drug adverse effects of oral glucosuric agent; SGLT-2 inhibitor; flozin
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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
More general terms
References
- ↑ 1.0 1.1 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
- ↑ 2.0 2.1 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
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 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 - ↑ 4.0 4.1 4.2 Lowes R New FDA Watch List Flags More Drugs Medscape Internal Medicine. July 3, 2017 http://www.medscape.com/viewarticle/882425
- ↑ 5.0 5.1 Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/29677303 https://jamanetwork.com/journals/jama/fullarticle/2678616
- ↑ 7.0 7.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/30105365 - ↑ 8.0 8.1 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
- ↑ 9.0 9.1 9.2 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: https://www.ncbi.nlm.nih.gov/pubmed/30429124 https://www.bmj.com/content/363/bmj.k4365
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/30424892
Verma S, Juni P, Mazer CD. Pump, pipes, and filter: Do SGLT2 inhibitors cover it all? Lancet 2018 Nov 10; PMID: https://www.ncbi.nlm.nih.gov/pubmed/30424891 - ↑ 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/30497881 <Internet> http://www.onlinejacc.org/content/early/2018/11/23/j.jacc.2018.09.020
- ↑ 12.0 12.1 12.2 12.3 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: https://www.ncbi.nlm.nih.gov/pubmed/31060053 https://annals.org/aim/article-abstract/2732837/fournier-gangrene-associated-sodium-glucose-cotransporter-2-inhibitors-review-spontaneous
- ↑ 13.0 13.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/31357211 https://annals.org/aim/article-abstract/2739787/sodium-glucose-cotransporter-2-inhibitors-severe-urinary-tract-infections-reassuring - ↑ 14.0 14.1 14.2 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: https://www.ncbi.nlm.nih.gov/pubmed/32716707 https://www.acpjournals.org/doi/10.7326/M20-0289
- ↑ 15.0 15.1 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: https://www.ncbi.nlm.nih.gov/pubmed/32841351 https://www.medscape.com/viewarticle/938944
- ↑ 16.0 16.1 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: https://www.ncbi.nlm.nih.gov/pubmed/34705014 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2785536 - ↑ 17.0 17.1 Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
- ↑ 18.0 18.1 Schwartz B Fast Five Quiz: Penis Conditions and Disorders Medscape. Nov 29, 2022 https://reference.medscape.com/viewarticle/984322
- ↑ 19.0 19.1 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: https://www.ncbi.nlm.nih.gov/pubmed/36745425 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2800884
- ↑ 20.0 20.1 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: https://www.ncbi.nlm.nih.gov/pubmed/32808541 Review.
- ↑ 21.0 21.1 NEJM Knowledge+ Endocrinology
- ↑ 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