SUSTAIN 10: Efficacy and Safety of Semaglutide 1.0 mg Once Weekly versus Liraglutide 1.2 mg Once Daily - European Medical Journal

SUSTAIN 10: Efficacy and Safety of Semaglutide 1.0 mg Once Weekly versus Liraglutide 1.2 mg Once Daily

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*Matthew S Capehorn,1 Andrei-Mircea Catarig,2 Julie K Furberg,2 Andrej Janez,3 Hermione C Price,4 Sayeh Tadayon,2 Bruno Vergès,5 Michel Marre6

Dr Capehorn reports being an unpaid board member of the Association for the Study of Obesity (ASO) and the Primary Care Academy of Diabetes Specialists (PCADS), an expert advisor to The National Institute for Health and Care Excellence (NICE), a part-time Medical Director at LighterLife (a commercial weight-loss company), a partner at Clifton Medical Centre, and director at RIO Weight Management, Ltd; he also reports research income/support from Abbott, Boehringer Ingelheim/Lilly, GSK, Leo, Novartis, and Novo Nordisk; Advisory Board support from Boehringer Ingelheim/Lilly, Janssen, Merck Sharp & Dohme, and Novo Nordisk; and speaker fees from Boehringer Ingelheim/Lilly, Janssen, and Novo Nordisk. Dr Catarig is a Novo Nordisk employee, and his wife is an employee of Novo Nordisk Region Europe Pharmaceuticals A/S. Dr Furberg is a Novo Nordisk employee and shareholder. Dr Tadayon is a Novo Nordisk employee. Dr Janez and Dr Vergès report no conflicts of interest. Dr Price reports that her institute was a trial site for the SUSTAIN 10 clinical trial (funded by Novo Nordisk); she also reports grants and personal fees from Novo Nordisk; and personal fees from AstraZeneca, Boehringer Ingelheim, Lilly, Merck Sharp & Dohme, and Sanofi. Dr Marre reports personal fees from Merck Sharp & Dohme, Novo Nordisk, and Servier; and grants from Bayer and Sanofi; he also reports being the president of a not-for-profit institution named Fondation Francophone pour la Recherche sur le Diabète (supported by grants from Abbott, AstraZeneca, Merck Sharp & Dohme, Novo Nordisk, Roche, and Sanofi).


This study was funded by Novo Nordisk. The authors thank Dr Tadayon from Novo Nordisk for her review and input to this summary, and Ms Flavia Sciota, PhD (AXON Communications) for medical writing and editorial assistance (funded by Novo Nordisk).

EMJ Diabet.. ;7[1]:53-55. Abstract No AR04.
Body weight, clinical practice, glucagon-like peptide-1 receptor agonist (GLP-1RA), glycaemic control, liraglutide, semaglutide, SUSTAIN, Type 2 diabetes mellitus (T2DM)

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

Subcutaneous semaglutide once weekly (OW) and subcutaneous liraglutide once daily (OD) are two glucagon-like peptide-1 receptor agonists (GLP-1RA) approved for the treatment of Type 2 diabetes mellitus (T2DM).1,2 Both drugs decreased HbA1c, reduced body weight, and provided cardiovascular benefits in pivotal Phase III trials.3 Given the positive efficacy profiles and recent recommendations from international associations,4,5 both semaglutide and liraglutide are GLP-1RA that clinicians may consider prescribing to patients with T2DM; the clinical decision making involves choosing between an established OD formulation and a recently approved OW formulation that may be perceived as more convenient. Comparative head-to-head data would help resolve this clinical prescribing dilemma and provide evidence relevant to clinical practice. However, prior to the SUSTAIN 10 clinical trial, a Europe-based head-to-head comparison of the two drugs had not been conducted. SUSTAIN 10 compared the efficacy and safety of semaglutide 1.0 mg OW with that of liraglutide 1.2 mg OD. The doses were chosen to represent the most common (liraglutide 1.2 mg)6 and the anticipated most common (semaglutide 1.0 mg) prescription patterns in Europe and, thereby, increase the clinical relevance of the results.

This Phase IIIb, 30-week, open-label trial was conducted in 11 European countries and included 577 subjects with T2DM inadequately controlled with 1–3 antidiabetic drugs, i.e., metformin, sulphonylurea, and sodium–glucose cotransporter-2 inhibitors. Subjects were randomised 1:1 to subcutaneous semaglutide 1.0 mg OW or subcutaneous liraglutide 1.2 mg OD.

The primary and confirmatory secondary endpoints were, respectively, change from baseline to Week 30 in HbA1c and body weight. Other efficacy endpoints, together with safety and patient-reported outcomes, were  also assessed.

The main results are shown in Table 1. Semaglutide was superior to liraglutide for the primary and confirmatory secondary endpoints: from baseline to Week 30, HbA1c decreased by 1.7%-point versus 1.0%-point (baseline 8.2%), and weight decreased by 5.8 kg versus 1.9 kg (baseline 96.9 kg), with semaglutide versus liraglutide, respectively (both p<0.0001). The proportions of subjects achieving HbA1c targets (<7.0% and ≤6.5%), weight-loss responses (≥5% and ≥10%), and clinically important composite endpoints were higher with semaglutide versus liraglutide (p<0.0001 for all). Similar results were seen with other glycaemic and weight parameters. Treatment satisfaction (as measured by the Diabetes Treatment Satisfaction Questionnaire [status version] summary score) improved with both treatments (estimated treatment difference 0.63; p=0.0814), and although statistical significance was not reached with all parameters, the data favoured semaglutide versus liraglutide.

Table 1: Key primary and secondary endpoints in SUSTAIN 10.
BG: blood glucose; CI: confidence interval; ETD: estimated treatment difference; FPG: fasting plasma glucose; HbA1C: haemoglobin A1C; OR: odds ratio; SMBG: self-measured blood glucose.

Safety profiles were generally similar with both treatments, except that higher proportions of subjects with semaglutide versus liraglutide experienced gastrointestinal adverse events (AE): nausea: 21.8% versus 15.7%; diarrhoea: 15.6% versus 12.2%; vomiting: 10.4% versus 8.0% and AE leading to treatment discontinuation (11.6% versus 6.6%; driven by gastrointestinal AE). These findings are consistent with the known safety profile of GLP-1RA: the most common AE observed with this class are gastrointestinal.7

In summary, SUSTAIN 10 confirmed that both treatments were effective in reducing HbA1c and body weight in subjects with T2D, and demonstrated superior efficacy with semaglutide 1.0 mg OW compared with liraglutide 1.2 mg OD. Both treatments were generally well-tolerated. These findings are consistent with those from the SUSTAIN 3 and 7 trials, which compared semaglutide with other GLP-1RA (exenatide extended release and dulaglutide, respectively).8,9 In conclusion, the SUSTAIN 10 results support semaglutide as a favourable treatment option in clinical practice.

Novo Nordisk. Ozempic® (semaglutide) Summary of Product Characteristics, 2018. Available at: Last accessed: 30 September 2019. Novo Nordisk. Victoza® (liraglutide) Summary of Product Characteristics, 2019. Available at: Accessed 30 September 2019. Knudsen LB, Lau J. The discovery and development of liraglutide and semaglutide.Front Endocrinol. 2019;10:155. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: Standards of medical care in Diabetes – 2019. Diabetes Care. 2019;42(Suppl 1):S90-102. Davies MJ et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018;41(12):2669-701. Ostawal A et al. Clinical effectiveness of liraglutide in type 2 diabetes treatment in the real-world setting: A systematic literature review. Diabetes Ther. 2016;7(3):411-38. Lyseng-Williamson KA. Glucagon-like peptide-1 receptor analogues in type 2 diabetes: Their use and differential features. Clin Drug Investig. 2019;39(8):805-19. Ahmann AJ et al. 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. Diabetes Care. 2018;41(2):258-66. Pratley RE et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): A randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018; 6(4):275-86.

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