dapagliflozin

Dapagliflozin is used along with diet, exercise, and usually with other glucose-lowering medications, to improve glycaemic control in adults with type{{nbsp}}2 diabetes. Dapagliflozin, in addition to other SGLT2-inhibitors, was shown to reduce the rate of decline in kidney function and kidney failure in non-diabetic and type{{nbsp}}2 diabetic adults when added to the existing treatment regimen.{{Cite journal | vauthors = ((The EMPA-KIDNEY Collaborative Group)) |date=2023-01-12 |title=Empagliflozin in Patients with Chronic Kidney Disease |journal=New England Journal of Medicine |volume=388 |issue=2 |pages=117–127 |doi=10.1056/NEJMoa2204233 |issn=0028-4793 |pmc=7614055 |pmid=36331190}}{{cite journal | vauthors = Heerspink HJ, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JF, McMurray JJ, Lindberg M, Rossing P, Sjöström CD, Toto RD, Langkilde AM, Wheeler DC | title = Dapagliflozin in Patients with Chronic Kidney Disease | journal = The New England Journal of Medicine | volume = 383 | issue = 15 | pages = 1436–1446 | date = October 2020 | pmid = 32970396 | doi = 10.1056/NEJMoa2024816 | s2cid = 221887260 | doi-access = free | title-link = doi | hdl = 2445/189959 | hdl-access = free }}{{cite journal | vauthors = Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJ, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW | title = Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy | journal = The New England Journal of Medicine | volume = 380 | issue = 24 | pages = 2295–2306 | date = June 2019 | pmid = 30990260 | doi = 10.1056/NEJMoa1811744 | hdl = 1805/22369 | s2cid = 117730201 | hdl-access = free }}{{cite journal | vauthors = Baigent C, Emberson J, Haynes R, Herrington WG, Judge P, Landray MJ, Mayne KJ, Ng SY, Preiss D, Roddick AJ, Staplin N, Zhu D, Anker SD, Bhatt DL, Brueckmann M | collaboration = Writing Committee, Smart-C Steering Committee | title = Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials | journal = Lancet | volume = 400 | issue = 10365 | pages = 1788–1801 | date = November 2022 | pmid = 36351458 | pmc = 7613836 | doi = 10.1016/S0140-6736(22)02074-8 }}

Guidelines including the European Society of Cardiology for Heart Failure and American Heart Association consider SGLT2-inhibitors such as Dapagliflozin as standard therapy for people with heart failure with reduced ejection fraction with a LVEF < 40%.{{cite journal | vauthors = McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JG, Coats AJ, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CS, Lyon AR, McMurray JJ, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GM, Ruschitzka F, Kathrine Skibelund A | title = 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure | journal = European Heart Journal | volume = 42 | issue = 36 | pages = 3599–3726 | date = September 2021 | pmid = 34447992 | doi = 10.1093/eurheartj/ehab368 }}{{cite journal | vauthors = Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW | title = 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines | journal = Journal of the American College of Cardiology | volume = 79 | issue = 17 | pages = 1757–1780 | date = May 2022 | pmid = 35379504 | doi = 10.1016/j.jacc.2021.12.011 }} This is supported by 2 large randomized controlled trials {{cite journal | vauthors = McMurray JJ, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CE, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM | title = Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction | journal = The New England Journal of Medicine | volume = 381 | issue = 21 | pages = 1995–2008 | date = November 2019 | pmid = 31535829 | doi = 10.1056/NEJMoa1911303 }}{{cite journal | vauthors = Nassif ME, Windsor SL, Tang F, Khariton Y, Husain M, Inzucchi SE, McGuire DK, Pitt B, Scirica BM, Austin B, Drazner MH, Fong MW, Givertz MM, Gordon RA, Jermyn R, Katz SD, Lamba S, Lanfear DE, LaRue SJ, Lindenfeld J, Malone M, Margulies K, Mentz RJ, Mutharasan RK, Pursley M, Umpierrez G, Kosiborod M | title = Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction: The DEFINE-HF Trial | journal = Circulation | volume = 140 | issue = 18 | pages = 1463–1476 | date = October 2019 | pmid = 31524498 | doi = 10.1161/CIRCULATIONAHA.119.042929 }} and a 2023 systematic review and meta-analysis.{{cite journal | vauthors = Ali AE, Mazroua MS, ElSaban M, Najam N, Kothari AS, Mansoor T, Amal T, Lee J, Kashyap R | title = Effect of Dapagliflozin in Patients with Heart Failure: A Systematic Review and Meta-Analysis | journal = Global Heart | volume = 18 | issue = 1 | pages = 45 | date = 2023-08-22 | pmid = 37636033 | pmc = 10453961 | doi = 10.5334/gh.1258 | doi-access = free }}

There is evidence from multiple studies that the addition of dapagliflozin and other medications from the SGLT2 inhibitor class to standard heart failure therapy can reduce the risk of worsening heart failure, hospitalisation for heart failure and cardiovascular death, regardless of the presence or absence of diabetes.{{Cite journal | vauthors = Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Silverman MG, Zelniker TA, Kuder JF, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JP, Ruff CT, Wiviott SD | title = Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes | journal = New England Journal of Medicine | volume = 380 | issue = 4 | pages = 347–357 | date = 2019-01-24 | pmid = 30415602 | doi = 10.1056/NEJMoa1812389 | url = https://www.nejm.org/doi/full/10.1056/NEJMoa1812389 | issn = 0028-4793 }}{{Cite journal | vauthors = Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, Boer RA, Desai AS, McMurray JJ | title = Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction | journal = New England Journal of Medicine | volume = 381 | issue = 21 | pages = 1995–2008 | date = 2019-11-21 | pmid = 31535829 | doi = 10.1056/NEJMoa1911303 | url = https://www.nejm.org/doi/full/10.1056/NEJMoa1911303 | issn = 0028-4793 }}{{Cite journal | vauthors = Windsor SL, Tang F, Khariton Y, Husain M, Inzucchi SE, McGuire DK, Pitt B, Scirica BM, Austin B, Drazner MH, Fong MW, Givertz MM, Gordon RA, Jermyn R, Nassif ME | title = Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction: The DEFINE-HF Trial | journal = Circulation | volume = 140 | issue = 18 | pages = 1463–1476 | date = 2019-10-29 | pmid = 31524498 | doi = 10.1161/CIRCULATIONAHA.119.042929 | url = https://pubmed.ncbi.nlm.nih.gov/31524498 | issn = 1524-4539 }}{{Cite journal | vauthors = Mazroua MS, ElSaban M, Najam N, Kothari AS, Mansoor T, Amal T, Lee J, Kashyap R, Ali AE | title = Effect of Dapagliflozin in Patients with Heart Failure: A Systematic Review and Meta-Analysis | journal = Global Heart | volume = 18 | issue = 1 | pages = 45 | date = 2023 | pmid = 37636033 | pmc = 10453961 | doi = 10.5334/gh.1258 | doi-access = free | issn = 2211-8179 }}{{Cite journal | vauthors = Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE, Zinman B | title = Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes | journal = New England Journal of Medicine | volume = 373 | issue = 22 | pages = 2117–2128 | date = 2015-11-26 | pmid = 26378978 | doi = 10.1056/NEJMoa1504720 | url = https://www.nejm.org/doi/full/10.1056/NEJMoa1504720 | issn = 0028-4793 }}{{Cite journal | vauthors = Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Packer M | title = Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure | journal = New England Journal of Medicine | volume = 383 | issue = 15 | pages = 1413–1424 | date = 2020-10-07 | pmid = 32865377 | doi = 10.1056/NEJMoa2022190 | url = https://www.nejm.org/doi/full/10.1056/NEJMoa2022190 | issn = 0028-4793 | hdl = 2066/230126 | hdl-access = free }} This benefit has been mostly studied in patients with heart failure with reduced ejection fraction (LVEF <40%) but there are emerging studies showing benefit in patients with heart failure with mildly reduced or preserved ejection fraction (LVEF >40%){{Cite journal | vauthors = McMurray JJ, Claggett B, Boer RA, DeMets D, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CS, Martinez F, Shah SJ, Desai AS, Jhund PS, Belohlavek J, Chiang CE, Solomon SD | title = Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction | journal = New England Journal of Medicine | volume = 387 | issue = 12 | pages = 1089–1098 | date = 2022-09-21 | pmid = 36027570 | doi = 10.1056/NEJMoa2206286 | url = https://www.nejm.org/doi/full/10.1056/NEJMoa2206286 | issn = 0028-4793 }}{{Cite journal | vauthors = Windsor SL, Borlaug BA, Kitzman DW, Shah SJ, Tang F, Khariton Y, Malik AO, Khumri T, Umpierrez G, Lamba S, Sharma K, Khan SS, Chandra L, Gordon RA, Nassif ME | title = The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial | journal = Nature Medicine | volume = 27 | issue = 11 | pages = 1954–1960 | date = November 2021 | pmid = 34711976 | doi = 10.1038/s41591-021-01536-x | pmc = 8604725 | language = en | issn = 1546-170X }} and there may also be some benefit for its use in acute heart failure as part of diuresis.{{Cite journal | vauthors = Collins SP, Hernandez GA, McRae AT, Davidson BT, Adams K, Aaron M, Cunningham L, Jenkins CA, Lindsell CJ, Harrell FE, Kampe C, Miller KF, Stubblefield WB, Lindenfeld J, Cox ZL | title = Efficacy and Safety of Dapagliflozin in Patients With Acute Heart Failure | journal = Journal of the American College of Cardiology | volume = 83 | issue = 14 | pages = 1295–1306 | date = 2024-04-09 | pmid = 38569758 | doi = 10.1016/j.jacc.2024.02.009 | url = https://pubmed.ncbi.nlm.nih.gov/38569758 | issn = 1558-3597 }} SGLT-2 inhibitors reduce the risk of hospitalisation due to heart failure in people with or without atherosclerotic cardiovascular disease {{cite journal |vauthors=McGuire DK, Shih WJ, Cosentino F, Charbonnel B, Cherney DZ, Dagogo-Jack S, Pratley R, Greenberg M, Wang S, Huyck S, Gantz I, Terra SG, Masiukiewicz U, Cannon CP |date=February 2021 |title=Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: A Meta-analysis |journal=JAMA Cardiology |volume=6 |issue=2 |pages=148–158 |doi=10.1001/jamacardio.2020.4511 |pmc=7542529 |pmid=33031522}}{{cite journal | vauthors = Bhattarai M, Salih M, Regmi M, Al-Akchar M, Deshpande R, Niaz Z, Kulkarni A, Siddique M, Hegde S | title = Association of Sodium-Glucose Cotransporter 2 Inhibitors With Cardiovascular Outcomes in Patients With Type 2 Diabetes and Other Risk Factors for Cardiovascular Disease: A Meta-analysis | journal = JAMA Network Open | volume = 5 | issue = 1 | pages = e2142078 | date = January 2022 | pmid = 34985519 | pmc = 8733833 | doi = 10.1001/jamanetworkopen.2021.42078 }}. Some meta-analyses and cohort studies suggest that dapagliflozin may provide advantages compared to other SGLT2 inhibitors like empagliflozin in specific heart failure hospitalisation, but the results can vary, and further comparative studies are required to establish consistent superiority.{{cite journal | vauthors = McMurray JJ, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CE, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM | title = Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction | journal = The New England Journal of Medicine | volume = 381 | issue = 21 | pages = 1995–2008 | date = November 2019 | pmid = 31535829 | doi = 10.1056/NEJMoa1911303 }}{{cite journal | vauthors = Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F | title = Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure | journal = The New England Journal of Medicine | volume = 383 | issue = 15 | pages = 1413–1424 | date = October 2020 | pmid = 32865377 | doi = 10.1056/NEJMoa2022190 | hdl = 2066/230126 | hdl-access = free }}{{cite journal | vauthors = Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, Brueckmann M, Ofstad AP, Pfarr E, Jamal W, Packer M | title = SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials | language = English | journal = Lancet | volume = 396 | issue = 10254 | pages = 819–829 | date = September 2020 | pmid = 32877652 | doi = 10.1016/S0140-6736(20)31824-9 }}

In the European Union, dapagliflozin is indicated in adults:{{cite web | title=Forxiga PI | website=Union Register of medicinal products | date=14 November 2012 | url=https://ec.europa.eu/health/documents/community-register/html/h795.htm | access-date=30 November 2024}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

• for the treatment of insufficiently controlled type{{nbsp}}2 diabetes as an adjunct to diet and exercise:{{cite journal | vauthors = Cefalu WT, Leiter LA, de Bruin TW, Gause-Nilsson I, Sugg J, Parikh SJ | title = Dapagliflozin's Effects on Glycemia and Cardiovascular Risk Factors in High-Risk Patients With Type 2 Diabetes: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With a 28-Week Extension | journal = Diabetes Care | volume = 38 | issue = 7 | pages = 1218–1227 | date = July 2015 | pmid = 25852208 | pmc = 4831907 | doi = 10.2337/dc14-0315 }}{{cite journal | vauthors = Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF | title = Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial | journal = Diabetes Care | volume = 33 | issue = 10 | pages = 2217–2224 | date = October 2010 | pmid = 20566676 | pmc = 2945163 | doi = 10.2337/dc10-0612 }}{{cite journal | vauthors = Rossing P, Inzucchi SE, Vart P, Jongs N, Docherty KF, Jhund PS, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Solomon SD, DeMets DL, Bengtsson O, Lindberg M, Langkilde AM, Sjöstrand M, Stefansson BV, Karlsson C, Chertow GM, Hou FF, Correa-Rotter R, Toto RD, Wheeler DC, McMurray JJ, Heerspink HJ | title = Dapagliflozin and new-onset type 2 diabetes in patients with chronic kidney disease or heart failure: pooled analysis of the DAPA-CKD and DAPA-HF trials | journal = The Lancet. Diabetes & Endocrinology | volume = 10 | issue = 1 | pages = 24–34 | date = January 2022 | pmid = 34856173 | doi = 10.1016/S2213-8587(21)00295-3 | s2cid = 244737266 | url = https://eprints.gla.ac.uk/261109/3/261109Suppl%28Figure%201%29.pdf }}
• as monotherapy when metformin is considered inappropriate due to intolerance;
• in addition to other medicinal products for the treatment of type{{nbsp}}2 diabetes;
• for the treatment of symptomatic chronic heart failure;
• for the treatment of chronic kidney disease

In November 2021, the European Medicines Agency (EMA) stated that dapagliflozin should no longer be used to treat type{{nbsp}}1 diabetes.

In 2021, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) expanded the indications for dapagliflozin to include the treatment of people who have chronic kidney disease but do not have diabetes.{{cite press release | title=FDA Approves Treatment for Chronic Kidney Disease | publisher=U.S. Food and Drug Administration (FDA) | date=30 April 2021 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-chronic-kidney-disease | access-date=30 April 2021 | archive-date=30 April 2021 | archive-url=https://web.archive.org/web/20210430203432/http://www.fda.gov/news-events/press-announcements/fda-approves-treatment-chronic-kidney-disease | url-status=dead }} {{PD-notice}}{{cite web | title=Forxiga EPAR | date=7 December 2012 | publisher=European Medicines Agency (EMA) | url=https://www.ema.europa.eu/en/medicines/human/EPAR/forxiga | access-date=17 February 2020 | archive-date=17 February 2020 | archive-url=https://web.archive.org/web/20200217204844/https://www.ema.europa.eu/en/medicines/human/EPAR/forxiga | url-status=live }} {{Include-FreeToUse|agency=European Medicines Agency|materialtype=copyrighted text that may be reproduced and/or distributed for non-commercial and commercial purposes, provided that the Agency is always acknowledged as the source of the material,|policy=https://www.ema.europa.eu/en/about-us/about-website/legal-notice|access-date=29 November 2024}}

Clinical trials have shown the following effects of such a treatment.

The DIAMOND trial (2017–2019) showed in treatment periods of six weeks no improvement of excess proteins in the urine (proteinuria), a significant deterioration of the kidney's filtration rate (reversible within 6 weeks after dapagliflozin discontinuation), and a significant mean loss of body weight of 1.5 kg.{{cite journal | vauthors = Cherney DZ, Dekkers CC, Barbour SJ, Cattran D, Abdul Gafor AH, Greasley PJ, Laverman GD, Lim SK, Di Tanna GL, Reich HN, Vervloet MG, Wong MG, Gansevoort RT, Heerspink HJ | title = Effects of the SGLT2 inhibitor dapagliflozin on proteinuria in non-diabetic patients with chronic kidney disease (DIAMOND): a randomised, double-blind, crossover trial | journal = The Lancet. Diabetes & Endocrinology | volume = 8 | issue = 7 | pages = 582–593 | date = July 2020 | pmid = 32559474 | pmc = | doi = 10.1016/S2213-8587(20)30162-5 | s2cid = 219948034 | url = https://pure.rug.nl/ws/files/147208221/Effects_of_the_SGLT2_inhibitor_dapagliflozin_on_proteinuria_in_non_diabetic_patients_with_chronic_kidney_disease_DIAMOND_a_randomised_double_blind_crossover_trial.pdf }}{{cite journal | vauthors = Yau K, Dharia A, Alrowiyti I, Cherney DZ | title = Prescribing SGLT2 Inhibitors in Patients With CKD: Expanding Indications and Practical Considerations | journal = Kidney International Reports | volume = 7 | issue = 7 | pages = 1463–1476 | date = July 2022 | pmid = 35812300 | pmc = 9263228 | doi = 10.1016/j.ekir.2022.04.094 }}

The DAPA-CKD trial (2017–2020) showed in a median treatment period of 2.4 years of participants who had already been under ACE inhibitor (ACE) or angiotensin II receptor blocker (ARB) therapy that the events of a sustained decline of 50% in the kidney's filtration rate, kidney failure, or death occurred statistically around eight months later in the treatment group than in the placebo group. In the first 12–16 months of treatment, however, the kidney filtration rate was worse in the treatment group than in the placebo group, being slightly less negative in the treatment group than in the placebo group only thereafter.

Since dapagliflozin leads to heavy glycosuria (sometimes up to about 70 grams per day), it can lead to rapid weight loss and tiredness. The glucose acts as an osmotic diuretic (this effect is the cause of polyuria in diabetes), which can lead to dehydration. The increased amount of glucose in the urine can also worsen the infections already associated with diabetes, particularly urinary tract infections and thrush (candidiasis). Rarely, the use of an SGLT-2 inhibitor medication, including dapagliflozin, is associated with necrotizing fasciitis of the perineum, also called Fournier gangrene.{{cite web|url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-rare-occurrences-serious-infection-genital-area-sglt2-inhibitors-diabetes|title=FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes|date=9 February 2019|publisher=U.S. Food and Drug Administration (FDA)|access-date=16 December 2019|archive-date=13 December 2019|archive-url=https://web.archive.org/web/20191213201737/https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-rare-occurrences-serious-infection-genital-area-sglt2-inhibitors-diabetes|url-status=dead}} {{PD-notice}}

Dapagliflozin is also associated with hypotensive reactions. Concerns exist that it may increase the risk of diabetic ketoacidosis.{{cite web | title = SGLT2 inhibitors: Drug Safety Communication - FDA Warns Medicines May Result in a Serious Condition of Too Much Acid in the Blood | url = https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm446994.htm | publisher = U.S. Food and Drug Administration (FDA) | access-date = 15 November 2016 | date = 15 May 2015 | archive-url=https://web.archive.org/web/20161027185104/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm446994.htm | archive-date=27 October 2016 | url-status=dead }} {{PD-notice}} Dapagliflozin and other SGLT2 inhibitors increase the risk of diabetic ketoacidosis in type{{nbsp}}2 diabetic patients.{{Cite journal |date=2019-05-09 |title=Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes |journal=New England Journal of Medicine |volume=380 |issue=19 |pages=1880–1882 |doi=10.1056/NEJMc1902837 |issn=0028-4793}}{{cite journal | vauthors = Liu J, Li L, Li S, Wang Y, Qin X, Deng K, Liu Y, Zou K, Sun X | title = Sodium-glucose co-transporter-2 inhibitors and the risk of diabetic ketoacidosis in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials | journal = Diabetes, Obesity & Metabolism | volume = 22 | issue = 9 | pages = 1619–1627 | date = September 2020 | pmid = 32364674 | doi = 10.1111/dom.14075 }} However, the DEPICT-1 and DEPICT-2 trials showed that dapagliflozin caused additional diabetic ketoacidosis events in the Type I diabetic patients who received dapagliflozin.{{cite journal | vauthors = Phillip M, Mathieu C, Lind M, Araki E, di Bartolo P, Bergenstal R, Heller S, Hansen L, Scheerer MF, Thoren F, Arya N, Xu J, Iqbal N, Dandona P | title = Long-term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: pooled 52-week outcomes from the DEPICT-1 and -2 studies | journal = Diabetes, Obesity & Metabolism | volume = 23 | issue = 2 | pages = 549–560 | date = February 2021 | pmid = 33145944 | pmc = 7839492 | doi = 10.1111/dom.14248 }} Symptoms of ketoacidosis include nausea, vomiting, abdominal pain, fatigue, and trouble breathing.

Dapagliflozin can cause dehydration, serious urinary tract infections, and genital yeast infections. Elderly people and people with kidney dysfunction, low blood pressure, or who are on diuretic medications should have their volume status and kidney function assessed. Individuals with signs and symptoms of metabolic acidosis or ketoacidosis should also be assessed. Dapagliflozin can cause low blood sugar when combined with insulin.

To lessen the risk of developing ketoacidosis after surgery, the US Food and Drug Administration (FDA) approved changes to the prescribing information for SGLT-2 inhibitors to recommend they be stopped temporarily before scheduled surgery. Canagliflozin, dapagliflozin, and empagliflozin should each be stopped at least three days before, and ertugliflozin should be stopped at least four days before scheduled surgery.{{cite web | title=FDA revises labels of SGLT2 inhibitors for diabetes to include warning | website=U.S. Food and Drug Administration | date=19 March 2020 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-revises-labels-sglt2-inhibitors-diabetes-include-warnings-about-too-much-acid-blood-and-serious | access-date=6 June 2020 | archive-date=7 June 2020 | archive-url=https://web.archive.org/web/20200607011955/https://www.fda.gov/drugs/drug-safety-and-availability/fda-revises-labels-sglt2-inhibitors-diabetes-include-warnings-about-too-much-acid-blood-and-serious | url-status=dead }} {{PD-notice}}

The glucose-lowering effect of dapagliflozin starts to diminish in people with chronic kidney disease with reduced kidney function (eGFR <45mL/min), and may not be as effective for glycemic control. However, studies have demonstrated a renoprotective effect in reducing kidney function decline, dapagliflozin can still be used to reduce kidney function decline regardless of diabetes status. Therefore, while dapagliflozin can be used in people with diabetes and chronic kidney disease to prevent kidney function decline, further interventions may be needed for glycemic control.{{cite journal | vauthors = Kohan DE, Fioretto P, Tang W, List JF | title = Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control | journal = Kidney International | volume = 85 | issue = 4 | pages = 962–971 | date = April 2014 | pmid = 24067431 | pmc = 3973038 | doi = 10.1038/ki.2013.356 }}

The first synthesis of dapagliflozin was disclosed in a patent filed by Bristol Myers Squibb in 2002.{{cite patent |country=US |number=6515117 |status=patent |pubdate=2003-02-04 |fdate=2002-05-20 |pridate=1999-10-12 |inventor=Ellsworth B, Washburn WN, Sher PM, Wu G, Meng W |title=C-aryl glucoside SGLT2 inhibitors and method |assign1=AstraZeneca }}

File:Dapaglifloxin synthesis.svg

The two main carbon-containing fragments are combined by the reaction of an aryl lithium with a trimethylsilyl-protected gluconolactone. The trimethylsilyl groups are then removed by treatment with methanesulfonic acid in methanol. This gives an intermediate with an unwanted methoxy group at the anomeric centre, which is removed by reaction with triethylsilane in the presence of boron trifluoride etherate. This route, as well as others developed for the manufacture of the drug, have been reviewed.{{cite journal |doi=10.1016/j.tet.2021.132378 |title=An overview of the synthetic routes to essential oral anti-diabetes drugs |year=2021 | vauthors = Sagandira CR, Khasipo AZ, Sagandira MB, Watts P |journal=Tetrahedron |volume=96 |page=132378 }}

Dapagliflozin inhibits subtype{{nbsp}}2 of the sodium-glucose transport proteins (SGLT2), which are responsible for at least 90% of the glucose reabsorption in the kidney. Blocking this transporter mechanism causes blood glucose to be eliminated through the urine.{{cite web|url=http://www.prous.com/molecules/default.asp?ID=165|archive-url=https://web.archive.org/web/20071105072914/http://www.prous.com/molecules/default.asp?ID=165|url-status=dead|archive-date=5 November 2007|title=Molecule of the Month: Clarivate| work = Prous Science | date = November 2007 }} In combination with metformin, dapagliflozin at standard treatment dose of 10 mg daily lowered HbA1c by 0.54-0.84% (5.9-9.3 mmol/mol) when compared to metformin monotherapy in patients with inadequately controlled type{{nbsp}}2 diabetes and normal renal function.{{cite journal | vauthors = Bailey CJ, Gross JL, Pieters A, Bastien A, List JF | title = Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial | journal = Lancet | volume = 375 | issue = 9733 | pages = 2223–2233 | date = June 2010 | pmid = 20609968 | doi = 10.1016/S0140-6736(10)60407-2 | s2cid = 9168659 }}{{cite journal | vauthors = Bailey CJ, Gross JL, Hennicken D, Iqbal N, Mansfield TA, List JF | title = Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial | journal = BMC Medicine | volume = 11 | issue = 1 | pages = 43 | date = February 2013 | pmid = 23425012 | pmc = 3606470 | doi = 10.1186/1741-7015-11-43 | s2cid = 16429125 | doi-access = free }}{{cite journal | vauthors = Henry RR, Murray AV, Marmolejo MH, Hennicken D, Ptaszynska A, List JF | title = Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial | journal = International Journal of Clinical Practice | volume = 66 | issue = 5 | pages = 446–456 | date = May 2012 | pmid = 22413962 | doi = 10.1111/j.1742-1241.2012.02911.x | s2cid = 9934488 | doi-access = free | title-link = doi }}

Its protective effects in heart failure are attributed primarily to haemodynamic effects, where SGLT2 inhibitors potently reduce intravascular volume through osmotic diuresis and natriuresis. This consequently may lead to a reduction in preload and afterload, thereby alleviating cardiac workload and improving left ventricular function.{{cite journal | vauthors = Lan NS, Fegan PG, Yeap BB, Dwivedi G | title = The effects of sodium-glucose cotransporter 2 inhibitors on left ventricular function: current evidence and future directions | journal = ESC Heart Failure | volume = 6 | issue = 5 | pages = 927–935 | date = October 2019 | pmid = 31400090 | pmc = 6816235 | doi = 10.1002/ehf2.12505 }}

The IC₅₀ for SGLT2 is less than one-thousandth of the IC₅₀ for SGLT1 (1.1 versus 1390 nmol/L), so that the drug does not interfere with intestinal glucose absorption.{{cite journal | vauthors = Schubert-Zsilavecz M, Wurglics M | title = Dapagliflozin | journal = Neue Arzneimittel | date = 2008–2009 }}

Dapagliflozin is the International nonproprietary name (INN),{{cite web | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 59 | url = https://www.who.int/medicines/publications/druginformation/innlists/RL59.pdf | publisher = World Health Organization | access-date = 15 November 2016 | page = 50 | date = 2008 | archive-date = 18 May 2016 | archive-url = https://web.archive.org/web/20160518193003/http://www.who.int/medicines/publications/druginformation/innlists/RL59.pdf | url-status = live }} and the United States Adopted Name (USAN).{{cite web|title=Statement on a Nonproprietary Name Adopted by the USAN Council |url=http://www.ama-assn.org/ama1/pub/upload/mm/365/dapagliflozin.pdf |publisher=American Medical Association |access-date=15 November 2016 |archive-url=https://web.archive.org/web/20120207124414/http://www.ama-assn.org/ama1/pub/upload/mm/365/dapagliflozin.pdf |archive-date=7 February 2012 |url-status=dead }}

The fixed-dose combination product, dapagliflozin/metformin extended-release, is sold under the brand name Xigduo XR.{{cite web | title = US FDA Approves Once-Daily Xigduo XR Tablets for Adults with Type 2 Diabetes | url = https://www.astrazeneca.com/media-centre/press-releases/2014/us-fda-approved-xigduo-type-2-diabetes-patients-30102014.html | publisher = AstraZeneca | date = 30 October 2014 | access-date = 15 November 2016 | archive-date = 16 November 2016 | archive-url = https://web.archive.org/web/20161116015521/https://www.astrazeneca.com/media-centre/press-releases/2014/us-fda-approved-xigduo-type-2-diabetes-patients-30102014.html | url-status = live }}{{cite web | title=Drug Approval Package: Xigduo XR (dapagliflozin and metformin HCl) Extended-Release Tablets | website=U.S. Food and Drug Administration (FDA) | date=7 April 2015 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205649Orig1s000TOC.cfm | access-date=5 May 2020 | archive-date=20 February 2020 | archive-url=https://web.archive.org/web/20200220075559/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205649Orig1s000TOC.cfm | url-status=live }}{{cite web | title=Xigduo XR- dapagliflozin and metformin hydrochloride tablet, film-coated, extended-release | website=DailyMed | date=3 February 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ac8a0f7b-9f69-4495-abbc-3a47cd75a859 | access-date=5 May 2020 | archive-date=2 March 2021 | archive-url=https://web.archive.org/web/20210302075051/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ac8a0f7b-9f69-4495-abbc-3a47cd75a859 | url-status=live }}

In July 2016, the fixed-dose combination of saxagliptin and dapagliflozin was authorized for medical use in the European Union and is sold under the brand name Qtern.{{cite web | title=Qtern EPAR | website=European Medicines Agency (EMA) | date=27 July 2016 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/qtern | access-date=7 May 2020 | archive-date=14 July 2020 | archive-url=https://web.archive.org/web/20200714202658/https://www.ema.europa.eu/en/medicines/human/EPAR/qtern | url-status=live }} The combination drug was approved for medical use in the United States in February 2017, where it also is sold under the brand name Qtern.{{cite web | title=Drug Approval Package: Qtern (dapagliflozin and saxagliptin) | website=U.S. Food and Drug Administration (FDA) | date=10 October 2018 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209091Orig1s000TOC.cfm | access-date=8 May 2020 | archive-date=14 July 2020 | archive-url=https://web.archive.org/web/20200714202646/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209091Orig1s000TOC.cfm | url-status=dead }}{{cite web | title=Qtern- dapagliflozin and saxagliptin tablet, film coated | website=DailyMed | date=24 January 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=423c489c-085b-4320-b892-7868ebd6dc6b | access-date=17 February 2020 | archive-date=14 July 2020 | archive-url=https://web.archive.org/web/20200714202647/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=423c489c-085b-4320-b892-7868ebd6dc6b | url-status=live }}

In May 2019, the fixed-dose combination of dapagliflozin, saxagliptin, and metformin hydrochloride as extended-release tablets was approved in the United States to improve glycemic control in adults with type{{nbsp}}2 diabetes when used in combination with diet and exercise. The FDA granted the approval of Qternmet XR to AstraZeneca.{{cite web | title=Drug Approval Package: Qternmet XR | website=U.S. Food and Drug Administration (FDA) | date=27 January 2020 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/210874Orig1s000TOC.cfm | access-date=17 February 2020 | archive-date=17 February 2020 | archive-url=https://web.archive.org/web/20200217083231/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/210874Orig1s000TOC.cfm | url-status=dead }} The combination drug was authorized for use in the European Union in November 2019, and is sold under the brand name Qtrilmet.{{cite web | title=Qtrilmet EPAR | website=European Medicines Agency (EMA) | date=16 September 2019 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/qtrilmet | access-date=30 March 2020 | archive-date=29 December 2019 | archive-url=https://web.archive.org/web/20191229223247/https://www.ema.europa.eu/en/medicines/human/EPAR/qtrilmet | url-status=live }}

In 2012, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion on the drug.{{cite web | title=Forxiga EPAR | website=European Medicines Agency (EMA) | date=7 December 2012 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/forxiga | access-date=17 February 2020 | archive-date=17 February 2020 | archive-url=https://web.archive.org/web/20200217204844/https://www.ema.europa.eu/en/medicines/human/EPAR/forxiga | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

Dapagliflozin was found effective in several studies in participants with type{{nbsp}}2 diabetes. The main measure of effectiveness was the level of glycated haemoglobin (HbA_1c), which indicates how well blood glucose is controlled.

In two studies involving 840 participants with type{{nbsp}}2 diabetes, dapagliflozin when used alone decreased HbA_1c levels by 0.66% more than placebo (a dummy treatment) after 24 weeks. In four other studies involving 2,370 participants, adding dapagliflozin to other diabetes medicines decreased HbA_1c levels by 0.54–0.68% more than adding placebo after 24 weeks.

In a study involving 814 participants with type{{nbsp}}2 diabetes, dapagliflozin used in combination with metformin was at least as effective as a sulphonylurea (another type of diabetes medicine) used with metformin. Both combinations reduced HbA_1c levels by 0.52% after 52 weeks.

A long-term study, involving over 17,000 participants with type{{nbsp}}2 diabetes, looked at the effects of dapagliflozin on cardiovascular (heart and circulation) disease. The study indicated that dapagliflozin's effects were in line with those of other diabetes medicines that also work by blocking SGLT2.

In two studies involving 1,648 participants with type{{nbsp}}1 diabetes whose blood sugar was not controlled well enough on insulin alone, adding dapagliflozin 5 mg decreased HbA_1c levels after 24 hours by 0.37% and by 0.42% more than adding placebo.

Dapagliflozin was authorized for medical use in the European Union in November 2012. It is sold in a number of European countries.{{cite web | title=Forxiga | website=Drugs.com | date=4 May 2020 | url=https://www.drugs.com/international/forxiga.html | access-date=5 May 2020 | archive-date=28 August 2021 | archive-url=https://web.archive.org/web/20210828053554/https://www.drugs.com/international/forxiga.html | url-status=live }}

Dapagliflozin was approved for medical use in the United States in January 2014.{{cite web | title=Drug Approval Package: Farxiga (dapagliflozin) Tablets NDA #202293 | website=U.S. Food and Drug Administration (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000TOC.cfm | access-date=5 May 2020 | archive-date=19 September 2020 | archive-url=https://web.archive.org/web/20200919132309/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000TOC.cfm | url-status=dead }}

In 2020, the US FDA expanded the indications for dapagliflozin to include treatment for adults with heart failure with reduced ejection fraction to reduce the risk of cardiovascular death and hospitalization for heart failure. It is the first in this particular drug class, sodium-glucose co-transporter 2 inhibitors, to be approved to treat adults with New York Heart Association's functional class II-IV heart failure with reduced ejection fraction.

The results of the DAPA-HF and DECLARE-TIMI 58 clinical trials demonstrated the efficacy of dapagliflozin compared to placebo in improving survival in adults with heart failure with reduced ejection fraction by 17%. They both showed a reduction in the number of hospitalizations from worsening heart failure, cardiovascular death and all-cause mortality.{{cite journal | vauthors = McMurray JJ, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CE, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM | title = Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction | journal = The New England Journal of Medicine | volume = 381 | issue = 21 | pages = 1995–2008 | date = November 2019 | pmid = 31535829 | doi = 10.1056/NEJMoa1911303 | s2cid = 202687033 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Kato ET, Silverman MG, Mosenzon O, Zelniker TA, Cahn A, Furtado RH, Kuder J, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JP, Bonaca MP, Ruff CT, Desai AS, Goto S, Johansson PA, Gause-Nilsson I, Johanson P, Langkilde AM, Raz I, Sabatine MS, Wiviott SD | title = Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus | journal = Circulation | volume = 139 | issue = 22 | pages = 2528–2536 | date = May 2019 | pmid = 30882238 | doi = 10.1161/CIRCULATIONAHA.119.040130 | s2cid = 81977866 | doi-access = free | title-link = doi }}

The safety and effectiveness of dapagliflozin were evaluated in a randomized, double-blind, placebo-controlled study of 4,744 participants. The average age of participants was 66 years and more participants were male (77%) than female. To determine the drug's effectiveness, investigators examined the occurrence of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits. Participants were randomly assigned to receive a once-daily dose of either 10 mg of dapagliflozin or a placebo (inactive treatment). After about 18 months, people who received dapagliflozin had fewer cardiovascular deaths, hospitalizations for heart failure, and urgent heart-failure visits than those receiving the placebo.

In July 2020, the FDA granted AstraZeneca a Fast Track Designation in the US for the development of dapagliflozin to reduce the risk of hospitalization for heart failure or cardiovascular death in adults following a heart attack.{{cite press release |date=16 July 2020|title=FARXIGA Granted Fast Track Designation in the US for Heart Failure Following Acute Myocardial Infarction Leveraging an Innovative Registry-Based Trial Design|url=https://www.businesswire.com/news/home/20200716005568/en/FARXIGA-Granted-Fast-Track-Designation-Heart-Failure|access-date=20 July 2020|publisher=AstraZeneca | via=Business Wire|archive-date=20 July 2020|archive-url=https://web.archive.org/web/20200720074439/https://www.businesswire.com/news/home/20200716005568/en/FARXIGA-Granted-Fast-Track-Designation-Heart-Failure|url-status=live}}

In August 2020, detailed results from the Phase III DAPA-CKD trial reportedly showed that dapagliflozin on top of standard of care reduced the composite measure of worsening of renal function or risk of cardiovascular or renal death by 39% compared to placebo (p<0.0001) in patients with chronic kidney disease stages 2–4 and elevated urinary albumin excretion. The results were consistent in patients both with and without type{{nbsp}}2 diabetes.{{cite press release|url = https://www.businesswire.com/news/home/20200830005009/en/FARXIGA-Demonstrated-Unprecedented-Reduction-Risk-Kidney-Failure|title = FARXIGA Demonstrated Unprecedented Reduction in the Risk of Kidney Failure and Cardiovascular or Renal Death in Patients with Chronic Kidney Disease in the Phase III DAPA-CKD Trial|publisher=AstraZeneca | via=Business Wire |date = 30 August 2020|access-date = 4 September 2020|archive-date = 31 August 2020|archive-url = https://web.archive.org/web/20200831083947/https://www.businesswire.com/news/home/20200830005009/en/FARXIGA-Demonstrated-Unprecedented-Reduction-Risk-Kidney-Failure|url-status = live}}

In April 2021, the FDA expanded the indications for dapagliflozin to include reducing the risk of kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease who are at risk of disease progression. The efficacy of dapagliflozin to improve kidney outcomes and reduce cardiovascular death in people with chronic kidney disease was evaluated in a multicenter, double-blind study of 4,304 participants.

In February 2023, the EU authorized dapagliflozin for extended use to cover heart failure patients across the full spectrum of left ventricular ejection fraction (LVEF), including those with mildly reduced and preserved ejection fraction.{{cite web |title=Forxiga approved in EU for chronic heart failure |url=https://www.europeanpharmaceuticalreview.com/news/179288/forxiga-approved-in-eu-for-chronic-heart-failure/ |access-date=9 February 2023 |website=European Pharmaceutical Review }}{{cite web |title=Dapagliflozin Gets Expanded Heart Failure Indication in Europe |url=https://www.medscape.com/viewarticle/988034 |access-date=9 February 2023 |website=Medscape }}

A generic version of dapagliflozin was approved by the US FDA in February 2022,{{cite web | title=Drugs@FDA: Dapagliflozin | website=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=211582 | access-date=25 March 2022 | archive-date=25 March 2022 | archive-url=https://web.archive.org/web/20220325070735/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=211582 | url-status=dead }} but cannot be sold until October 2025.{{cite web |url=https://generics.pharmaintelligence.informa.com/GB151678/Patent-Blocks-Zydus-After-Landmark-US-Approval-For-Dapagliflozin |title=Patent Blocks Zydus After Landmark US Approval For Dapagliflozin | vauthors = Rudge D |work=Generics Bulletin | date = 24 February 2022 |access-date=8 June 2022 |archive-date=10 June 2022 |archive-url=https://web.archive.org/web/20220610025419/https://generics.pharmaintelligence.informa.com/GB151678/Patent-Blocks-Zydus-After-Landmark-US-Approval-For-Dapagliflozin |url-status=live }}{{cite web | title=Dapagliflozin – USA | date=15 October 2021 | url=https://www.pharmaipcircle.com/uncategorized/dapagliflozin-usa/ | access-date=8 June 2022 | archive-date=10 June 2022 | archive-url=https://web.archive.org/web/20220610025412/https://www.pharmaipcircle.com/uncategorized/dapagliflozin-usa/ | url-status=live }} A generic version was approved in Canada in May 2023.{{cite press release | title=JAMP Pharma Group receives Health Canada approval for PrJAMP Dapagliflozin, a new generic alternative for the treatment of type 2 diabetes | publisher=JAMP Pharma | via=Newswire | date=16 May 2023 | url=https://www.newswire.ca/news-releases/jamp-pharma-group-receives-health-canada-approval-for-prjamp-dapagliflozin-a-new-generic-alternative-for-the-treatment-of-type-2-diabetes-893001974.html | access-date=17 June 2023 }}

In January 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for a generic version of Forxiga, which has been authorized in the EU since November 2012.{{cite web | title=Dapagliflozin Viatris: Pending EC decision | website=European Medicines Agency | date=26 January 2023 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/dapagliflozin-viatris | access-date=29 January 2023 | archive-date=27 January 2023 | archive-url=https://web.archive.org/web/20230127225407/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/dapagliflozin-viatris | url-status=dead }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Dapagliflozin Viatris was authorized for medical use in the European Union in March 2023.{{cite web | title=Dapagliflozin Viatris EPAR | website=European Medicines Agency | date=4 April 2023 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/dapagliflozin-viatris | access-date=17 June 2023 }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

A systematic review concluded that dapagliflozin reduced heart failure hospitalization, cardiovascular death, and all-cause mortality in people with HFrEF (i.e., congestive heart failure) and diabetes.{{cite journal | vauthors = Zhai M, Du X, Liu C, Xu H | title = The Effects of Dapagliflozin in Patients With Heart Failure Complicated With Type 2 Diabetes: A Meta-Analysis of Placebo-Controlled Randomized Trials | journal = Frontiers in Clinical Diabetes and Healthcare | volume = 2 | pages = 703937 | date = 30 June 2021 | pmid = 36994345 | pmc = 10012068 | doi = 10.3389/fcdhc.2021.703937 | doi-access = free | title-link = doi }}

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