profiles. These results indicate that semaglutide treatment is highly effective for subjects with type 2 diabetes who are inadequately controlled on oral antidiabetic drugs.