sulfonylurea
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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
- constipation, diarrhea, heartburn, anorexia, epigastric fullness
- dizziness
- 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]
- increased appetite, weight gain
- 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]
- increased risk for dementia vs metformin (12%)[9] or DPP4 inhibitor (RR=1.1)[13]
- increased risk for pancreatic cancer (RR=1.26)[12]
- toxicity:
- hypoglycemia:
- confusion, seizure, anxiety, diaphoresis
- dextrose + octreotide, glucagon temporizing
- monitor for 48 hours
- hypoglycemia:
Drug interactions
- drugs in combination that increase risk of hypoglycemia
- drug interaction(s) of sulfonylureas with warfarin
- drug interaction(s) of beta-adrenergic receptor antagonists with sulfonylureas
- drug interaction(s) of fluroquinolones with sulfonylureas
- drug interaction(s) of macrolides with sulfonylureas
- drug interaction(s) of salicylates with sulfonylureas
- drug interaction(s) of gliptins with sulfonylureas
- drug interaction(s) of fluoroquinolones with hypoglycemic agents
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]
- stimulation of insulin secretion in the absence of hyperglycemia inhibits hepatic & renal gluconeogenesis due to the presence of insulin
More general terms
More specific terms
- acetohexamide (Dymelor)
- chlorpropamide (Diabinese)
- glimepiride (Amaryl)
- glipizide (Glucotrol, Glucotrol XL)
- glyburide; glibenclamide (Micronase, DiaBeta, Glynase)
- tolazamide (Tolinase)
- tolbutamide (Orinase)
Additional terms
- 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)
References
- ↑ Lee A. UCLA Multicampus Program in Geriatrics & Gerontology, weekly lecture series, 2/14/02
- ↑ Jump up to: 2.0 2.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23128859 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23128866 <Internet> http://annals.org/article.aspx?articleid=1389852 - ↑ 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/1995959 <Internet> http://www.bmj.com/content/339/bmj.b4731
- ↑ Jump up to: 4.0 4.1 Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
- ↑ Jump up to: 5.0 5.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24915260 <Internet> http://www.jwatch.org/na34894/2014/06/10/insulin-or-sulfonylureas-supplement-metformin-patients
- ↑ Jump up to: 6.0 6.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27413017 Free full text <Internet> http://www.bmj.com/content/354/bmj.i3625
- ↑ Jump up to: 7.0 7.1 The Washington Manual of Medical Therapeutics, Cooper DH et al (eds) Lippincott, Williams & Wilkins, Philadelphia, 2007. pg 610
- ↑ Jump up to: 8.0 8.1 Medical Knowledge Self Assessment Program (MKSAP) 19 American College of Physicians, Philadelphia 2022
- ↑ Jump up to: 9.0 9.1 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: https://www.ncbi.nlm.nih.gov/pubmed/36220195 PMCID: PMC9472121 Free PMC article https://drc.bmj.com/content/10/5/e002894 - ↑ Jump up to: 10.0 10.1 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: https://www.ncbi.nlm.nih.gov/pubmed/36495141 https://agsjournals.onlinelibrary.wiley.com/doi/abs/10.1111/jgs.18160
- ↑ Jump up to: 11.0 11.1 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: https://www.ncbi.nlm.nih.gov/pubmed/36944118 PMCID: PMC10154665 Free PMC article https://diabetesjournals.org/care/article/46/5/967/148656/Cardiovascular-Safety-in-Type-2-Diabetes-With
- ↑ Jump up to: 12.0 12.1 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: https://www.ncbi.nlm.nih.gov/pubmed/37481610 PMCID: PMC10363143 Free PMC article https://rdcu.be/dh4Er
- ↑ Jump up to: 13.0 13.1 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: https://www.ncbi.nlm.nih.gov/pubmed/37218376 https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.18397
- ↑ Jump up to: 14.0 14.1 14.2 14.3 NEJM Knowledge+