empagliflozin (Jardiance)
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Indications
- diabetes mellitus type 2 alone or in combination with other hypoglycemic agents
- may reduce cardiovascular risk in patients with type 2 diabetes
- reduces cardiovascular death (3.7% vs 5.9%), overall mortality (5.7% vs 8.3%) & hospitalization for heart failure (2.7% vs 4.1%) relative to placebo[4]
- benefits same at 10 mg & 25 mg doses[4]
- FDA approves use for cardiovascular risk reduction[6]
- in combination with metformin only if a sulfonylurea is not an option, or the person is at risk of hypoglycemia (NICE)
- may help slow progression of diabetic nephropathy in patients with type 2 diabetes at high cardiovascular risk[5]
- reduces progression of kidney disease & cardiovascular death independent of diabetes[24]
- benefit most pronounced in patients with significant albuminuria[25]
- lowers risk of cardiovascular death or hospitalization for heart failure among patients with systolic heart failure (HFrEF), regardless of diabetes status[8]
- benefit of empagliflozin for HFrEF regardless of dose of ACE inhibitor or ARB used in combination[14]
- improves functional capacity & quality of life after 6 months of treatment for systolic heart failure in patients without diabetes mellitus[9]
- effective for systolic heart failure with or without volume overload[10]
- reduces combined risk of cardiovascular death or hospitalization for heart failure in patients with HFpEF, regardless of diabetes status[12]
- modest improvement in health-related quality of life for patients with HFpEF[13]
- provides low economic value compared with standard of care for HFpEF, largely due to lack of efficacy on mortality & small benefit on quality of life[18]
- increases urine output 25% over 5 days in patients with acute heart failure without adverse renal effects; eGFR not affected[16]
- improves health-related quality of life at 90 days after acute heart failure[15]
- benefits begin at day 15
- reduces macro-albuminuria[19]
Contraindications
- diabetes mellitus type 1
- renal impairment: GFR < 30 ml/min/1.73 m2[16]
* among patients with eGFR of 20-45 mL/min, empaglifozin 10 mg QD decreased risk of progression of kidney disease or death from cardiovascular causes[17]
Dosage
- stop 3 days prior to surgery
* in patients with HFpEF, need for diuretics generally less in patients also using empagliflozin[20]
Adverse effects
- urinary tract infection
- genital infection (RR=3)[4]
- female genital infection, vaginal yeast infection[3]
- for a single episode of candidiasis in patient taking flozin, treat candidiasis & continue flozin[21][22]
- ketoacidosis[2]
- dehydration[3]
- necrotizing fasciitis, Fournier Gangrene of perineum (class effect)[23]
- drug adverse effects of hypoglycemic agents
- drug adverse effects of oral glucosuric agent; SGLT-2 inhibitor; flozin
Drug interactions
- little influence of aldosterone antagonists spironolactone or eplerenone on SGLT2-inhibitor empagliflozin benefits for patients with left ventricular systolic dysfunction[11]
- drug interaction(s) SGLT2 inhibitors (flozins) with diuretics
- drug interaction(s) of SGLT-2 inhititor (flozin) in combination with GLP1-agonist
- drug interaction(s) of aldosterone antagonists with SGLT2-inhibitor
- drug interaction(s) of fluoroquinolones with hypoglycemic agents
Mechanism of action
- inhibits sodium glucose cotransporter 2 (SGLT2)
- increases glucosuria
- may reduce intraglomerular pressure & hyperfiltration in patients with type 2 diabetes[5]
- can lower systolic blood pressure 4-8 mm Hg[22]
Notes
- efficacy of empagliflozin in reducing HbA1c in clinical trials translates into real-world effectiveness[7]
- empagliflozin more effective than dapagliflozin in reducing hospitalization or all-cause mortality[26] or compared with patients who started dapagliflozin
More general terms
Component of
References
- ↑ Medscape: August 1, 2014 Diabetes Drug Empagliflozin (Jardiance) Wins FDA OK on Second Try. http://www.medscape.com/viewarticle/829326
- ↑ Jump up to: 2.0 2.1 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
- ↑ Jump up to: 3.0 3.1 3.2 Lily News Release. Aug. 20, 2015 Jardiance<TM> demonstrated cardiovascular (CV) risk reduction in people with type 2 diabetes at high risk for CV events. https://investor.lilly.com/releasedetail.cfm?ReleaseID=928280
- ↑ Jump up to: 4.0 4.1 4.2 4.3 Zinman B et al Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. Sept 17, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26378978 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1504720
- ↑ Jump up to: 5.0 5.1 5.2 Wanner C et al Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. June 14, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27299675 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1515920
Ingelfinger JR, Rosen CJ Cardiac and Renovascular Complications in Type 2 Diabetes - Is There Hope? N Engl J Med. June 14, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26605932 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1607413 - ↑ Jump up to: 6.0 6.1 Gever J Jardiance Wins CV Prevention Indication. FDA approves claim that diabetes drug reduces cardiovascular death risk. Medpage Today. December 02, 2016 http://www.medpagetoday.com/Cardiology/Prevention/61822
Tucker ME FDA Approves Empagliflozin for Reducing CVD Death. Medscape. Dec 02, 2016. http://www.medscape.com/viewarticle/872697
FDA News Release. Dec 2, 2016 FDA approves Jardiance to reduce cardiovascular death in adults with type 2 diabetes. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm531517.htm - ↑ Jump up to: 7.0 7.1 Munk NE, Knudsen JS, Pottegard A, Witte DR, Thomsen RW. Differences Between Randomized Clinical Trial Participants and Real-World Empagliflozin Users and the Changes in Their Glycated Hemoglobin Levels. JAMA Netw Open. 2020;3(2):e1920949. Feb 7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32031651 Free Article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2760444
- ↑ Jump up to: 8.0 8.1 Phend C Second SGLT2 Drug Scores for HFrEF, Regardless of Diabetes Status.
EMPEROR-Reduced trial "exceptionally concordant" with DAPA-HF results. MedPage Today August 28, 2020 https://www.medpagetoday.com/meetingcoverage/esc/88346
Packer M, Anker S, Butler J et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020 Aug 29; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32865377 https://www.nejm.org/doi/10.1056/NEJMoa2022190 - ↑ Jump up to: 9.0 9.1 Santos-Gallego CG et al. Randomized trial of empagliflozin in nondiabetic patients with heart failure and reduced ejection fraction. J Am Coll Cardiol 2021 Jan 26; 77:243 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33197559. https://www.sciencedirect.com/science/article/abs/pii/S0735109720377536
Goldberg LR. The pleiotropic effects of SGLT2 inhibitors: Remodeling the treatment of heart failure. J Am Coll Cardiol 2021 Jan 26; 77:256. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33478648 https://www.sciencedirect.com/science/article/abs/pii/S0735109720378931 - ↑ Jump up to: 10.0 10.1 Packer M et al. Empagliflozin in patients with heart failure, reduced ejection fraction, and volume overload: EMPEROR-Reduced trial. J Am Coll Cardiol 2021 Mar 23; 77:1381. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33736819 https://www.sciencedirect.com/science/article/pii/S0735109721002023
Kosiborod M, Vaduganathan M. SGLT-2 inhibitors in heart failure: Volume or value? J Am Coll Cardiol 2021 Mar 23; 77:1393. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33736820 https://www.sciencedirect.com/science/article/abs/pii/S0735109721003090 - ↑ Jump up to: 11.0 11.1 Ferreira JP et al. Interplay of mineralocorticoid receptor antagonists and empagliflozin in heart failure: EMPEROR-Reduced. J Am Coll Cardiol 2021 Mar 23; 77:1397 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33736821 Free article https://www.sciencedirect.com/science/article/pii/S0735109721002394
- ↑ Jump up to: 12.0 12.1 Anker SD, Butler J, Filippatos G et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 2021. Oct 14;385(16):1451-1461. Aug 27; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/34449189 https://www.nejm.org/doi/10.1056/NEJMoa2107038
- ↑ Jump up to: 13.0 13.1 Butler J, Filippatos G, Siddiqi TJ et al Empagliflozin, health status, and quality of life in patients with heart failure and preserved ejection fraction: The EMPEROR-Preserved Trial. Circulation 2021 Nov 15; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34779658 Free article https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.057812
- ↑ Jump up to: 14.0 14.1 Verma S, Dhingra NK, Butler J et al. Empagliflozin in the treatment of heart failure with reduced ejection fraction in addition to background therapies and therapeutic combinations (EMPEROR-Reduced): A post-hoc analysis of a randomised, double-blind trial. Lancet Diabetes Endocrinol 2022 Jan; 10:35. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34861154 https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00292-8/fulltext
Ryden L, Ferrannini G. Is the impact of add on heart failure therapy influenced by background therapy? Lancet Diabetes Endocrinol 2022 Jan; 10:3 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34861151 https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00311-9/fulltext - ↑ Jump up to: 15.0 15.1 Kosiborod MN et al. Effects of empagliflozin on symptoms, physical limitations and quality of life in patients hospitalized for acute heart failure - Results from the EMPULSE trial. Circulation 2022 Apr 4; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/35377706 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.059725
- ↑ Jump up to: 16.0 16.1 16.2 Schulze PC et al. Effects of early empagliflozin initiation on diuresis and kidney function in patients with acute decompensated heart failure (EMPAG-HF). Circulation 2022 Jun 29; PMID: https://www.ncbi.nlm.nih.gov/pubmed/35766022 Free article https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.059038
- ↑ Jump up to: 17.0 17.1 The EMPA-KIDNEY Collaborative Group Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2022. Nov 4 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36331190 https://www.nejm.org/doi/full/10.1056/NEJMoa2204233
- ↑ Jump up to: 18.0 18.1 Zheng J, Parizo JT, Spertus JA et al Cost-effectiveness of Empagliflozin in Patients With Heart Failure With Preserved Ejection Fraction. JAMA Intern Med. Published online November 7, 2022 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36342696 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2797773
- ↑ Jump up to: 19.0 19.1 Ferreira JP, Zannad F, MD, Butler J et al Association of Empagliflozin Treatment With Albuminuria Levels in Patients With Heart Failure. A Secondary Analysis of EMPEROR-Pooled. JAMA Cardiol. 2022;7(11):1148-1159 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36129693 PMCID: PMC9494272 Free PMC article https://jamanetwork.com/journals/jamacardiology/fullarticle/2796744
- ↑ Jump up to: 20.0 20.1 Butler J, Shariq Usman M, Filippatos G et al Safety and Efficacy of Empagliflozin and Diuretic Use in Patients with Heart Failure and Preserved Ejection Fraction. A Post Hoc Analysis of the EMPEROR- Preserved Trial. JAMA Cardiol. Published online May 24, 2023. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37223933 https://jamanetwork.com/journals/jamacardiology/fullarticle/2805335
- ↑ Jump up to: 21.0 21.1 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.
- ↑ Jump up to: 22.0 22.1 22.2 NEJM Knowledge+ Endocrinology
- ↑ Jump up to: 23.0 23.1 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
- ↑ Jump up to: 24.0 24.1 EMPA-KIDNEY Collaborative Group Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial. Lancet Diabetes Endocrinol. 2024 Jan;12(1):51-60 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38061372 Free article https://www.thelancet.com/journals/landia/article/PIIS2213-8587(23)00322-4/fulltext
- ↑ Jump up to: 25.0 25.1 Alexander JT, Singh SK, Shah SD, Lambert B, Smith JP. 2023 Update in ambulatory general internal medicine Cleveland Clinic Journal of Medicine January 2024, 91 (1) 40-46 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38167397 Free article. Review. https://www.ccjm.org/content/91/1/40
- ↑ Jump up to: 26.0 26.1 Modzelewski KL, Pipilas A, Bosch NA Comparative Outcomes of Empagliflozin to Dapagliflozin in Patients With Heart Failure. JAMA Netw Open. 2024;7(5):e249305 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38696170 PMCID: PMC11066699 Free PMC article. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2818219
- ↑ Highlights of Prescribing Information JARDIANCE (empagliflozin tablets), for oral use https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Jardiance/jardiance.pdf