TY - JOUR
T1 - Sglt2 inhibition for ckd and cardiovascular disease in type 2 diabetes
T2 - Report of a scientific workshop sponsored by the national kidney foundation
AU - Tuttle, Katherine R.
AU - Brosius, Frank C.
AU - Cavender, Matthew A.
AU - Fioretto, Paola
AU - Fowler, Kevin J.
AU - Heerspink, Hiddo J.L.
AU - Manley, Tom
AU - McGuire, Darren K.
AU - Molitch, Mark E.
AU - Mottl, Amy K.
AU - Perreault, Leigh
AU - Rosas, Sylvia E.
AU - Rossing, Peter
AU - Sola, Laura
AU - Vallon, Volker
AU - Wanner, Christoph
AU - Perkovic, Vlado
N1 - Funding Information:
The workshop sponsors had no role in the development of the workshop agenda or objectives. The sponsors were restricted from viewing any part of the workshop report manuscript until it was accepted for publication and therefore had no role in the content developed for this report. Financial Disclosure. K.R.T. is supported by National Institutes of Health (NIH) grants and a Centers for Disease Control and Prevention contract and has served as a consultant for Eli Lilly & Co, Boehringer Ingelheim, AstraZeneca, Gilead, Goldfinch Bio, Novo Nordisk, Bayer, and Janssen. M.A.C. has received research support (nonsalary) from Amgen, AstraZeneca, Bristol Myers Squibb, Chiesi, CSL Behring, GlaxoSmithKline, and Novartis; research support (salary) from Novo Nordisk; and consulting fees from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Edwards Lifesciences, and Merck. L.P. has received personal fees from speaking and/or consulting from Novo Nordisk, Sanofi, AstraZeneca, Boehringer Ingelheim, Janssen, Merck, and UpToDate. V.V. reports grants from the NIH and has served as a consultant and received honoraria from Bayer, Boehringer Ingelheim, Eli Lilly & Co, Janssen Pharmaceutical, Merck, and Retrophin and grant support for investigator-initiated research from AstraZeneca, Bayer, Boehringer Ingelheim, Fresenius, and Janssen Pharmaceutical. P.R. reports having given lectures for AstraZeneca, Bayer, Novo Nordisk, and Boehringer Ingelheim and has served as a consultant for AbbVie, AstraZeneca, Bayer, Eli Lilly & Co, Boehringer Ingelheim, Astellas, Gilead, Mundipharma, Vifor, and Novo Nordisk, all fees given to Steno Diabetes Center Copenhagen. F.C.B. reports grants from the NIH and the Juvenile Diabetes Research Foundation; the University of Michigan has contracted with Gilead for his consulting services. P.F. reports receiving personal fees for advisory boards or scientific presentations from AstraZeneca, Mundipharma, Boehringer Ingelheim, Eli Lilly & Co, and Novartis. K.J.F. is a consultant for Responsum Health, Bayer, Gilead, Chiesi, Talaris, Retrophin, Otsuka, and Veloxis. H.J.L.H. has served as a consultant for Abbvie, AstraZeneca, Boehringer Ingel-heim, Fresenius, Gilead, Janssen, Merck, Mundipharma, Mitsubishi-Tanabe, and Retrophin and received grant support from Abbvie, AstraZeneca, Boehringer Ingelheim, and Janssen. A.K.M. has contracts with Aurinia, Boehringer Ingelheim, Calliditas, Duke Clinical Research Institute, and Pfizer; has been a member of the scientific advisory board for AstraZeneca; and has consultancy agreements with Proteomics Int. S.E.R. reports grants from the NIH, Bayer, and Ironwood Pharmaceuticals and has participated in advisory boards for Reata and Bayer Healthcare. M.E.M. reports grants from the National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Novartis, and Novo Nordisk and consulting fees from Merck, Pfizer, and Janssen. D.K.M. has received honoraria for clinical trial leadership from AstraZeneca, Sanofi Aventis, Janssen, Boehringer Ingelheim, Merck & Co, Pfizer, Novo Nordisk, Lexicon, Eisai Inc, GlaxoSmithKline, Lilly USA, and Esperion and honoraria for consultancy from AstraZeneca, Sanofi Aventis, Lilly USA, Boehringer Ingelheim, Merck & Co, Novo Nordisk, Metavant, Applied Therapeutics, and Afimmune. C.W. has received honoraria from AstraZeneca, Sanofi, Boehringer Ingelheim, Merck, Eli Lilly & Co, and Mundipharma. T.M. is employed by the NKF. V.P. has received fees for advisory boards, steering committee roles, or scientific presentations from Abbvie, Astellas, AstraZeneca, Bayer, Baxter, BMS, Boehringer Ingelheim, Chinook, Dimerix, Durect, Eli Lilly & Co, Gilead, GSK, Janssen, Merck, Mitsubishi Tanabe, Mundipharma, Novartis, Novo Nordisk, Pfizer, Pharmalink, Relypsa, Retrophin, Sanofi, Servier, Vifor, and Tricida.
Publisher Copyright:
© 2020 by the American Diabetes Association and the National Kidney Foundation.
PY - 2021
Y1 - 2021
N2 - Diabetes is the most frequent cause of chronic kidney disease (CKD), leading to nearly half of all cases of kidney failure requiring replacement therapy. The principal cause of death among patients with diabetes and CKD is cardiovascular disease (CVD). Sodium/glucose cotrans-porter 2 (SGLT2) inhibitors were developed to lower blood glucose levels by inhibiting glucose reabsorption in the proximal tubule. In clinical trials designed to dem-onstrate the CVD safety of SGLT2 inhibitors in type 2 diabetes mellitus (T2DM), consistent reductions in risks for secondary kidney disease end points (albuminuria and a composite of serum creatinine doubling or 40% estimated glomerular filtration rate decline, kidney failure, or death), along with reductions in CVD events, were ob-served. In patients with CKD, the kidney and CVD benefits of canagliflozin were established by the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial in patients with T2DM, urinary albumin-creatinine ratio >300 mg/g, and estimated glomerular filtration rate of 30 to <90 mL/ min/1.73 m2. To clarify and support the role of SGLT2 inhibitors for treatment of T2DM and CKD, the National Kidney Foundation convened a scientific workshop with an international panel of more than 80 experts. They discussed the current state of knowledge and unanswered questions in order to propose therapeutic approaches and delineate future research. SGLT2 inhibitors improve glomerular hemodynamic function and are thought to ameliorate other local and systemic mechanisms involved in the pathogenesis of CKD and CVD. SGLT2 inhibitors should be used when possible by people with T2DM to reduce risks for CKD and CVD in alignment with the clinical trial entry criteria. Important risks of SGLT2 inhibitors include euglycemic ketoacidosis, genital mycotic infections, and volume depletion. Careful consideration should be given to the balance of benefits and harms of SGLT2 inhibitors and risk mitigation strategies. Effective implementation strategies are needed to achieve widespread use of these life-saving medications.
AB - Diabetes is the most frequent cause of chronic kidney disease (CKD), leading to nearly half of all cases of kidney failure requiring replacement therapy. The principal cause of death among patients with diabetes and CKD is cardiovascular disease (CVD). Sodium/glucose cotrans-porter 2 (SGLT2) inhibitors were developed to lower blood glucose levels by inhibiting glucose reabsorption in the proximal tubule. In clinical trials designed to dem-onstrate the CVD safety of SGLT2 inhibitors in type 2 diabetes mellitus (T2DM), consistent reductions in risks for secondary kidney disease end points (albuminuria and a composite of serum creatinine doubling or 40% estimated glomerular filtration rate decline, kidney failure, or death), along with reductions in CVD events, were ob-served. In patients with CKD, the kidney and CVD benefits of canagliflozin were established by the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial in patients with T2DM, urinary albumin-creatinine ratio >300 mg/g, and estimated glomerular filtration rate of 30 to <90 mL/ min/1.73 m2. To clarify and support the role of SGLT2 inhibitors for treatment of T2DM and CKD, the National Kidney Foundation convened a scientific workshop with an international panel of more than 80 experts. They discussed the current state of knowledge and unanswered questions in order to propose therapeutic approaches and delineate future research. SGLT2 inhibitors improve glomerular hemodynamic function and are thought to ameliorate other local and systemic mechanisms involved in the pathogenesis of CKD and CVD. SGLT2 inhibitors should be used when possible by people with T2DM to reduce risks for CKD and CVD in alignment with the clinical trial entry criteria. Important risks of SGLT2 inhibitors include euglycemic ketoacidosis, genital mycotic infections, and volume depletion. Careful consideration should be given to the balance of benefits and harms of SGLT2 inhibitors and risk mitigation strategies. Effective implementation strategies are needed to achieve widespread use of these life-saving medications.
UR - http://www.scopus.com/inward/record.url?scp=85097765087&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097765087&partnerID=8YFLogxK
U2 - 10.2337/dbi20-0040
DO - 10.2337/dbi20-0040
M3 - Article
C2 - 33106255
AN - SCOPUS:85097765087
SN - 0012-1797
VL - 70
SP - 1
EP - 16
JO - Diabetes
JF - Diabetes
IS - 1
ER -