Dyspeptic syndrome associated with antidiabetic therapy

Czech version

Authors: A. Šmahelová
Authors‘ workplace: Diabetologické centrum Kliniky gerontologické a metabolické Lékařské fakulty UK a FN Hradec Králové, přednosta prof. MUDr. Luboš Sobotka, CSc.
Published in: Vnitř Lék 2011; 57(4): 391-395
Category: 12th national Symposium diabetes, "Diabetes and Gastroenterology", Hradec Kralove, 4 to 5 June 2010

Overview

Dyspeptic syndrome is a common complication of treatment with antidiabetic drugs. This may be a trivial as well as a very serious complication. Nauzea, vomiting, diarrhoea, abdominal pain, loss of appetite and taste disturbances are the most common symptoms of dyspeptic problems in patients treated with metformin. They rarely are a reason for treatment discontinuation. Dyspeptic syndrome is a common complication in patients treated with acarbose, this may be prevented by reduced intake of sucrose. Pneumatosis cystoides intestinalis is a rare complication in acarbose-treated patients. Antiobesity agent orlistat is frequently associated with dyspeptic symptoms, particularly if fat intake is not reduced. Treatment with drugs affecting the incretin system (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) is very rarely complicated by acute pancreatitis. Glucagon-like peptide-1 receptor agonists may cause dyspeptic symptoms (nausea, vomiting, diarrhoea) at the beginning of treatment. These complaints usually cease and the treatment usually does not need to be discontinued.

Key words:
metformin – acarbose – orlistat – incretin treatment – upper dyspeptic syndrome – lower dyspeptic syndrome – pancreatitis – pneumatosis cystoides intestinalis

Sources

1. Schernthaner G, Barnett AH, Betteridge DJ et al. Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis. Diabetologia 2010; 53: 1258–1269.

2. Nathan DM, Davidson MB, DeFronzo RA et al. American Diabetes Association. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care 2007; 30: 753–759.

3. Svačina Š. Postavení metforminu jako antidiabetika první olby. Vnitř Lék 2010; 56: 1225–1227.

4. eMC. SPC Glucobay 50 mg tablets. http://www.medicines.org.uk/emc/medicine/19972/SPC/Glucobay+50mg+tablets/.

5. Vogel Y, Buchner NJ, Szpakowski M et al. Pneumatosis cystoides intestinalis of the ascending colon related to acarbose treatment: a case report. J Med Case Reports 2009; 3: 9216.

6. Tsujimoto T, Shioyama E, Moriya K. Pneumatosis cystoides intestinalis following alpha-glucosidase inhibitor treatment: a case report and review of the literature. World J Gastroenterol 2008; 14: 6087–6092.

7. Torgerson JS, Hauptman J, Boldrin MN et al. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 2004; 27: 155–161.

8. Chanoine JP, Hampl S, Jensen C et al. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA 2005; 293: 2873–2883.

9. Šmahelová A. Nová farmaka v léčbě diabetu a s čím se může dnes praktický lékař setkat. In: Léčba diabetika v praxi V. Praha: JS Partner, s.r.o. 2009.

10. Kieffer TJ, Habener JF. The glucagon-like peptides. Endocr Rev 1999; 20: 876–913.

11. Flint A, Raben A, Astrup A et al. Gucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 1998; 101: 515–520.

12. Wettergren A, Schjoldager B, Mortensen PE et al. Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci 1993; 38: 665–673.

13. During MJ, Cao L, Zuzga DS et al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med 2003; 9: 1173–1179.

14. Klonoff DC, Buse JB, Nielsen LL et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 2008; 24: 275–286.

15. Gallwitz B. Exenatide in type 2 diabetes: treatment effects in clinical studies and animal study data. Int J Clin Pract 2006; 60: 1654–1661.

16. Barnett AH, Burger J, Johns D et al. Tolerability and efficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or a sulfonylurea: a multinational, randomized, open-label, two-period, crossover noninferiority trial. Clin Ther 2007; 29: 2333–2348.

17. 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, open-label trial (LEAD-6). Lancet 2009; 374: 39–47.

18. Garber A, Henry R, Ratner R et al. LEAD-3 (Mono) Study Group. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 2009; 373: 473–481.

19. Christensen M, Knop FK, Holst JJ et al. Lixisenatide, a novel GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus. IDrugs 2009; 12: 503–513.

20. Vilsbøll T, Zdravkovic M, Le-Thi T et al. Liraglutide, a long-acting human glucagon-like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care 2007; 30: 1608–1610

21. SPC Galvus 50 mg tablets. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000771/WC500020327.pdf.

22. Butler PC, Matveyenko AV, Dry S et al. Glucagon-like peptide-1 therapy and the exocrine pancreas: innocent bystander or friendly fire? Diabetologia 2010; 53: 1–6.

23. Noel RA, Braun DK, Patterson RE et al. Increased risk of acute pancreatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study. Diabetes Care 2009; 32: 834–838.

24. 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: 1019–1027.

25. Anderson SL, Trujillo JM. Association of pancreatitis with glucagon-like peptide-1 agonist use. Ann Pharmacother 2010; 44: 904–909.

26.http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm183764.htm

27. 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: 984–990.

28. Stoffers DA, Kieffer TJ, Hussain MA et al. Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas. Diabetes 2000; 49: 741–748.

29. Landi S. Genetic predisposition and environmental risk factors to pancreatic cancer: A review of the literature. Mutat Res 2009; 681: 299–307.

30. Jura N, Archer H, Bar-Sagi D. Chronic pancreatitis, pancreatic adenocarcinoma and the black box in-between. Cell Res 2005; 15: 72–77.

31. Butler PC, Matveyenko AV, Dry S et al. Glucagon-like peptide-1 therapy and the exocrine pancreas: innocent bystander or friendly fire? Diabetologia 2010; 53: 1–6.

32. Matveyenko AV, Dry S, Cox HI et al. Beneficial endocrine but adverse exocrine effect of Sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes, interactions with metformin. Diabetes 2009; 58: 1644–1645.