Barriers to early diagnosis of chronic kidney disease and use of sodium-glucose cotransporter-2 inhibitors for renal protection: A comprehensive review and call to action
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, přehledy
Grantová podpora
Boehringer Ingelheim International GmbH
PubMed
39140231
DOI
10.1111/dom.15789
Knihovny.cz E-zdroje
- Klíčová slova
- SGLT2 inhibitor, chronic kidney disease, dapagliflozin, empagliflozin, renal protection, type 2 diabetes,
- MeSH
- benzhydrylové sloučeniny terapeutické užití MeSH
- časná diagnóza * MeSH
- chronická renální insuficience * farmakoterapie diagnóza MeSH
- diabetes mellitus 2. typu * farmakoterapie komplikace MeSH
- diabetické nefropatie * diagnóza prevence a kontrola farmakoterapie MeSH
- glifloziny * terapeutické užití MeSH
- glukosidy terapeutické užití MeSH
- hodnoty glomerulární filtrace účinky léků MeSH
- lidé MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- benzhydrylové sloučeniny MeSH
- empagliflozin MeSH Prohlížeč
- glifloziny * MeSH
- glukosidy MeSH
Chronic kidney disease (CKD) affects approximately 13% of people globally, including 20%-48% with type 2 diabetes (T2D), resulting in significant morbidity, mortality, and healthcare costs. There is an urgent need to increase early screening and intervention for CKD. We are experts in diabetology and nephrology in Central Europe and Israel. Herein, we review evidence supporting the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for kidney protection and discuss barriers to early CKD diagnosis and treatment, including in our respective countries. SGLT2 inhibitors exert cardiorenal protective effects, demonstrated in the renal outcomes trials (EMPA-KIDNEY, DAPA-CKD, CREDENCE) of empagliflozin, dapagliflozin, and canagliflozin in patients with CKD. EMPA-KIDNEY demonstrated cardiorenal efficacy across the broadest renal range, regardless of T2D status. Renoprotective evidence also comes from large real-world studies. International guidelines recommend first-line SGLT2 inhibitors for patients with T2D and estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m2, and that glucagon-like peptide-1 receptor agonists may also be administered if required for additional glucose control. Although these guidelines recommend at least annual eGFR and urine albumin-to-creatinine ratio screening for patients with T2D, observational studies suggest that only half are screened. Diagnosis is hampered by asymptomatic early CKD and under-recognition among patients with T2D and clinicians, including limited knowledge/use of guidelines and resources. Based on our experience and on the literature, we recommend robust screening programmes, potentially with albuminuria self-testing, and SGLT2 inhibitor reimbursement at general practitioner (GP) and specialist levels. High-tech tools (artificial intelligence, smartphone apps, etc.) are providing exciting opportunities to identify high-risk individuals, self-screen, detect abnormalities in images, and assist with prescribing and treatment adherence. Better education is also needed, alongside provision of concise guidelines, enabling GPs to identify who would benefit from early initiation of renoprotective therapy; although, regardless of current renal function, cardiorenal protection is provided by SGLT2 inhibitor therapy.
Department of Diabetology and Internal Medicine Medical University of Warsaw Warsaw Poland
Department of Endocrinology Medical University Sofia Sofia Bulgaria
Department of Internal Medicine 3rd Faculty of Medicine Charles University Prague Czech Republic
Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
Department of Medicine and Oncology Semmelweis University Budapest Hungary
Department of Metabolic Diseases Jagiellonian University Medical College Kraków Poland
Diabetes and Endocrinology Clinic Clalit Medical Services Ramat Gan Israel
Diabetes Clinic Pius Brinzeu Emergency Hospital Timisoara Romania
Faculty of Medicine Hebrew University of Jerusalem Jerusalem Israel
Hospital of Internal Medicine Brüder Linz Linz Austria
Institute for Cardiovascular and Metabolic Research Linz Austria
Regeneron Pharmaceuticals Tarrytown New York USA
University Digestive Health Care Centre Basel Clarunis Basel Switzerland
University Hospital Královské Vinohrady Prague Czech Republic
Zobrazit více v PubMed
Chapter 1: definition and classification of CKD. Kidney Int. Suppl. 2013;3:19‐62.
de Boer IH, Khunti K, Sadusky T, et al. Diabetes Management in Chronic Kidney Disease: a consensus report by the American Diabetes Association (ADA) and kidney disease: improving global outcomes (KDIGO). Diabetes Care. 2022;45:3075‐3090.
Bikbov B, Purcell CA, Levey AS, et al. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the global burden of disease study 2017. Lancet. 2020;395:709‐733.
Hill NR, Fatoba ST, Oke JL, et al. Global prevalence of chronic kidney disease: a systematic review and meta‐analysis. PLoS One. 2016;11:e0158765.
Sundström J, Bodegard J, Bollmann A, et al. Prevalence, outcomes, and cost of chronic kidney disease in a contemporary population of 2·4 million patients from 11 countries: the CaReMe CKD study. Lancet reg Health Eur. 2022;20:100438.
Chu L, Fuller M, Jervis K, Ciaccia A, Abitbol A. Prevalence of chronic kidney disease in type 2 diabetes: the Canadian REgistry of chronic kidney disease in diabetes outcomes (CREDO) study. Clin Ther. 2021;43:1558‐1573.
Khunti K, Charbonnel B, Chen H, et al. Prevalence and progression of chronic kidney disease among patients with type 2 diabetes: insights from the DISCOVER study. Diabetes Obes Metab. 2021;23:1956‐1960.
Cook S, Schmedt N, Broughton J, Kalra PA, Tomlinson LA, Quint JK. Characterising the burden of chronic kidney disease among people with type 2 diabetes in England: a cohort study using the clinical practice research datalink. BMJ Open. 2023;13:e065927.
Arnold SV, Kosiborod M, Wang J, Fenici P, Gannedahl G, LoCasale RJ. Burden of cardio‐renal‐metabolic conditions in adults with type 2 diabetes within the diabetes collaborative registry. Diabetes Obes Metab. 2018;20:2000‐2003.
Cherney DZI, Repetto E, Wheeler DC, et al. Impact of cardio‐renal‐metabolic comorbidities on cardiovascular outcomes and mortality in type 2 diabetes mellitus. Am J Nephrol. 2020;51:74‐82.
Vora J, Cherney D, Kosiborod MN, et al. Inter‐relationships between cardiovascular, renal and metabolic diseases: underlying evidence and implications for integrated interdisciplinary care and management. Diabetes Obes Metab. 2024;26:1567‐1581. doi:10.1111/dom.15485
Sicras‐Mainar A, Sicras‐Navarro A, Palacios B, et al. Epidemiology and resource use in Spanish type 2 diabetes patients without previous cardiorenal disease: CaReMe Spain study summary. Endocrinol Diabetes Nutr. 2022;69:509‐519.
Afkarian M, Sachs MC, Kestenbaum B, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24:302‐308.
Shubrook JH, Neumiller JJ, Wright E. Management of chronic kidney disease in type 2 diabetes: screening, diagnosis and treatment goals, and recommendations. Postgrad Med. 2022;134:376‐387.
Bramlage P, Lanzinger S, Tittel SR, et al. Guidelines adherence in the prevention and management of chronic kidney disease in patients with diabetes mellitus on the background of recent European recommendations: a registry‐based analysis. BMC Nephrol. 2021;22:184.
Hagnäs M, Sundqvist H, Jokelainen J, et al. The prevalence of chronic kidney disease and screening of renal function in type 2 diabetic patients in Finnish primary healthcare. Prim Care Diabetes. 2020;14:639‐644.
Chu L, Bhogal SK, Lin P, et al. AWAREness of diagnosis and treatment of chronic kidney disease in adults with type 2 diabetes (AWARE‐CKD in T2D). Can J Diabetes. 2022;46:464‐472.
McGill JB, Haller H, Roy‐Chaudhury P, et al. Making an impact on kidney disease in people with type 2 diabetes: the importance of screening for albuminuria. BMJ Open Diabetes Res Care. 2022;10:e002806.
Correa‐Rotter R, Méndez Durán A, Vallejos A, et al. Unmet needs of CKD in Latin America: a review from expert virtual working group. Kidney Int Rep. 2023;8:954‐967.
Sperati CJ, Soman S, Agrawal V, et al. Primary care physicians' perceptions of barriers and facilitators to management of chronic kidney disease: a mixed methods study. PLoS One. 2019;14:e0221325.
Wang H‐Y, Ding GH, Lin H, et al. Influence of doctors' perception on the diagnostic status of chronic kidney disease: results from 976 409 individuals with electronic health records in China. Clin Kidney J. 2021;14:2428‐2436.
Otieno FCF, Ogola EN, Kimando MW, Mutai K. The burden of unrecognised chronic kidney disease in patients with type 2 diabetes at a county hospital clinic in Kenya: implications to care and need for screening. BMC Nephrol. 2020;21:73.
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380:2295‐2306.
Heerspink HJL, Stefánsson BV, Correa‐Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383:1436‐1446.
The EMPA‐KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388:117‐127.
Davies MJ, Drexel H, Jornayvaz FR, Pataky Z, Seferović PM, Wanner C. Cardiovascular outcomes trials: a paradigm shift in the current management of type 2 diabetes. Cardiovasc Diabetol. 2022;21:144.
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117‐2128.
Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323‐334.
Neal B, Perkovic V, Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:2099.
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347‐357.
ElSayed NA, Aleppo G, Aroda VR, et al. 11. Chronic kidney disease and risk management: standards of Care in Diabetes—2023. Diabetes Care. 2023;46:S191‐S202.
Manski‐Nankervis J‐AE, Thuraisingam S, Lau P, et al. Screening and diagnosis of chronic kidney disease in people with type 2 diabetes attending Australian general practice. Aust J Prim Health. 2018;24:280‐286.
Zanchi A, Jehle AW, Lamine F, et al. Diabetic kidney disease in type 2 diabetes: a consensus statement from the swiss societies of diabetes and nephrology. Swiss Med Wkly. 2023;153:40004.
Araszkiewicz A, Bandurska‐Stankiewicz E, Borys S, et al. Guidelines on the management of patients with diabetes a position of diabetes Poland. Curr Top Diabetes. 2023;3:1‐133.
Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC guidelines on diabetes, pre‐diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020;41:255‐323.
Symptoms Chronic kidney disease. https://www.nhs.uk/conditions/kidney-disease/symptoms/
Prázný M, Suplotova L, Gumprecht J, et al. Real‐world characteristics, modern antidiabetic treatment patterns, and comorbidities of patients with type 2 diabetes in central and Eastern Europe: retrospective cross‐sectional and longitudinal evaluations in the CORDIALLY® study. Cardiovasc Diabetol. 2022;21:203.
Schernthaner G, Shehadeh N, Ametov AS, et al. Worldwide inertia to the use of cardiorenal protective glucose‐lowering drugs (SGLT2i and GLP‐1 RA) in high‐risk patients with type 2 diabetes. Cardiovasc Diabetol. 2020;19:185.
Jeong SJ, Lee SE, Shin DH, Park IB, Lee HS, Kim KA. Barriers to initiating SGLT2 inhibitors in diabetic kidney disease: a real‐world study. BMC Nephrol. 2021;22:177.
Thomas MC, Neuen BL, Twigg SM, Cooper ME, Badve SV. SGLT2 inhibitors for patients with type 2 diabetes and CKD: a narrative review. Endocr Connect. 2023;12:e230005. doi:10.1530/EC‐23‐0005
Sourij H, Edlinger R, Prischl FC, et al. Diabetic kidney disease (update 2023): position paper of the Austrian diabetes association and the Austrian Society for Nephrology. Wien Klin Wochenschr. 2023;135:182‐194.
Pelikánová T, Viklický O, Rychlík I, et al. Doporučené postupy při diabetickém onemocnění ledvin. Klin Biochem Metab. 2021;29:104‐116.
Chronic kidney disease: Screening. https://bestpractice.bmj.com/topics/en-gb/84/screening
ISN‐KDIGO Early Screening Booklet. https://www.theisn.org/wp‐content/uploads/2023/02/ISN_KDIGO_EarlyScreeningBooklet_PRINT_Updated.pdf
eGFR Calculator. https://www.kidney.org/professionals/kdoqi/gfr_calculator
Delgado C, Baweja M, Crews DC, et al. A unifying approach for GFR estimation: recommendations of the NKF‐ASN task force on reassessing the inclusion of race in diagnosing kidney disease. Am J Kidney Dis. 2022;79:268‐288.e1.
Navaneethan SD, Zoungas S, Caramori ML, et al. Diabetes Management in Chronic Kidney Disease: synopsis of the KDIGO 2022 clinical practice guideline update. Ann Intern Med. 2023;176:381‐387.
Voors AA, Angermann CE, Teerlink JR, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022;28:568‐574.
Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J med. 2021;385:1451‐1461. doi:10.1056/NEJMoa2107038
Packer M, Butler J, Zannad F, et al. Effect of empagliflozin on worsening heart failure events in patients with heart failure and a preserved ejection fraction: the EMPEROR‐preserved trial. Circulation. 2021;144:1284‐1294. doi:10.1161/CIRCULATIONAHA.121.056824
Packer M, Anker SD, Butler J, et al. Effect of empagliflozin on the clinical stability of patients with heart failure and a reduced ejection fraction: the EMPEROR‐reduced trial. Circulation. 2021;143:326‐336.
McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J med. 2019;381:1995‐2008.
Petrie MC, Verma S, Docherty KF, et al. Effect of dapagliflozin on worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes. JAMA. 2020;323:1353‐1368.
Rådholm K, Figtree G, Perkovic V, et al. Canagliflozin and heart failure in type 2 diabetes mellitus: results from the CANVAS program. Circulation. 2018;138:458‐468.
ElSayed NA, Aleppo G, Aroda VR, et al. 9. Pharmacologic approaches to glycemic treatment: standards of Care in Diabetes—2023. Diabetes Care. 2023;46:S140‐S157.
Ishibashi T, Morita S, Furuta H, Nishi M, Matsuoka T‐A. Renoprotective potential of concomittant medications with SGLT2 inhibitors and renin‐angiotensin system inhibitors in diabetic nephropathy without albuminuria: a retrospective cohort study. Sci Rep. 2023;13:16373.
AstraZeneca. https://www.forxiga.co.uk/content/dam/intelligentcontent/brands/forxiga‐uk/en/resources/pdf/SGLT2i_dosing_considerations_according_to_eGFR_when_treating_T2D_HF_or_CKD_April_2023_A4.pdf#:∼:text=The%20glucose%20lowering%20eficacy%20of%20dapagliflozin%20is%20dependent,likely%20absent%20in%20patients%20with%20severe%20renal%20impairment.
Boehringer Ingelheim. https://pro.boehringer‐ingelheim.com/us/products/jardiance/cv‐disease/efficacy#:∼:text=JARDIANCE%20is%20not%20recommended%20for%20use%20to%20improve,this%20setting%20based%20upon%20its%20mechanism%20of%20action.
Ninčević V, Omanović Kolarić T, Roguljić H, Kizivat T, Smolić M, Bilić Ćurčić I. Renal benefits of SGLT 2 inhibitors and GLP‐1 receptor agonists: evidence supporting a paradigm shift in the medical Management of Type 2 diabetes. Int J Mol Sci. 2019;20:5831.
European Kidney Patients Federation. The realities of living with CKD: People with T2D and CKD speak up. https://ekpf.eu/wp‐content/uploads/2023/03/EKPF‐Designed‐Patient‐Insights‐Report_FINAL.pdf
Vanholder R, Annemans L, Bello AK, et al. Fighting the unbearable lightness of neglecting kidney health: the decade of the kidney. Clin Kidney J. 2021;14:1719‐1730.
Stempniewicz N, Vassalotti JA, Cuddeback JK, et al. Chronic kidney disease testing among primary care patients with type 2 diabetes across 24 U.S. health care organizations. Diabetes Care. 2021;44:2000‐2009.
Chudek J, Wieczorowska‐Tobis K, Zejda J, et al. The prevalence of chronic kidney disease and its relation to socioeconomic conditions in an elderly polish population: results from the national population‐based study PolSenior. Nephrol Dial Transplant. 2014;29:1073‐1082.
Stolpe S, Kowall B, Scholz C, Stang A, Blume C. High unawareness of chronic kidney disease in Germany. Int J Environ Res Public Health. 2021;18:11752.
Ministry of Health, Israel. National Program of Quality Indicators Report, Years 2015–2019. https://en.israelhealthindicators.org/_files/ugd/76a237_d825102a7f984348a6debd5bccf78768.pdf
Christ E, Czock A, Renström F, et al. Evaluation of type 2 diabetes care management in nine primary care practices before and after implementation of the criteria of good disease Management of Diabetes established by the swiss Society of Endocrinology and Diabetology. Swiss Med Wkly. 2022;152:w30197.
Kvapil M. Je nám k něčemu dobrý Národní diabetologický registr? 2022.
Betts KA, Song J, Elliott J, et al. Geographical variation in kidney function testing and associations with health care costs among patients with chronic kidney disease and type 2 diabetes. Am J Manag Care. 2022;28:S112‐S119.
Naylor KB, Tootoo J, Yakusheva O, Shipman SA, Bynum JPW, Davis MA. Geographic variation in spatial accessibility of U.S. healthcare providers. PLoS One. 2019;14:e0215016.
Pesce F, Pasculli D, Pasculli G, et al. “The disease awareness innovation network” for chronic kidney disease identification in general practice. J Nephrol. 2022;35:2057‐2065.
Suen M, Manski‐Nankervis J‐A, McBride C, Lumsden N, Hunter B. Implementing a sodium‐glucose cotransporter 2 inhibitor module with a software tool (future health today): qualitative study. JMIR Form Res. 2024;8:e50737.
Mueller C, Schürks M, Neußer T, et al. Identification of patients with elevated urine albumin‐to‐creatinine ratio levels in a type 2 diabetes mellitus cohort based on data submitted by patients via a smartphone app (SMART‐finder): protocol for an observational study. JMIR Res Protoc. 2023;12:e44996.
Green JA, Ephraim PL, Hill‐Briggs F, et al. Integrated digital health system tools to support decision making and treatment preparation in CKD: the PREPARE NOW study. Kidney Med. 2021;3:565‐575.e1.
Bravo‐Zúñiga J, Gálvez‐Inga J, Carrillo‐Onofre P, Chávez‐Gómez R, Castro‐Monteverde P. Early detection of chronic renal disease: coordinated work between primary and specialized care in an ambulatory renal network of Peru. J Bras Nefrol. 2019;41:176‐184.
Pouwels XGLV, van Mil D, Kieneker LM, et al. Cost‐effectiveness of home‐based screening of the general population for albuminuria to prevent progression of cardiovascular and kidney disease. EClinicalMedicine. 2024;68:102414.
Wu C‐C, Islam MM, Poly TN, Weng Y‐C. Artificial intelligence in kidney disease: a comprehensive study and directions for future research. Diagn Basel Switz. 2024;14:397.
O'Hara DV, Yi TW, Lee VW, Jardine M, Dawson J. Digital health technologies to support medication adherence in chronic kidney disease. Nephrology (Carlton). 2022;27:917‐924.
Skrabic R, Kumric M, Vrdoljak J, et al. SGLT2 inhibitors in chronic kidney disease: from mechanisms to clinical practice. Biomedicine. 2022;10:2458.
Marton A, Kaneko T, Kovalik JP, et al. Organ protection by SGLT2 inhibitors: role of metabolic energy and water conservation. Nat Rev Nephrol. 2021;17:65‐77.
Bhatt DL, Szarek M, Pitt B, et al. Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med. 2021;384:129‐139.
Sridhar VS, Bhatt DL, Odutayo A, et al. Sotagliflozin and kidney outcomes, kidney function, and albuminuria in T2DM and CKD: a secondary analysis of the SCORED trial. Clin J Am Soc Nephrol. 2024;19:557‐564. doi:10.2215/CJN.0000000000000414
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;12:51‐60.
EMPA‐KIDNEY Collaborative Group. Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa‐kidney trial. Lancet Diabetes Endocrinol. 2024;12:39‐50.
Heerspink HJL, Karasik A, Thuresson M, et al. Kidney outcomes associated with use of SGLT2 inhibitors in real‐world clinical practice (CVD‐REAL 3): a multinational observational cohort study. Lancet Diabetes Endocrinol. 2020;8:27‐35.
Pasternak B, Wintzell V, Melbye M, et al. Use of sodium‐glucose co‐transporter 2 inhibitors and risk of serious renal events: Scandinavian cohort study. BMJ. 2020;369. doi:10.1136/bmj.m1186
Forbes AK, Suckling RJ, Hinton W, et al. Sodium‐glucose cotransporter‐2 inhibitors and kidney outcomes in real‐world type 2 diabetes populations: a systematic review and meta‐analysis of observational studies. Diabetes Obes Metab. 2023;25:2310‐2330. doi:10.1111/dom.15111
Koh ES, Han K, Nam YS, et al. Renal outcomes and all‐cause death associated with sodium‐glucose co‐transporter‐2 inhibitors versus other glucose‐lowering drugs (CVD‐REAL 3 Korea). Diabetes Obes Metab. 2021;23:455‐466.
Melzer‐Cohen C, Schechter M, Rozenberg A, et al. Long‐term, real‐world, kidney function changes with SGLT2i versus DPP4i type 2 diabetes without cardiovascular or kidney disease. Clin J Am Soc Nephrol. 2023;18:1153‐1162. doi:10.2215/CJN.0000000000000218
Schechter M, Melzer Cohen C, Zelter T, et al. Risk of hospitalization with sodium‐glucose cotransporter‐2 inhibitors versus dipeptidyl peptidase‐4 inhibitors in patients with type 2 diabetes lacking evidence of chronic kidney disease: real‐world data. Diabetes Obes Metab. 2023;25:3054‐3058. doi:10.1111/dom.15172
Karasik A, Lanzinger S, Chia‐Hui Tan E, et al. Empagliflozin cardiovascular and renal effectiveness and safety compared to dipeptidyl peptidase‐4 inhibitors across 11 countries in Europe and Asia: results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study. Diabetes Metab. 2023;49:101418.
Kosiborod M, Cavender MA, Fu AZ, et al. Lower risk of heart failure and death in patients initiated on sodium‐glucose Cotransporter‐2 inhibitors versus other glucose‐lowering drugs: the CVD‐REAL study (comparative effectiveness of cardiovascular outcomes in new users of sodium‐glucose Cotransporter‐2 inhibitors). Circulation. 2017;136:249‐259.
Kosiborod M, Lam CSP, Kohsaka S, et al. Cardiovascular events associated with SGLT‐2 inhibitors versus other glucose‐lowering drugs: the CVD‐REAL 2 study. J Am Coll Cardiol. 2018;71:2628‐2639.