Сахароснижающие препараты и риск развития лекарственно-индуцированного острого панкреатита

Филиппова А.В., Кочетков А.И., Гусенбекова Д.Г., Остроумова О.Д. Сахароснижающие препараты и риск развития лекарственно-индуцированного острого панкреатита. FOCUS Эндокринология. 2021; 2: 52–58. DOI: 10.47407/ef2021.2.2.0025

Filippova A.V., Kochetkov A.I., Gusenbekova D.G., Ostroumova O.D. Antidiabetic drugs and the risk of developing drug-induced acute pancreatitis. FOCUS Endocrinology. 2021; 2: 52–58. DOI: 10.47407/ef2021.2.2.0025

Сахарный диабет 2-го типа (СД 2) – одно из самых распространенных заболеваний во всем мире. Только в России на 2020 г. насчитывается около 5 млн людей с СД. В связи с этим остро стоит вопрос о безопасной и рациональной медикаментозной терапии. Но, как и большинство лекарственных средств (ЛС), препараты для лечения СД имеют ряд нежелательных реакций, к которым относится развитие острого панкреатита (ОП). Цель данного обзора – анализ литературных данных о ЛС, предназначенных для лечения больных СД 2, которые могут приводить к развитию лекарственно-индуцированного острого панкреатита (ЛИОП), и механизмах развития данной патологии на фоне приема конкретных ЛС. С развитием ЛИОП ассоциирован прием бигуанидов (метформин), производных сульфонилмочевины (глибенкламид, глимепирид, гликлазид), инкретин-направленной терапии (эксенатид, ситаглиптин и др.). Литературные данные о развитии ЛИОП представлены в большинстве публикаций описанием отдельных клинических случаев/серии случаев, однако в случае ЛИОП, ассоциированного с приемом производных сульфонилмочевины и инкретин-направленной терапии, имеются данные когортных ретроспективных наблюдательных, проспективных наблюдательных по типу «случай–контроль», рандомизированных контролируемых исследований, метаанализов и субанализов.

Ключевые слова: острый панкреатит, лекарственно-индуцированный панкреатит, лекарственное поражение поджелудочной железы, нежелательные лекарственные реакции, сахарный диабет 2-го типа, пероральные сахароснижающие препараты, ингибиторы дипептидилпептидазы 4-го типа.

Филиппова Анастасия Витальевна - ординатор каф. терапии и полиморбидной патологии, ФГБОУ ДПО РМАНПО
Кочетков Алексей Иванович - канд. мед. наук, доцент каф. терапии и полиморбидной патологии, ФГБОУ ДПО РМАНПО
Гусенбекова Динара Гаджимагомедовна - канд. мед. наук, ассистент каф. терапии и полиморбидной патологии, ФГБОУ ДПО РМАНПО
Остроумова Ольга Дмитриевна - проф., д-р мед. наук, зав. каф. терапии и полиморбидной патологии, ФГБОУ ДПО РМАНПО

1.   Giorda CB, Nada E, Tartaglino B et al. A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position. Diabetes Obes Metab 2014; 16 (11): 1041–7. DOI: 10.1111/dom.12297

2.   Tisdale JE, Miller DA. Drug-induced Diseases: Prevention, Detection, and Management. American Society of Health-System Pharmacists, 2018; p. 877–904.

3.   Inzucchi SE. Metformin and heart failure: innocent until proven guilty. Diabetes Care 2005; 28 (10): 2585–7. DOI: 10.2337/diacare.28.10.2585

4.   Mallick S. Metformin induced acute pancreatitis precipitated by renal failure. Postgrad Med . 2004; 80 (942): 239–40. DOI: 10.1136/pgmj.2003.011957

5.   Fimognari FL, Corsonello A, Pastorell R et al. Metformin-induced pancreatitis: A possible adverse drug effect during acute renal failure. Diabetes Care 2006; 29 (5): 1183. DOI: 10.2337/diacare.2951183

6.   Infante JM, Bermejo AB, Gallardo BP et al. Pancreatitis aguda tóxica por metformina sin insuficiencia renal. Med Clin (Barc) 2008; 131 (13): 519. DOI: 10.1157/13127282

7.   Audia P, Feinfeld DA, Dubrow A, Winchester JF. Metformin-induced lactic acidosis and acute pancreatitis precipitated by diuretic, celecoxib, and candesartan-associated acute kidney dysfunction. Clin Toxicology 2008; 46 (2): 164–66. DOI: 10.1080/15563650701355314/

8.   Golay V, Roychowdhary A. Acute pancreatitis in chronic kidney disease – a common but often misunderstood combination. Ren Fail 2012; 34 (10): 1338–40. DOI: 10.3109/0886022x.2012.718951

9.   Kongsuphol P, Cassidy D, Romeiras F et al. Metformin treatment of diabetes mellitus increases the risk for pancreatitis in patients bearing the CFTR-mutation S573C. Cell Physiol Biochem 2010; 25 (4–5): 389–96. DOI: 10.1159/000303043

10. Gonzalez-Perez A, Schlienger RG, Rodríguez LA. Acute pancreatitis in association with type 2 diabetes and antidiabetic drugs: a population-based cohort study. Diabetes Care 2010; 33 (12): 2580–5. DOI:10.2337/dc10-0842

11. Blomgren KB, Sundström A, Steineck G, Wiholm BE. Obesity and treatment of diabetes with glyburide may both be risk factors for acute pancreatitis. Diabetes Care 2002; 25 (2): 298–302. DOI: 10.2337/diacare.25.2.298

12. Wang T, Wang F, Gou Z et al. Using real-world data to evaluate the association of incretin-based therapies with risk of acute pancreatitis: a meta-analysis of 1,324,515 patients from observational studies. Diabetes Obes Metab 2015; 17 (1): 32–41. DOI: 10.1111/dom.12386

13. Denker PS, Dimarco PE. Exenatide (exendin-4)-induced pancreatitis: a case report. Diabetes Care 2006; 29 (2): 471. DOI: 10.2337/diacare.29.02.06.dc05-2043

14. Cure P, Pileggi A, Alejandro R. Exenatide and rare adverse events. N Engl J Med 2008; 358 (18): 1969–72. DOI: 10.1056/NEJMc0707137

15. Tripathy NR, Basha S, Jain R, Shetty S, Ramachandran A. Exenatide and acute pancreatitis. J Assoc Physicians India 2008; 56: 987–8.

16. Ayoub WA, Kumar AA, Naguib HS, Taylor HC. Exenatide-induced acute pancreatitis. Endocr Pract 2010; 16 (1): 80–3. DOI: 10.4158/EP09104.CRR.

17. Iyer SN, Drake AJ, West RL et al. Case report of acute necrotizing pancreatitis associated with combination treatment of sitagliptin and exenatide. Endocr Pract 2012; 18 (1): 10–3. DOI: 10.4158/EP11264.CR

18. Lee PH, Stockton MD, Franks AS. Acute pancreatitis associated with liraglutide. Ann Pharmacother 2011; 45 (4): 22. DOI: 10.1345/aph.1P714

19. Knezevich E, Crnic T, Kershaw S, Drincic A. Liraglutide-associated acute pancreatitis. Am J Health Syst Pharm 2012; 69 (5): 386–9. DOI: 10.2146/ajhp110221

20. Famularo G, Gasbarrone L, Minisola G. Pancreatitis during treatment with liraglutide. JOP 2012; 13 (5): 540–1. DOI: 10.6092/1590-8577/1107

21. Bourezane H, Kastler B, Kantelip JP. Late and severe acute necrotizing pancreatitis in a patient with liraglutide. Therapie 2012; 67 (6): 539–43. DOI: 10.2515/therapie/2012076

22. Nakata H, Sugitani S, Yamaji S et al. Pancreatitis with pancreatic tail swelling associated with incretin-based therapies detected radiologically in two cases of diabetic patients with end-stage renal disease. Intern Med 2012; 51 (21): 3045–9. DOI: 10.2169/internalmedicine.51.7876

23. Artero A, Bourguet M, Lorente RI, Real JT. Acute pancreatitis in a patient treated with liraglutide. Med Clin (Barc) 2013; 141 (8): 368–9. DOI: 10.1016/j.medcli.2013.01.022

24. Jeyaraj S, Shetty AS, Kumar CR et al. Liraglutide-induced acute pancreatitis. J Assoc Physicians India 2014; 62 (1): 64–6.

25. Garg R, Hussey C, Ibrahim S. Pancreatitis associated with the use of sitagliptin and orlistat combination: a case report. Diabet Med 2010; 27 (4): 485–6. DOI: 10.1111/j.1464-5491.2010.02950.x

26. Sue M, Yoshihara A, Kuboki K et al. A case of severe acute necrotizing pancreatitis after administration of sitagliptin. Clin Med Insights Case Rep 2013; 6: 23–7. DOI: 10.4137/CCRep.S10856

27. Lee CF, Sun MS, Tai YK. Saxagliptin-induced recurrent acute pancreatitis. Intern Med 2014; 53 (12): 1351–4. DOI: 10.2169/internalmedicine.53.1913

28. Girgis CM, Champion BL. Vildagliptin-induced acute pancreatitis. Endocr Pract 2011; 17 (3): 48–50. DOI: 10.4158/EP10383.CR

29. Saraogi R, Mallik R, Ghosh S. Mild acute pancreatitis with vildagliptin use. Indian J Endocrinol Metab 2012; 16 (2): 480–2. DOI: 10.4103/2230-8210.104138

30. US Food and Drug Administration. Information for Healthcare Professionals: Exenatide (marketed as Byetta) – 8/2008 Update. 2008. www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafety. Date of access: 20.06.2021.

31. Department of Health and Human Services, US Food and Drug Administration, Center for Drug Evaluation and Research. Application. 2018. www .accessdata.fda.gov/drugsatfda_docs/nda/2009/0219195000sumr. Date of access: 20.06.2021.

32. Neumiller JJ. Incretin-based therapies. Med Clin North Am 2015; 99 (1): 107–29. DOI: 10.1016/j.mcna.2014.08.013

33. de Heer J, Göke B. Are incretin mimetics and enhancers linked to pancreatitis and malignant transformations in pancreas? Expert Opin Drug Saf 2014; 13 (11): 1469–81. DOI: 10.1517/14740338.2014.955013

34. Elashoff M, Matveyenko AV, Gier B et al. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 2011; 141 (1): 150–6. DOI: 10.1053/j.gastro.2011.02.018

35. Cohen D. Reports of pancreatitis are 20-30 times more likely with GLP-1 drugs, analysis finds. BMJ 2013; 23 (346): 2607. DOI: 10.1136/bmj.f2607

36. Delfino M, Motola D, Benini A et al. Incretin-mimetics associated pancreatitis: evidence from the spontaneous adverse drug reactions reporting in Italy. Expert Opin Drug Saf 2014; 13 (2): 151–6. DOI: 10.1517/14740338.2014.853036

37. Singh S, Chang HY, Richards TM et al. 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 (7): 534–9. DOI: 10.1001/jamainternmed.2013.2720

38. Raz I, Bhatt DL, Hirshberg B et al. Incidence of pancreatitis and pancreatic cancer in a randomized controlled multicenter trial (SAVOR-TIMI 53) of the dipeptidyl peptidase-4 inhibitor saxagliptin. Diabetes Care 2014; 37 (9): 2435–41. DOI: 10.2337/dc13-2546

39. White WB, Cannon CP, Heller SR et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013; 369 (14): 1327–35. DOI: 10.1056/NEJMoa1305889

40. Green JB, Bethel MA, Armstrong PW et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2015; 373 (3): 232–42. DOI: 10.1056/NEJMoa1501352

41. Scirica BM, Bhatt DL, Braunwald E et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013; 369 (14): 1317–26. DOI: 10.1056/NEJMoa1307684

42. Tkáč I, Raz I. Combined Analysis of Three Large Interventional Trials With Gliptins Indicates Increased Incidence of Acute Pancreatitis in Patients With Type 2 Diabetes. Diabetes Care 2017; 40 (2): 284–6. DOI: 10.2337/dc15-1707

43. Hong J, Buse JB, Funk MJ et al. The Risk of Acute Pancreatitis After Initiation of Dipeptidyl Peptidase 4 Inhibitors: Testing a Hypothesis of Subgroup Differences in Older U.S. Adults. Diabetes Care 2018; 41 (6): 1196–3. DOI: 10.2337/dc17-2212

44. Kim YG, Kim S, Han SJ et al. Dipeptidyl Peptidase-4 Inhibitors and the Risk of Pancreatitis in Patients with Type 2 Diabetes Mellitus: A Population-Based Cohort Study. J Diabetes Res 2018. ID-5246976. DOI: 10.1155/2018/5246976

45. 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 2015; 373 (1): 11–22. DOI: 10.1056/nejmoa1411892

46. Steinberg WM, Rosenstock J, Wadden TA et al. Impact of Liraglutide on Amylase, Lipase, and Acute Pancreatitis in Participants With Overweight/Obesity and Normoglycemia, Prediabetes, or Type 2 Diabetes: Secondary Analyses of Pooled Data From the SCALE Clinical Development Program. Diabetes Care 2017; 40 (7): 839–48. DOI: 10.2337/dc16-2684

47. Steinberg WM, Buse JB, Ghorbani MLM et al. Amylase, Lipase, and Acute Pancreatitis in People With Type 2 Diabetes Treated With Liraglutide: Results From the LEADER Randomized Trial. Diabetes Care 2017; 40 (7): 966–72. DOI: 10.2337/dc16-2747

48. Nauck MA, Meier JJ, Schmidt WE. Incretin-based glucose-lowering medications and the risk of acute pancreatitis and/or pancreatic cancer: Reassuring data from cardio-vascular outcome trials. Diabetes Obes Metab 2017; 19 (9): 1327–8. DOI: 10.1111/dom.12981

49. Li X, Zhang Z, Duke J. Glucagon-like peptide 1-based therapies and risk of pancreatitis: a self-controlled case series analysis. Pharmacoepidemiol Drug Saf 2014; 23 (3): 234–9. DOI: 10.1002/pds.3542

50. Giorda CB, Picariello R, Nada E et al. Incretin therapies and risk of hospital admission for acute pancreatitis in an unselected population of European patients with type 2 diabetes: a case-control study. Lancet Diabetes Endocrinol 2014; 2 (2): 111–5. DOI: 10.1016/S2213-8587(13)70147-5

51. Faillie JL, Azoulay L, Patenaude V et al. Incretin based drugs and risk of acute pancreatitis in patients with type 2 diabetes: cohort study. BMJ 2014; 348 (24): 2780. DOI: 10.1136/bmj.g2780

52. Chou HC, Chen WW, Hsiao FY. Acute pancreatitis in patients with type 2 diabetes mellitus treated with dipeptidyl peptidase-4 inhibitors: a population-based nested case-control study. Drug Saf 2014; 37 (7): 521–8. DOI: 10.1007/s40264-014-0171-x

53. Funch D, Gydesen H, Tornøe K et al. A prospective, claims-based assessment of the risk of pancreatitis and pancreatic cancer with liraglutide compared to other antidiabetic drugs. Diabetes Obes Metab 2014; 16 (3): 273–5. DOI: 10.1111/dom.12230

54. Eurich DT, Simpson S, Senthilselvan A et al. Comparative safety and effectiveness of sitagliptin in patients with type 2 diabetes: retrospective population based cohort study. BMJ 2013; 346 (25): 2267. DOI: 10.1136/bmj.f2267

55. Dore DD, Hussein M, Hoffman C et al. A pooled analysis of exenatide use and risk of acute pancreatitis. Curr Med Res Opin 2013; 29 (12): 1577–86. DOI: 10.1185/03007995.2013.838550

56. 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 (11): 1412–8. DOI: 10.1111/j.1464-5491.2012.03652.x

57. Romley JA, Goldman DP, Solomon M et al. Exenatide therapy and the risk of pancreatitis and pancreatic cancer in a privately insured population. Diabetes Technol Ther 2012; 14 (10): 904–11. DOI: 10.1089/dia.2012.0075

58. Dore DD, Bloomgren GL, Wenten M et al. A cohort study of acute pancreatitis in relation to exenatide use. Diabetes Obes Metab 2011; 13 (6): 559–66. DOI: 10.1111/j.1463-1326.2011.01376.x

59. 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 (11): 2349–54. DOI: 10.2337/dc10-0482

60. 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 to metformin or glyburide. Curr Med Res Opin 2009; 25 (4): 1019–27. DOI: 10.1185/03007990902820519

61. Monami M, Dicembrini I, Mannucci E. Dipeptidyl peptidase-4 inhibitors and pancreatitis risk: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2014; 16 (1): 48–56. DOI: 10.1111/dom.12176

62. Li L, Shen J, Bala MM et al. Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus: systematic review and meta-analysis of randomised and non-randomised studies. BMJ 2014; 348 (2): 2366. DOI: 10.1136/bmj.g2366

63. Alves C, Batel-Marques F, Macedo AF. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer. Diabetes Res Clin Pract 2012; 98 (2): 271–84. DOI: 10.1016/j.diabres.2012.09.008

64. Meier JJ, Nauck MA. Risk of pancreatitis in patients treated with incretin-based therapies. Diabetologia 2014; 57 (7): 1320-4. DOI: 10.1007/s00125-014-3231-y

65. Engel SS, Williams-Herman DE, Golm GT et al. Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis. Int J Clin Pract 2010; 64 (7): 984-90. DOI: 10.1111/j.1742-1241.2010.02382.x

66. Ligueros-Saylan M, Foley JE, Schweizer A, Couturier A, Kothny W. An assessment of adverse effects of vildagliptin versus comparators on the liver, the pancreas, the immune system, the skin and in patients with impaired renal function from a large pooled database of Phase II and III clinical trials. Diabetes Obes Metab 2010; 12 (6): 495–9. DOI: 10.1111/j.1463-1326.2010.01214.x

67. MacConell L, Brown C, Gurney K, Han J. Safety and tolerability of exenatide twice daily in patients with type 2 diabetes: integrated analysis of 5594 patients from 19 placebo-controlled and comparator-controlled clinical trials. Diabetes Metab Syndr Obes 2012; 5: 29–41. DOI: 10.2147/DMSO.S28387

68. MacConell L, Gurney K, Malloy J et al. Safety and tolerability of exenatide once weekly in patients with type 2 diabetes: an integrated analysis of 4,328 patients. Diabetes Metab Syndr Obes 2015; 8: 241–53. DOI: 10.2147/DMSO.S77290

69. Hou Y, Ernst SA, Heidenreich K, Williams JA. Glucagon-like peptide-1 receptor is present in pancreatic acinar cells and regulates amylase secretion through cAMP. Am J Physiol Gastrointest Liver Physiol 2016; 310 (1): 26–33. DOI: 10.1152/ajpgi.00293.2015

70. Koehler JA, Baggio LL, Cao X et al. Glucagon-like peptide-1 receptor agonists increase pancreatic mass by induction of protein synthesis. Diabetes 2015; 64 (3): 1046–56. DOI: 10.2337/db14-0883

71. Gotfredsen CF, Mølck AM, Thorup I et al. The human GLP-1 analogs liraglutide and semaglutide: absence of histopathological effects on the pancreas in nonhuman primates. Diabetes 2014; 63 (7): 2486–97. DOI: 10.2337/db13-1087

72. Bonner-Weir S, In't Veld PA, Weir GC. Reanalysis of study of pancreatic effects of incretin therapy: methodological deficiencies. Diabetes Obes Metab 2014; 16 (7): 661–6. DOI: 10.1111/dom.12257

73. Ueberberg S, Jütte H, Uhl W et al. Histological changes in endocrine and exocrine pancreatic tissue from patients exposed to incretin-based therapies. Diabetes Obes Metab 2016; 18 (12): 1253–62. DOI: 10.1111/dom.12766

74. Smits MM, Tonneijck L, Muskiet MH et al. Pancreatic Effects of Liraglutide or Sitagliptin in Overweight Patients With Type 2 Diabetes: A 12-Week Randomized, Placebo-Controlled Trial. Diabetes Care 2017; 40 (3): 301–8. DOI: 10.2337/dc16-0836

75. Tanaka K, Saisho Y, Manesso E et al. Effects of Liraglutide Monotherapy on Beta Cell Function and Pancreatic Enzymes Compared with Metformin in Japanese Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Subpopulation Analysis of the KIND-LM Randomized Trial. Clin Drug Investig 2015; 35 (10): 675–84. DOI: 10.1007/s40261-015-0331-5

76. Saisho Y. Incretin-based therapy and pancreatitis: accumulating evidence and unresolved questions. Ann Transl Med 2018; 6 (7): 131. DOI: 10.21037/atm.2018.02.24

77. Marso SP, Daniels GH, Brown-Frandsen K et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016; 375 (4): 311–22. DOI: 10.21037/atm.2018.02.24.10.1056/NEJMoa1603827

78. Yazbeck R, Howarth GS, Abbott CA. Dipeptidyl peptidase inhibitors, an emerging drug class for inflammatory disease? Trends Pharmacol Sci 2009; 30 (11): 600–7. DOI: 10.1016/j.tips.2009.08.003

79. Attaway A, Mersfelder TL, Vaishnav S, Baker JK. Bullous pemphigoid associated with dipeptidyl peptidase IV inhibitors. A case report and review of literature. J Dermatol Case Rep 2014; 8 (1): 24–8. DOI: 10.3315/jdcr.2014.1166

80. Ujiie H, Muramatsu K, Mushiroda T et al. HLA-DQB1*03:01 as a Biomarker for Genetic Susceptibility to Bullous Pemphigoid Induced by DPP-4 Inhibitors. J Invest Dermatol 2018; 138 (5): 1201–4. DOI: 10.1016/j.jid.2017.11.023

81. Egan AG, Blind E, Dunder K et al. Pancreatic safety of incretin-based drugs--FDA and EMA assessment. N Engl J Med–2014; 370 (9): 794–7. DOI: 10.1056/NEJMp1314078

82. Филиппова А.В., Остроумова О.Д. Лекарственно-индуцированный панкреатит: фокус на препараты, применяющиеся для лечения заболеваний сердечно-сосудистой системы. Медицинский алфавит. 2021; 7: 42–7.

[Filippova A.V., Ostroumova O.D. Drug-induced pancreatitis: focus on drugs used to treat diseases of the cardiovascular system. Medical Alphabet. 2021; 7: 42–7 (in Russian).]

83. Остроумова О.Д., Качан В.О. Лекарственно-индуцированный панкреатит. Лечебное дело. 2020; 3:14–25. DOI: 10.24412/2071-5315-2020-12251

[Ostroumova O.D., Kachan V.O. Drug-induced pancreatitis. Medical Business. 2020; 3: 14–24. DOI: 10.24412/2071–5315–2020–12251 (in Russian).]