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drug adverse effects of oral glucosuric agent; SGLT-2 inhibitor; flozin

Adverse effects: - hypotension [3] - ketoacidosis (RR=2] [1,9,14]; class effect [14]; serum glucose may be normal [3] - euglycemic DKA - urinary tract infections [2] (candidiasis) [3] - no increased risk of severe urinary tract infections [13] - genital infections (vulvovaginal candidiasis) [3] - increased risk for balanitis & vulvovaginitis related to glucosuria [18] - for a single episode of candidiasis in patient taking flozin, treat candidiasis & continue flozin [20,21] - see vulvovaginal candidiasis for management - renal insufficiency - nocturia [17] - reports of nephrolithiasis* [4] - hypersensitivity reactions [3] - increased risk of foot amputations & toe amputations (RR=2.1) [9] osteomyelitis (RR=1.4); absolute risk low [7] - no increased risk of fractures in older adults with type 2 diabetes [16] - sepsis [12] - necrotizing fasciitis of the perineum, Fournier's gangrene (rare) [8,12] - 70% of victims are men [12] - increased risk of frailty - no evidence of dose-dependent overall safety observed in clinical usage of SGLT2 inhibitors [15] - no additional risk of adverse effects in patients with elevated HbA1c levels [19] * FDA decides no action necessary [4] Notes: - flozins on list of drugs to avoid - hypotension & urinary tract infections cited [5]

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DRUGS: SGLT-2 inhibitor FORM: drug adverse effects sglt 2 inhibitor

References

  1. FDA MedWatch. May 15, 2015 SGLT2 inhibitors: Drug Safety Communication - FDA Warns Medicines May Result in a Serious Condition of Too Much Acid in the Blood. https://mail.google.com/mail/u/0/?tab=wm#inbox/14d587f1089e0791
  2. FDA Safety Alert. Dec 4, 2015 SGLT2 Inhibitors: Drug Safety Communication - Labels to Include Warnings About Too Much Acid in the Blood and Serious Urinary Tract Infections. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm475553.htm
  3. Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015 - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Lowes R New FDA Watch List Flags More Drugs Medscape Internal Medicine. July 3, 2017 http://www.medscape.com/viewarticle/882425
  5. Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
  6. Zheng SL, Roddick AJ, Aghar-Jaffar R, et al Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes. A Systematic Review and Meta-analysis. JAMA. 2018;319(15):1580-1591. PMID: 29677303 https://jamanetwork.com/journals/jama/fullarticle/2678616
  7. Chang HY, Singh S, Mansour O, Baksh S, Alexander GC Association between sodium-glucose cotransporter 2 inhibitors and lower extremity amputation among patients with type 2 diabetes. JAMA Intern Med 2018 Aug 13; PMID: 30105373 - Fralick M, Patorno E, Fischer MA Sodium-glucose cotransporter 2 inhibitors and the risk of amputation: Results and challenges from the real world. JAMA Intern Med 2018 Aug 13; PMID: 30105365
  8. FDA Safety Alert. Ag 29, 2018 SGLT2(sodium-glucose cotransporter-2) Inhibitors for Diabetes: Drug Safety Communication - Regarding Rare Occurrences of a Serious Infection of the Genital Area. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm618908.htm
  9. Ueda P, Svanstrom H, Melbye M et al Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study. BMJ 2018;363:k4365 PMID: 30429124 https://www.bmj.com/content/363/bmj.k4365
  10. Zelniker TA, Wiviott SD, Raz I et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials. Lancet 2018 Nov 10; [e-pub]. (https://doi.org/10.1016/S0140-6736(18)32590-X) PMID: 30424892 - Verma S, Juni P, Mazer CD. Pump, pipes, and filter: Do SGLT2 inhibitors cover it all? Lancet 2018 Nov 10; PMID: 30424891
  11. Writing Committee, Das SR, Everett BM, Birtcher KK et al 2018 ACC Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease. A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. Nov 2018 PMID: 30497881 http://www.onlinejacc.org/content/early/2018/11/23/j.jacc.2018.09.020
  12. Bersoff-Matcha SJ, Chamberlain C, Cao C et al Fournier Gangrene Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Review of Spontaneous Postmarketing Cases. Ann Intern Med. 2019. May 7 PMID: 31060053 https://annals.org/aim/article-abstract/2732837/fournier-gangrene-associated-sodium-glucose-cotransporter-2-inhibitors-review-spontaneous
  13. Dave CV, Schneeweiss S, Kim D et al Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Severe Urinary Tract Infections: A Population-Based Cohort Study. Ann Intern Med. 2019. July 30 PMID: 31357213 https://annals.org/aim/article-abstract/2739786/sodium-glucose-cotransporter-2-inhibitors-risk-severe-urinary-tract-infections - Filion KB, Yu OH Sodium-Glucose Cotransporter-2 Inhibitors and Severe Urinary Tract Infections: Reassuring Real-World Evidence. Ann Intern Med. 2019. July 30 PMID: 31357211 https://annals.org/aim/article-abstract/2739787/sodium-glucose-cotransporter-2-inhibitors-severe-urinary-tract-infections-reassuring
  14. Douros A et al. Sodium-glucose cotransporter-2 inhibitors and the risk for diabetic ketoacidosis: A multicenter cohort study. Ann Intern Med 2020 Jul 28; PMID: 32716707 https://www.acpjournals.org/doi/10.7326/M20-0289
  15. Shi FH, Li H, Yue J et al Clinical Adverse Events of High-Dose vs Low-Dose Sodium-Glucose Cotransporter 2 Inhibitors in Type 2 Diabetes. A Meta-Analysis of 51 Randomized Clinical Trials. J Clin Endocrinol Metab. 2020;105(11) PMID: 32841351 https://www.medscape.com/viewarticle/938944
  16. Monaco K SGLT-2 Inhibitors Cleared of Bone Fracture Qualms in Older T2D Patients. New Medicare users of three classes of antidiabetic agents were compared. MedPage Today October 27, 2021 https://www.medpagetoday.com/endocrinology/diabetes/95290 - Zhuo M, Hawley CE, Paik JM et al Association of Sodium-Glucose Cotransporter-2 Inhibitors With Fracture Risk in Older Adults With Type 2 Diabetes. JAMA Netw Open. 2021;4(10):e2130762 PMID: 34705014 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2785536
  17. Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  18. Schwartz B Fast Five Quiz: Penis Conditions and Disorders Medscape. Nov 29, 2022 https://reference.medscape.com/viewarticle/984322
  19. D'Andrea E et al. Comparing effectiveness and safety of SGLT2 inhibitors vs DPP-4 inhibitors in patients with type 2 diabetes and varying baseline HbA1c levels. JAMA Intern Med 2023 Feb 6; [e-pub]. PMID: 36745425 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2800884
  20. Engelhardt K, Ferguson M, Rosselli JL. Prevention and Management of Genital Mycotic Infections in the Setting of Sodium-Glucose Cotransporter 2 Inhibitors. Ann Pharmacother. 2021 Apr;55(4):543-548. PMID: 32808541 Review.
  21. NEJM Knowledge+ Endocrinology
  22. Nishimura A et al Older Adults with Type 2 Diabetes: A Cross-Sectional Study. Drugs Aging. 2024. May 24 Not indexed in PubMed https://link.springer.com/article/10.1007/s40266-024-01119-8