Safety and efficacy of once-weekly dulaglutide versus sitagliptin after 2years in metformin-treated patients with type 2 diabetes (AWARD-5): A randomized, phase III study

Diabetes, Obesity and Metabolism

Volumn 17, Issue 9, 2015, Pages 849-858

  Weinstock, R S ^a   Guerci, B ^b   Umpierrez, G ^c   Nauck, M A ^d   Skrivanek, Z ^e   Milicevic, Z ^f  

^a SUNY UPSTATE MEDICAL UNIVERSITY   (United States)

^b UNIVERSITÉ DE LORRAINE   (France)

^c EMORY UNIVERSITY   (United States)

^d DIABETESZENTRUM BAD LAUTERBERG   (Germany)

^e ELI LILLY AND COMPANY   (United States)

^f Eli Lilly Regional   (Austria)

Author keywords

Diabetes; Dulaglutide; Sitagliptin

Indexed keywords

DULAGLUTIDE; HEMOGLOBIN A1C; METFORMIN; PLACEBO; SITAGLIPTIN; ANTIDIABETIC AGENT; GLUCAGON LIKE PEPTIDE; GLUCOSE BLOOD LEVEL; GLYCOSYLATED HEMOGLOBIN; HEMOGLOBIN A1C PROTEIN, HUMAN; HYBRID PROTEIN; IMMUNOGLOBULIN FC FRAGMENT;

ABDOMINAL DISTENSION; ABDOMINAL PAIN; ADULT; AGED; ARTHRALGIA; ARTICLE; BACKACHE; CARDIOVASCULAR DISEASE; CLINICAL EFFECTIVENESS; CONTROLLED STUDY; COUGHING; DECREASED APPETITE; DIARRHEA; DISEASE DURATION; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG WITHDRAWAL; DYSPEPSIA; FEMALE; GLYCEMIC CONTROL; HEADACHE; HEMOGLOBIN BLOOD LEVEL; HUMAN; HYPERGLYCEMIA; HYPERSENSITIVITY; INFECTION; INFESTATION; INFLUENZA; INJECTION SITE REACTION; KIDNEY DISEASE; MAJOR CLINICAL STUDY; MALE; MALIGNANT NEOPLASTIC DISEASE; MULTICENTER STUDY; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; PANCREAS DISEASE; PHASE 3 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; THYROID DISEASE; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT PLANNING; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT DISEASE; URINARY TRACT INFECTION; VOMITING; ANALOGS AND DERIVATIVES; BLOOD; CLINICAL TRIAL; COMBINATION DRUG THERAPY; COMPARATIVE STUDY; DIABETES MELLITUS, TYPE 2; DRUG ADMINISTRATION; DRUG EFFECTS; GLUCOSE BLOOD LEVEL; MIDDLE AGED; PROCEDURES; WEIGHT REDUCTION;

BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; DRUG THERAPY, COMBINATION; FEMALE; GLUCAGON-LIKE PEPTIDES; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; HYPOGLYCEMIC AGENTS; IMMUNOGLOBULIN FC FRAGMENTS; MALE; METFORMIN; MIDDLE AGED; RECOMBINANT FUSION PROTEINS; SITAGLIPTIN PHOSPHATE; TREATMENT OUTCOME; WEIGHT LOSS;

EID: 84939565260     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.12479     Document Type: Article

References (35)

1. Glaesner W, Vick AM, Millican R etal. Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein. Diabetes Metab Res Rev 2010; 26: 287-296.
2. Barrington P, Chien JY, Tibaldi F, Showalter HD, Schneck K, Ellis B. LY2189265, a long-acting glucagon-like peptide-1 analogue, showed a dose-dependent effect on insulin secretion in healthy subjects. Diabetes Obes Metab 2011; 13: 434-438.
3. Wysham C, Blevins T, Arakaki R etal. Efficacy and safety of dulaglutide added on to pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes Care 2014; 37: 2159-2167.
4. Umpierrez G, Povedano S, Manghi F, Shurzinske L, Pechtner V. Efficacy and safety of dulaglutide monotherapy vs metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care 2014; 37: 2168-2176.
5. Dungan KM, Povedano ST, Forst T etal. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial. Lancet 2014; 384: 1349-1357.
6. Skrivanek Z, Gaydos B, Chien J etal. Dose-finding results in an adaptive, seamless, randomised trial of once weekly dulaglutide combined with metformin in type 2 diabetes (AWARD-5). Diabetes Obes Metab 2014; 16: 748-756.
7. Nauck M, Weinstock RS, Umpierrez GE, Guerci B, Skrivanek Z, Milicevic Z. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care 2014; 37: 2149-2158.
8. World Medical Association declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997; 277: 925-926.
9. Geiger MJ, Skrivanek Z, Gaydos B, Chien J, Berry S, Berry D. An adaptive, dose-finding, seamless phase 2/3 study of a long-acting glucagon-like peptide-1 analog (dulaglutide): trial design and baseline characteristics. J Diabetes Sci Technol 2012; 6: 1319-1327.
10. Skrivanek Z, Chien J, Gaydos B, Heathman M, Geiger M, Milicevic Z. Dose finding results in an adaptive trial of dulaglutide combined with metformin in type 2 diabetes (AWARD-5). Diabetologia 2013; 56: S402.
11. Skrivanek Z, Berry S, Berry D etal. Application of adaptive design methodology in development of a long-acting glucagon-like peptide-1 analog (dulaglutide): statistical design and simulations. J Diabetes Sci Technol 2012; 6: 1305-1318.
12. Spencer K, Colvin K, Braunecker B etal. Operational challenges and solutions with implementation of an adaptive seamless phase 2/3 study. J Diabetes Sci Technol 2012; 6: 1296-1304.
13. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care 2004; 27: 1487-1495.
14. American Diabetes Association Workgroup on Hypoglycemia. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 2005; 28: 1245-1249.
15. Food and Drug Administration. Novo Nordisk's Liraglutide (injection) for the treatment of patients with type 2 diabetes, NDA 22-341, briefing document: Endocrine and Metabolic Drug Advisory Committee 2 April 2009. 2009. Available from URL: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM148659.pdf. Accessed 12 January 2015.
16. Carpenter J, Kenward M. Chapter 6.5: pattern mixture approach with longitudinal data via MI. Missing Data in Randomised Controlled Trials - a Practical Guide. London: Medical Statistics Unit, London School of Hygiene & Tropical Medicine, 2007. Available from URL: http://www.missingdata.org.uk. Accessed 1 April 2015.
17. Ahren B, Leguizamo Dimas A, Miossec P, Saubadu S, Aronson R. Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin (GetGoal-M). Diabetes Care 2013; 36: 2543-2550.
18. Bergenstal RM, Wysham C, Macconell L etal. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet 2010; 376: 431-439.
19. Schwartz SS. A practice-based approach to the 2012 position statement of the American Diabetes Association and the European Association for the study of diabetes. Curr Med Res Opin 2013; 29: 793-799.
20. Bolli GB, Munteanu M, Dotsenko S etal. Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin (GetGoal-F1). Diabet Med 2014; 31: 176-184.
21. Pratley RE, Nauck M, Bailey T etal. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet 2010; 375: 1447-1456.
22. Nauck M, Frid A, Hermansen K etal. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care 2009; 32: 84-90.
23. Buse JB, Nauck M, Forst T, etal. (2013) Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet 2013; 381: 117-124.
24. Buse JB, Rosenstock J, Sesti G etal. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009; 374: 39-47.
25. Robinson LE, Holt TA, Rees K, Randeva HS, O'Hare JP. Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis. BMJ Open 2013; 3: e001986.
26. Vahle J, Byrd R, Sorden S etal. Evaluation of serum amylase and lipase, and expanded pancreatic histology in monkeys following chronic administration of dulaglutide, a long acting GLP-1 receptor agonist (abstract). NIDDK 2013 Meeting, Pancreatitis-Diabetes-Pancreatic Cancer Workshop. Bethesda, MD, USA.
27. Waser B, Beetschen K, Pellegata NS, Reubi JC. Incretin receptors in non-neoplastic and neoplastic thyroid C cells in rodents and humans: relevance for incretin-based diabetes therapy. Neuroendocrinology 2011; 94: 291-301.
28. Hegedus L, Moses AC, Zdravkovic M, Le Thi T, Daniels GH. GLP-1 and calcitonin concentration in humans: lack of evidence of calcitonin release from sequential screening in over 5000 subjects with type 2 diabetes or nondiabetic obese subjects treated with the human GLP-1 analog, liraglutide. J Clin Endocrinol Metab 2011; 96: 853-860.
29. Bjerre Knudsen L, Madsen LW, Andersen S etal. Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology 2010; 151: 1473-1486.
30. Vahle J, Sorden S, Rosol T etal. Thyroid C-cell morphology, morphometry, and serum calcitonin in male monkeys following twice weekly subcutaneous injection of dulaglutide for 52 weeks (abstract). American College of Toxicology 2013 Meeting. 2013, San Antonio, TX, USA.
31. Byrd R, Sorden S, Ryan T etal. Effects of dulaglutide on calcium chloride stimulated plasma calcitonin and thyroid c-cell mass, hyperplasia, and neoplasia in rats (abstract). American College of Toxicology 2013 Meeting. 2013, San Antonio, TX, USA.
32. Matthews DR, Dejager S, Ahren B etal. Vildagliptin add-on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain: results from a 2-year study. Diabetes Obes Metab 2010; 12: 780-789.
33. Rosenstock J, Cefalu WT, Hollander PA etal. Two-year pulmonary safety and efficacy of inhaled human insulin (Exubera) in adult patients with type 2 diabetes. Diabetes Care 2008; 31: 1723-1728.
34. Macconell L, Pencek R, Li Y, Maggs D, Porter L. Exenatide once weekly: sustained improvement in glycemic control and cardiometabolic measures through 3 years. Diabetes Metab Syndr Obes 2013; 6: 31-41.
35. Garber A, Henry RR, Ratner R etal. Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes. Diabetes Obes Metab 2011; 13: 348-356.