Assessment of pancreas safety in the development program of once-weekly GLP-1 receptor agonist dulaglutide

Diabetes Care

Volumn 40, Issue 5, 2017, Pages 647-654

  Nauck, Michael A ^a   Frossard, Jean Louis ^b   Barkin, Jamie S ^c   Anglin, Greg ^d   Hensley, Ingrid E ^d   Harper, Kristine D ^d   Milicevic, Zvonko ^d  

^a ST JOSEF HOSPITAL   (Germany)

^b GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^c UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^d ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA AMYLASE PANCREAS ISOENZYME; DULAGLUTIDE; EXENDIN 4; INSULIN GLARGINE; METFORMIN; PLACEBO; SITAGLIPTIN; TRIACYLGLYCEROL LIPASE; ANTIDIABETIC AGENT; GLUCAGON LIKE PEPTIDE; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; HYBRID PROTEIN; IMMUNOGLOBULIN FC FRAGMENT; PEPTIDE; VENOM;

ABDOMINAL PAIN; ACUTE PANCREATITIS; ARTICLE; DRUG EFFECT; DRUG EXPOSURE; DRUG SAFETY; HUMAN; INCIDENCE; MAJOR CLINICAL STUDY; NON INSULIN DEPENDENT DIABETES MELLITUS; PANCREAS CANCER; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK ASSESSMENT; TREATMENT DURATION; ACUTE DISEASE; AGONISTS; ANALOGS AND DERIVATIVES; CHEMICALLY INDUCED; DIABETES MELLITUS, TYPE 2; FEMALE; MALE; MIDDLE AGED; PANCREATITIS;

ACUTE DISEASE; DIABETES MELLITUS, TYPE 2; FEMALE; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR; GLUCAGON-LIKE PEPTIDES; HUMANS; HYPOGLYCEMIC AGENTS; IMMUNOGLOBULIN FC FRAGMENTS; INSULIN GLARGINE; MALE; METFORMIN; MIDDLE AGED; PANCREATITIS; PEPTIDES; RECOMBINANT FUSION PROTEINS; SITAGLIPTIN PHOSPHATE; VENOMS;

EID: 85019350081     PISSN: 01495992     EISSN: 19355548     Source Type: Journal    
DOI: 10.2337/dc16-0984     Document Type: Article

References (40)

1. Buse JB, Rosenstock J, Sesti G, et al.; LEAD-6 Study Group. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, openlabel trial (LEAD-6). Lancet 2009;374:39-47
2. Drucker DJ, Buse JB, Taylor K, et al.; DURATION-1 Study Group. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 2008;372:1240-1250
3. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007;132:2131-2157
4. Gigoux V, Fourmy D. Acting on hormone receptors with minimal side effect on cell proliferation: a timely challenge illustrated with GLP-1R and GPER. Front Endocrinol (Lausanne) 2013;4:50
5. Ahmad SR, Swann J. Exenatide and rare adverse events. N Engl JMed 2008;358:1970-1971
6. Denker PS, Dimarco PE. Exenatide (exendin-4)-induced pancreatitis: a case report. Diabetes Care 2006;29:471
7. Dore DD, Seeger JD, Arnold Chan K. Use of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared tometformin or glyburide. Curr Med Res Opin 2009;25:1019-1027
8. Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 2011;141:150-156
9. Jensen TM, Saha K, Steinberg WM. Is there a link between liraglutide and pancreatitis? A post hoc review of pooled and patient-level data from completed liraglutide type 2 diabetes clinical trials. Diabetes Care 2015;38:1058-1066
10. Gale EA. Smoke or fire? Acute pancreatitis and the liraglutide trials. Diabetes Care 2015;38:948-950
11. Girman CJ, Kou TD, Cai B, et al. Patients with type 2 diabetes mellitus have higher risk for acute pancreatitis compared with those without diabetes. Diabetes Obes Metab 2010;12:766-771
12. Dore DD, Bloomgren GL, Wenten M, et al. A cohort study of acute pancreatitis in relation to exenatide use. Diabetes Obes Metab 2011;13:559-566
13. Wenten M, Gaebler JA, Hussein M, et al. Relative risk of acute pancreatitis in initiators of exenatide twice daily compared with other anti-diabetic medication: a follow-up study. Diabet Med 2012;29:1412-1418
14. Garg R, Chen W, Pendergrass M. Acute pancreatitis in type 2 diabetes treated with exenatide or sitagliptin: a retrospective observational pharmacy claims analysis. Diabetes Care 2010;33:2349-2354
15. Singh S, Chang HY, Richards TM, Weiner JP, Clark JM, Segal JB. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med 2013;173:534-539
16. 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
17. Meier JJ, Nauck MA. Risk of pancreatitis in patients treated with incretin-based therapies. Diabetologia 2014;57:1320-1324
18. Egan AG, Blind E, Dunder K, et al. Pancreatic safety of incretin-based drugs-FDA and EMA assessment. N Engl J Med 2014;370:794-797
19. Trulicity [package insert]. Indianapolis, IN, Eli Lilly & Co, 2017
20. Dungan KM, Povedano ST, Forst T, et al. Onceweekly 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
21. Umpierrez G, Tofé Povedano S, Pérez Manghi F, Shurzinske L, Pechtner V. Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care 2014;37:2168-2176
22. Wysham C, Blevins T, Arakaki R, et al. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes Care 2014;37:2159-2167
23. Terauchi Y, Satoi Y, Takeuchi M, Imaoka T. Monotherapy with the once weekly GLP-1 receptor agonist dulaglutide for 12 weeks in Japanese patients with type 2 diabetes: dosedependent effects on glycaemic control in a randomised, double-blind, placebo-controlled study. Endocr J 2014;61:949-959
24. Skrivanek Z, Gaydos BL, Chien JY, et al. Dose-finding results in an adaptive, seamless, randomized trial of once-weekly dulaglutide combined with metformin in type 2 diabetes patients (AWARD-5). Diabetes Obes Metab 2014;16:748-756
25. Frossard JL, Steer ML, Pastor CM. Acute pancreatitis. Lancet 2008;371:143-152
26. Banks PA, Freeman ML; Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006;101:2379-2400
27. MSSO. Introductory Guide for Standardised MedDRA Queries (SMQs) Version 15.0 [Internet]. March 2012. Available from: http://www.meddra.org/sites/default/files/guidance/file/smq-intguide-15-0-english.pdf. Accessed 16 February 2015
28. Byetta [package insert]. Princeton, NJ, Bristol-Myers Squibb Company and Wilmington, DE, AstraZeneca Pharmaceuticals LP, 2015
29. Victoza [package insert]. Princeton, NJ, Novo Nordisk, 2016
30. Josse RG. Update on TECOS Safety Data: Hypoglycemia, Pancreatitis and Pancreatic Cancer [article online], 2015. Available from http://www.easdvirtualmeeting.org/resources/updateontecos-safety-data. Accessed November 1, 2015
31. Abbas AS, Dehbi H-M, Ray KK. Cardiovascular and non-cardiovascular safety of dipeptidyl peptidase-4 inhibition: a meta-analysis of randomized controlled cardiovascular outcome trials. Diabetes Obes Metab 2016;18:295-299
32. Kelly TR. Gallstone pancreatitis. Local predisposing factors. Ann Surg 1984;200:479-485
33. Usborne A, Byrd RA, Meehan J, et al. An investigative study of pancreatic exocrine biomarkers, histology, and histomorphometry in male Zucker diabetic fatty (ZDF) rats given dulaglutide by subcutaneous injection twice weekly for 13 weeks. Toxicol Pathol 2015;43:1093-1102
34. Steinberg WM, Nauck MA, Zinman B, et al.; LEADER Trial investigators. LEADER 3-lipase and amylase activity in subjects with type 2 diabetes: baseline data fromover 9000 subjects in the LEADER Trial. Pancreas 2014;43:1223-1231
35. Pratley RE, Nauck MA, Barnett AH, et al.; HARMONY 7 study group. Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study. Lancet Diabetes Endocrinol 2014;2:289-297
36. Steinberg WM, De Vries JH, Wadden TA, Jensen CB, Svendsen CB, Rosenstock J. Tu1502 longitudinal monitoring of lipase and amylase in adults with type 2 diabetes and obesity: evidence from two phase 3 randomized clinical trials with once daily GLP-1 analog liraglutide. Gastroenterology 2012;142(Suppl. 1): S-850-S-851
37. Chandra R, Liddle RA. Neural and hormonal regulation of pancreatic secretion. Curr Opin Gastroenterol 2009;25:441-446
38. Baggio LL, Huang Q, Cao X, Drucker DJ. An albumin-exendin-4 conjugate engages central and peripheral circuits regulating murine energy and glucose homeostasis. Gastroenterology 2008;134:1137-1147
39. Gier B, Matveyenko AV, Kirakossian D, Dawson D, Dry SM, Butler PC. Chronic GLP-1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the Kras (G12D) mouse model. Diabetes 2012;61:1250-1262
40. Williams JA. GLP-1 mimetic drugs and the risk of exocrine pancreatic disease: cell and animal studies. Pancreatology 2016;16:2-7