Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial

The Lancet

Volumn 392, Issue 10148, 2018, Pages 637-649

  O'Neil, Patrick M ^a   Birkenfeld, Andreas L ^b   McGowan, Barbara ^c   Mosenzon, Ofri ^d   Pedersen, Sue D ^e   Wharton, Sean ^f   Carson, Charlotte Giwercman ^g   Jepsen, Cecilie Heerdegen ^g   Kabisch, Maria ^g   Wilding, John P H ^h  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^b UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

^c GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

^d HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^e LMC Endocrinology Centre Calgary   (Canada)

^f YORK UNIVERSITY   (Canada)

^g NOVO NORDISK A S   (Denmark)

^h UNIVERSITY OF LIVERPOOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

LIRAGLUTIDE; SEMAGLUTIDE; ANTIDIABETIC AGENT; GLUCAGON LIKE PEPTIDE; GLUCAGON LIKE PEPTIDE 1; GLYCOSYLATED HEMOGLOBIN; PLACEBO;

ADULT; ADVERSE OUTCOME; AGED; ARTICLE; BODY MASS; BODY WEIGHT LOSS; CONSTIPATION; CONTROLLED STUDY; DECREASED APPETITE; DIARRHEA; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG DOSE ESCALATION; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; ERUCTATION; FEMALE; HEADACHE; HUMAN; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAUSEA; OBESITY; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; TREATMENT OUTCOME; VOMITING; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; COMPARATIVE STUDY; GLUCOSE BLOOD LEVEL; MIDDLE AGED; PROCEDURES; SUBCUTANEOUS DRUG ADMINISTRATION;

ADULT; BLOOD GLUCOSE; BODY MASS INDEX; DOUBLE-BLIND METHOD; FEMALE; GLUCAGON-LIKE PEPTIDE 1; GLUCAGON-LIKE PEPTIDES; GLYCATED HEMOGLOBIN A; HUMANS; HYPOGLYCEMIC AGENTS; INJECTIONS, SUBCUTANEOUS; LIRAGLUTIDE; MALE; MIDDLE AGED; OBESITY; PLACEBOS; TREATMENT OUTCOME; WEIGHT LOSS;

EID: 85053840855     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(18)31773-2     Document Type: Article

References (30)

1. Kyle, TK, Dhurandhar, EJ, Allison, DB, Regarding obesity as a disease: evolving policies and their implications. Endocrinol Metab Clin North Am 45 (2016), 511–520.
2. Garvey, WT, Mechanick, JI, Brett, EM, et al. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity: executive summary. Endocr Pract 22 (2016), 842–884.
3. WHO. Obesity: preventing and managing the global epidemic: report of a WHO consultation on obesity. June 3–5, 1997, World Health Organization, Geneva http://apps.who.int/iris/handle/10665/63854. (Accessed 12 July 2018)
4. Bray, GA, Fruhbeck, G, Ryan, DH, Wilding, JP, Management of obesity. Lancet 387 (2016), 1947–1956.
5. Cawley, J, Meyerhoefer, C, The medical care costs of obesity: an instrumental variables approach. J Health Econ 31 (2012), 219–230.
6. World Obesity Federation. World obesity day 2017: global data on costs of consequences. http://www.obesityday.worldobesity.org/ourdata2017. (Accessed 12 July 2018)
7. Bray, GA, Prevention of obesity. https://www.ncbi.nlm.nih.gov/books/NBK279120/. (Accessed 12 July 2018)
8. Mertens, IL, Van Gaal, LF, Overweight, obesity, and blood pressure: the effects of modest weight reduction. Obes Res 8 (2000), 270–278.
9. Warkentin, LM, Das, D, Majumdar, SR, Johnson, JA, Padwal, RS, The effect of weight loss on health-related quality of life: systematic review and meta-analysis of randomized trials. Obes Rev 15 (2014), 169–182.
10. Mann, T, Tomiyama, AJ, Westling, E, Lew, AM, Samuels, B, Chatman, J, Medicare's search for effective obesity treatments: diets are not the answer. Am Psychol 62 (2007), 220–233.
11. Dombrowski, SU, Knittle, K, Avenell, A, Araujo-Soares, V, Sniehotta, FF, Long term maintenance of weight loss with non-surgical interventions in obese adults: systematic review and meta-analyses of randomised controlled trials. BMJ, 348, 2014, g2646.
12. Onakpoya, IJ, Heneghan, CJ, Aronson, JK, Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review. BMC Med, 14, 2016, 191.
13. Flint, A, Raben, A, Astrup, A, Holst, JJ, Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 101 (1998), 515–520.
14. Doyle, ME, Egan, JM, Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther 113 (2007), 546–593.
15. Sorli, C, Harashima, SI, Tsoukas, GM, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol 5 (2017), 251–260.
16. Ahrén, B, Masmiquel, L, Kumar, H, et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol 5 (2017), 341–354.
17. Aroda, VR, Bain, SC, Cariou, B, et al. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol 5 (2017), 355–366.
18. Ware, JE Jr, Sherbourne, CD, The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 30 (1992), 473–483.
19. Seaquist, ER, Anderson, J, Childs, B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 36 (2013), 1384–1395.
20. Food and Agriculture Organization of the UN WHO, United Nations University. Human energy requirements. Report of a joint FAO/WHO/UNU expert consultation. http://www.fao.org/3/a-y5686e.pdf, 2004. (Accessed 12 July 2018)
21. Pi-Sunyer, X, Astrup, A, Fujioka, K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med 373 (2015), 11–22.
22. Rubin, DB, Multiple imputation for nonresponse in surveys. 1987, J Wiley and Sons, New York.
23. Dunnett, CW, A multiple comparison procedure for comparing several treatments with a control. J Am Stat Assoc 50 (1955), 1096–1121.
24. Dunnett, CW, New tables for multiple comparisons with a control. Biometrics 20 (1964), 481–491.
25. Banks, PA, Bollen, TL, Dervenis, C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut 62 (2013), 102–111.
26. Blundell, J, Finlayson, G, Axelsen, M, et al. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab 19 (2017), 1242–1251.
27. Ard, J, Cannon, A, Lewis, CE, et al. Efficacy and safety of liraglutide 3.0 mg for weight management are similar across races: subgroup analysis across the SCALE and phase II randomized trials. Diabetes Obes Metab 18 (2016), 430–435.
28. le Roux, CW, Astrup, A, Fujioka, K, et al. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet 389 (2017), 1399–1409.
29. Fidler, MC, Sanchez, M, Raether, B, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab 96 (2011), 3067–3077.
30. Apovian, CM, Aronne, L, Rubino, D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity 21 (2013), 935–943.