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drug adverse effects of incretin mimetics

Adverse effects: - increased risk of pancreatitis? [1]; no [3,5] - probably no increased risk for pancreatitis [3,4] - increased risk of pancreatitis when used for weight loss [15] - increased risk for pancreatic duct metaplasia? [2]; no [3] - no increased risk of pancreatic cancer [5] - no increased risk for pancreatic disease [3] - delayed gastric emptying, gastroparesis* [14] - risk of residual gastric contents on day of elective surgery [19] - increased risk of gastroparesis when used for weight loss [15] - increased risk of bowel obstruction when used for weight loss [15] - not associated with increased risk for hospitalization due to heart failure [6] - cases of postmarketing acute cholecystitis with GLP-1 mimetics [12] - increased risk of gallbladder disease & disorder of the bile ducts [7] - may increase risk for cholangiocarcinoma [10] - increased risk of gallbladder or biliary diseases, especially when used at higher doses, for longer durations, & for weight loss [11] - no increased risk for breast cancer [8] - increased risk of overall thyroid cancer (RR=1.52) but not papillary thyroid cancer or medullary thyroid cancer [16] - no increased risk of mortality [9] - alopecia, pulmonary aspiration, suicidal ideation (potential) [17] - FDA clears GLP-1 receptor agonists of suicidal risk, but continues review [17] - pulmonary aspiration during general anesthesia or deep sedation [21] - no increased risk of suicide in patients without mental illness [20] - questions remain regarding use in patient with depression [20] * Black box warning of contraindication for personal of family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia-2 (MEN2) (based on rodent studies where GLP-1 receptors on parfollicular cells induced C-cell proliferation & develpment of C-sell tumors) [13] * prone to retained gastric contents on upper GI endoscopy [14] - 8-hour solid-food fast & 2-hour liquid fast prior to the procedure, - delay procedure if nausea, vomiting, or abdominal distension [18]

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DRUGS: GLP-1 receptor agonist FORM: drug adverse effects glp 1 receptor agonist

References

  1. Singh S 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;():1-6. PMID: 23440284 http://archinte.jamanetwork.com/article.aspx?articleid=1656537
  2. FDA Drug Safety Communication: FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes. http://www.fda.gov/Drugs/DrugSafety/ucm343187.htm
  3. Egan AG et al Pancreatic Safety of Incretin-Based Drugs - FDA and EMA Assessment. N Engl J Med 2014; 370:794-797February 27, 2014 PMID: 24571751 http://www.nejm.org/doi/full/10.1056/NEJMp1314078
  4. Li L 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 Apr 15; 348:g2366. PMID: 24736555 - Faillie JL et al. Incretin based drugs and risk of acute pancreatitis in patients with type 2 diabetes: Cohort study. BMJ 2014 Apr 24; 348:g2780 PMID: 24764569
  5. Azoulay L et al Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study. BMJ 2016;352:i581 PMID: 26888382 Free Article http://www.bmj.com/content/352/bmj.i581 - Bolen SD, Maruthur NM The safety of incretin based drug treatments for type 2 diabetes. BMJ 2016;352:i801 PMID: 26888024 http://www.bmj.com/content/352/bmj.i801
  6. Filion KB, Azoulay L, Platt RW et al A Multicenter Observational Study of Incretin-based Drugs and Heart Failure. N Engl J Med 2016; 374:1145-1154. March 24, 2016 PMID: 27007958 http://www.nejm.org/doi/full/10.1056/NEJMoa1506115
  7. Faillie JL, Yu OH, Yin H et al Association of Bile Duct and Gallbladder Diseases With the Use of Incretin-Based Drugs in Patients With Type 2 Diabetes Mellitus. JAMA Intern Med. Published online August 01, 2016 PMID: 27478902 http://archinte.jamanetwork.com/article.aspx?articleid=2540538 - Butler PC Glucagon-Like Peptide 1 Drugs as Second-Line Therapy for Type 2 Diabetes.' JAMA Intern Med. Published online August 01, 2016 PMID: 27479247 http://archinte.jamanetwork.com/article.aspx?articleid=2540531
  8. Hicks BM, Yin H, Yu OH et al Glucagon-like peptide-1 analogues and risk of breast cancer in women with type 2 diabetes: population based cohort study using the UK Clinical Practice Research Datalink. BMJ 2016;355:i5340 PMID: 27797785 Free Article http://www.bmj.com/content/355/bmj.i5340 - Bolen SD, Maruthur NM Glucagon-like peptide-1 receptor agonists and risk of breast cancer. BMJ 2016;355:i5519 PMID: 27797789 http://www.bmj.com/content/355/bmj.i5519
  9. Liu J, Li L, Deng K et al Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis. BMJ. 2017 Jun 8;357:j2499. Review. PMID: 28596247 Free PMC Article
  10. Abrahami D, Douros A, Yin H et al Incretin based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: population based cohort study. BMJ 2018;363:k4880 PMID: 30518618 https://www.bmj.com/content/363/bmj.k4880
  11. He L, Wanf J, Ping F et al Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases. A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Intern Med. Published online March 28, 2022 PMID: 35344001 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2790392 - Halder S, Lipska KJ Glucagon-Like Peptide-1 Receptor Agonists - How Safe Are They? JAMA Intern Med. Published online March 28, 2022 PMID: 35344015 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2790398
  12. Woronow D, Chamberlain C, Niak A et al Acute Cholecystitis Associated With the Use of Glucagon-Like Peptide-1 Receptor Agonists Reported to the US Food and Drug Administration. JAMA Intern Med. Published online August 29, 2022 PMID: 36036939 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2795476
  13. NEJM Knowledge+ Endocrinology
  14. Kobori T et al. Association of glucagon-like peptide-1 receptor agonist treatment with gastric residue in an esophagogastroduodenoscopy. J Diabetes Investig 2023 Jun; 14:767. PMID: 36919944 PMCID: PMC10204182 Free PMC article https://onlinelibrary.wiley.com/doi/10.1111/jdi.14005
  15. Sodhi M, Rezaeianzadeh R, Kezouh A et al Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. JAMA. Published online October 5, 2023 PMID: 37796527 https://jamanetwork.com/journals/jama/fullarticle/2810542
  16. Silverii GA, Monami M, Gallo M et al Glucagon-like peptide-1 receptor agonists and risk of thyroid cancer: A systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2023 Nov 29. PMID: 38018310
  17. O'Mary L FDA Evaluating Three Side Effects Reported With Weight Loss Drugs. Medscape. January 05, 2024 https://www.medscape.com/s/viewarticle/fda-investigates-three-side-effects-reported-weight-loss-2024a10000e4 - Monaco K FDA Clears Wegovy, Other GLP-1 Drugs of Suicidality Risk for Now. Preliminary evaluation reassures, while the agency's review continues. MedPage Today January 11, 2024 https://www.medpagetoday.com/primarycare/obesity/108223
  18. Hashash JG et al. AGA Rapid Clinical Practice Update on the management of patients taking GLP-1 receptor agonists prior to endoscopy: Communication. Clin Gastroenterol Hepatol 2024 Apr; 22:705 PMID: 37944573 https://www.cghjournal.org/article/S1542-3565(23)00869-8/fulltext
  19. Sen S et al. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surg 2024 Jun; 159:660. PMID: 38446466 PMCID: PMC10918573 (available on 2025-03-06) https://jamanetwork.com/journals/jamasurgery/fullarticle/2815663
  20. Ueda P, Soderling J, Wintzell V et al GLP-1 Receptor Agonist Use and Risk of Suicide Death. JAMA Intern Med. 2024 Sep 3:e244369. PMID: 39226030 PMCID: PMC11372654 Free PMC article. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2823083 - Wadden TA et al. Psychiatric safety of semaglutide for weight management in people without known major psychopathology: Post hoc analysis of the STEP 1, 2, 3, and 5 trials. JAMA Intern Med 2024 Sep 3; [e-pub] PMID: 39226070 PMCID: PMC11372653 Free PMC article. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2823084 - Schoretsanitis G et al. Disproportionality analysis from World Health Organization data on semaglutide, liraglutide, and suicidality. JAMA Netw Open 2024 Aug; 7:e2423385. PMID: 39163046 PMCID: PMC11337067 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2822453
  21. Larkin M FDA Updates GLP-1 Label With Pulmonary Aspiration Warning Medscape. Nov 6, 2024 https://www.medscape.com/viewarticle/fda-updates-glp-1-label-pulmonary-aspiration-warning-2024a1000k84