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sulfonylurea

Indications: - treatment of diabetes mellitus type-2 - add-on treatment to metformin - may be safer than insulin* * insulin plus metformin associated with higher mortality than sulfonylurea plus metformin (mean age = 60 years; mean HgbA1c = 8.1%) [5] Monitor: - hemoglobin A1c every 6 months [7] Adverse effects: 1) constipation, diarrhea, heartburn, anorexia, epigastric fullness 2) dizziness 3) hypoglycemia, especially with renal insufficiency [6] - among nursing home residents, new use of glimepiride & standard sulfonylurea dosing results in higher rates of severe hypoglycemia [10] - inhibition of gluconeogenesis by inappropriate stimulation of insulin secretion in the absence of hyperglycemia [14] - more important than masking symptoms of hypoglycemia by beta-blocker [14] 4) increased appetite, weight gain 5) increased risk of adverse cardiovascular events [2] - 1st & 2nd generation sulfonylureas are associated with higher mortality than metformin - 2nd generation sulfonylureas are more likely to cause heart failure - compared with DPP-4 inhibitors & thiazolidinediones, sulfonylureas are not associated with increased risk for adverse cardiovascular events [11] 6) increased risk for dementia vs metformin (12%) [9] or DPP4 inhibitor (RR=1.1) [13] 7) increased risk for pancreatic cancer (RR=1.26) [12] 8) toxicity: - hypoglycemia: - confusion, seizure, anxiety, diaphoresis - dextrose + octreotide, glucagon temporizing - monitor for 48 hours Drug interactions: - drugs in combination that increase risk of hypoglycemia - macrolides: erythromycin, clarithromycin, azithromycin - fluoroquinolones: levofloxacin, ciprofloxacin - cephalexin [4] Mechanism of action: - stimulation of insulin secretion by closing the ATP-sensitive K+ channel of the beta-cell plasma membrane - stimulation of insulin secretion occurs regardless of glycemic status [8] - stimulation of insulin secretion in the absence of hyperglycemia inhibits hepatic & renal gluconeogenesis due to the presence of insulin - renal gluconeogenesis normally accounts for 20% of gluconeogenesis [14]

Interactions

drug interactions drug adverse effects (more general classes) monitor with sulfonylureas

Related

ATP-sensitive K+ channel (inwardly-rectifying K+ channel) incretin sulfonylurea receptor 1; ATP-binding cassette transporter sub-family C member 8; ATP-binding cassette C8 (ABCC8, HRINS, SUR SUR1)

Specific

acetohexamide (Dymelor) chlorpropamide (Diabinese) glimepiride (Amaryl) glipizide (Glucotrol, Glucotrol XL) glyburide; glibenclamide (Micronase, DiaBeta, Glynase) tolazamide (Tolinase) tolbutamide (Orinase)

General

oral hypoglycemic agent sulfa drug

Database Correlations

PUBCHEM cid=104818

References

  1. Lee A. UCLA Multicampus Program in Geriatrics & Gerontology, weekly lecture series, 2/14/02
  2. 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
  3. 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: 1995959 http://www.bmj.com/content/339/bmj.b4731
  4. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  5. Roumie CL et al. Association between intensification of metformin treatment with insulin vs sulfonylureas and cardiovascular events and all-cause mortality among patients with diabetes. JAMA 2014 Jun 11; 311:2288 PMID: 24915260 http://www.jwatch.org/na34894/2014/06/10/insulin-or-sulfonylureas-supplement-metformin-patients
  6. 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
  7. The Washington Manual of Medical Therapeutics, Cooper DH et al (eds) Lippincott, Williams & Wilkins, Philadelphia, 2007. pg 610
  8. Medical Knowledge Self Assessment Program (MKSAP) 19 American College of Physicians, Philadelphia 2022
  9. 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
  10. 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
  11. 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
  12. Chen Y et al Diabetes medications and cancer risk associations: a systematic review and meta-analysis of evidence over the past 10 years. Sci Rep. 2023 13(1):11844. July 22. PMID: 37481610 PMCID: PMC10363143 Free PMC article https://rdcu.be/dh4Er
  13. 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
  14. NEJM Knowledge+