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drug adverse effects of sulfonylureas

Adverse effects: 1) gastrointestinal a) common: (> 10%) - constipation, diarrhea, heartburn, anorexia, epigastric fullness b) uncommon (< 1%): cholestatic jaundice 2) dizziness (common) 3) hypoglycemia, especially with renal insufficiency [5] - among nursing home residents, new use of glimepiride & standard sulfonylurea dosing results in higher rates of severe hypoglycemia [8] - inhibition of gluconeogenesis by inappropriate stimulation of insulin secretion in the absence of hyperglycemia [11] - more important than masking symptoms of hypoglycemia by beta-blocker [11] - renal gluconeogenesis normally accounts for 20% of gluconeogenesis [11] 4) photosensitivity 5) increased appetite, weight gain [6] 6) bone marrow suppression (uncommon < 1%) - aplastic anemia, hemolytic anemia, thrombocytopenia, agranulocytosis 7) increased risk of cardiovascular & all-cause mortality [2] a) 1st & 2nd generation sulfonylureas are associated with higher mortality than metformin b) 2nd generation sulfonylureas are more likely to cause heart failure c) increased cardiovascular risk relative to metformin [3] d) compared with DPP-4 inhibitors & thiazolidinediones, sulfonylureas are not associated with increased risk for adverse cardiovascular events [9] 8) increased risk of dementia (12%) vs metformin [7] or DPP4 inhibitor (RR=1.1) [10] 9) toxicity: - hypoglycemia: - confusion, seizure, anxiety, diaphoresis - dextrose + octreotide, glucagon temporizing - monitor for 48 hours

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DRUGS: sulfonylurea FORM: drug adverse effects sulfonylurea

References

  1. Simpson SH, Majumdar SR, Tsuyuki RT, Eurich DT, Johnson JA. Dose-response relation between sulfonylurea drugs and mortality in type 2 diabetes mellitus: a population-based cohort study. CMAJ. 2006 Jan 17;174(2):169-74. PMID: 16415461 - Bell DS. Do sulfonylurea drugs increase the risk of cardiac events? CMAJ. 2006 Jan 17;174(2):185-6. No abstract available. PMID: 16415463 - Prescriber's Letter 13(3): 2006 Sulfonylureas and the Risk of Mortality Detail-Document#: 220307 (subscription needed) http://www.prescribersletter.com
  2. Tzoulaki I et al Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database BMJ 2009;339:b4731 PMID: 19959591 http://www.bmj.com/cgi/content/full/339/dec03_1/b4731
  3. Roumie CL et al Comparative Effectiveness of Sulfonylurea and Metformin Monotherapy on Cardiovascular Events in Type 2 Diabetes Mellitus: A Cohort Study Ann Intern Med. 6 November 2012;157(9):601-610 PMID: 23128859 http://annals.org/article.aspx?articleid=1389845 - Nissen SE Cardiovascular Effects of Diabetes Drugs: Emerging From the Dark Ages Ann Intern Med. 6 November 2012;157(9):671-672 PMID: 23128866 http://annals.org/article.aspx?articleid=1389852
  4. Jenkins-Jones S Association between first-line monotherapy with sulfonylurea versus metformin and risk of all-cause mortality. Abstract #201 http://www.easdvirtualmeeting.org/resources/3059
  5. van Dalem J et al Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group: population based cohort study. BMJ 2016;354:i3625 PMID: 27413017 Free full text http://www.bmj.com/content/354/bmj.i3625
  6. Medical Knowledge Self Assessment Program (MKSAP) 19 American College of Physicians, Philadelphia 2022
  7. Tucker ME One Type of Older Diabetes Drug Cuts Dementia Risk, Another Ups It. Medscape. Oct 11, 2022 https://www.medscape.com/viewarticle/982256 - Tang X et al Use of oral diabetes medications and the risk of incident dementia in US veterans aged >= 60 years with type 2 diabetes. BMJ Open Diabetes Research & Care. 2022 10(5): PMID: 36220195 PMCID: PMC9472121 Free PMC article https://drc.bmj.com/content/10/5/e002894
  8. Zullo AR Comparative safety of sulfonylureas among U.S. nursing home residents. J Am Geriatr Soc. 2023 Apr;71(4):1047-1057. Epub 2022 Dec 10. PMID: 36495141 https://agsjournals.onlinelibrary.wiley.com/doi/abs/10.1111/jgs.18160
  9. Wang H et al. Cardiovascular safety in type 2 diabetes with sulfonylureas as second-line drugs: A nationwide population-based comparative safety study. Diabetes Care 2023 Mar 21; 46:967. PMID: 36944118 PMCID: PMC10154665 Free PMC article https://diabetesjournals.org/care/article/46/5/967/148656/Cardiovascular-Safety-in-Type-2-Diabetes-With
  10. Wu CW, Iskander C, Wang C et al Association of sulfonylureas with the risk of dementia: A population-based cohort study. J Am Geriatr Soc. 2023. Oct;71(10):3059-3070 PMID: 37218376 https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.18397
  11. NEJM Knowledge+