TY - JOUR
T1 - Effect of sodium-glucose cotransporter 2 inhibitors on cardiovascular and kidney outcomes—Systematic review and meta-analysis of randomized placebo-controlled trials
T2 - SGLT2i—Cardiovascular and Kidney Outcomes
AU - Salah, Husam M.
AU - Al'Aref, Subhi J.
AU - Khan, Muhammad Shahzeb
AU - Al-Hawwas, Malek
AU - Vallurupalli, Srikanth
AU - Mehta, Jawahar L.
AU - Mounsey, J. Paul
AU - Greene, Stephen J.
AU - McGuire, Darren K.
AU - Lopes, Renato D.
AU - Fudim, Marat
N1 - Funding Information:
Fudim: Supported by the Mario Family Award, Translating Duke Health Award; Duke Medicine Chair's Award, consulting fees from AstraZeneca, AxonTherapies, CVRx, Daxor, Edwards LifeSciences, Galvani, NXT Biomedical and Respicardia.
Funding Information:
None. Al?Aref: Supported by NIH 2R01 HL127661-05, receives royalty fees from Elsevier. Mehta has previously served as consultant to Bayer, Boehringer Ingelheim, AstraZeneca, MedImmmune and Pfizer; and received grant support from Bayer, Boehringer Ingelheim and AstraZeneca. Current grant support from Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development (Washington, DC, USA) (grant No BX-000282-05). Greene: has received a Heart Failure Society of America/ Emergency Medicine Foundation Acute Heart Failure Young Investigator Award funded by Novartis; receives research support from Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis; serves on advisory boards for Amgen and Cytokinetics; and serves as a consultant for Amgen and Merck. McGuire: has received personal fees for trial leadership and/or consultancy from Boehringer Ingelheim, Janssen Research and Development LLC, Sanofi US, Merck Sharp and Dohme Corp. Eli Lilly USA, Novo Nordisk, GlaxoSmithKline, AstraZeneca, Lexicon Pharmaceuticals, Eisai, Pfizer, Metavant, Applied Therapeutics, Afimmune and Esperion. Lopes: research grants and personal fees from Bristol-Myers Squibb and Pfizer, personal fees from Boehringer Ingelheim and Bayer AG and grants from Amgen Inc. GlaxoSmithKline, Medtronic PLC, and Sanofi Aventis outside the submitted work. Fudim: Supported by the Mario Family Award, Translating Duke Health Award; Duke Medicine Chair's Award, consulting fees from AstraZeneca, AxonTherapies, CVRx, Daxor, Edwards LifeSciences, Galvani, NXT Biomedical and Respicardia. All other authors report no relevant disclosures. Funding Sources: None.
Funding Information:
Greene: has received a Heart Failure Society of America/ Emergency Medicine Foundation Acute Heart Failure Young Investigator Award funded by Novartis; receives research support from Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis; serves on advisory boards for Amgen and Cytokinetics; and serves as a consultant for Amgen and Merck.
Funding Information:
Mehta has previously served as consultant to Bayer, Boehringer Ingelheim, AstraZeneca, MedImmmune and Pfizer; and received grant support from Bayer, Boehringer Ingelheim and AstraZeneca. Current grant support from Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development (Washington, DC, USA) (grant No BX-000282-05).
Funding Information:
Al′Aref: Supported by NIH 2R01 HL127661-05, receives royalty fees from Elsevier.
Funding Information:
Lopes: research grants and personal fees from Bristol-Myers Squibb and Pfizer, personal fees from Boehringer Ingelheim and Bayer AG and grants from Amgen Inc., GlaxoSmithKline, Medtronic PLC, and Sanofi Aventis outside the submitted work.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/2
Y1 - 2021/2
N2 - Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use is associated with improved cardiovascular and kidney outcomes. However, the magnitude and potential heterogeneity of effect across patients with varying types of cardiometabolic and kidney disease is unclear. To examine the effect of SGLT2i on cardiovascular and kidney outcomes among patients with type 2 diabetes mellitus (T2DM), and independent of T2DM status, among patients with heart failure (HF), and chronic kidney disease. Method: Medline, Embase, Cochrane library and scientific conferences were searched from inception till September 24, 2020 for randomized controlled trials comparing cardiovascular and kidney outcomes between SGLT2i and placebo. Random effects hazard ratios (HR) with 95% confidence intervals (CIs) were calculated. Results: Eight trials with a combined 59,747 patients were included. In the overall population, SGLT2i reduced the risk of all-cause mortality (HR 0.84; 95% CI [0.78-0.91]), cardiovascular mortality (HR 0.84; 95% CI [0.76-0.93]) hospitalization for HF (HR 0.69; 95% CI [0.64-0.74]), myocardial infarction (HR 0.91; 95% CI [0.84-0.99]), and composite kidney outcome (HR 0.62; 95% CI [0.56-0.70]). There was no significant effect on the risk of stroke (HR 0.98; 95% CI [0.86-1.11]). Results were consistent across subgroups stratified by diabetes and HF status. SGLT2i use was not associated with a greater risk of hypoglycemia (OR 0.92; 95% CI [0.84-1.01]) or amputation (OR 1.25; 95% CI [0.97-1.62]). There were 64 diabetic ketoacidosis events with SGLT2i use and 18 with placebo (OR 2.86; 95% CI [1.39-5.86]). Conclusions: In patients with cardiometabolic and kidney disease, SGLT2i improved cardiovascular and kidney outcomes, regardless of T2DM, HF, and/or CKD status. The magnitude of risk reduction was largest for hospitalization for HF and progression of kidney disease, more modest for mortality and MI and absent for stroke.
AB - Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use is associated with improved cardiovascular and kidney outcomes. However, the magnitude and potential heterogeneity of effect across patients with varying types of cardiometabolic and kidney disease is unclear. To examine the effect of SGLT2i on cardiovascular and kidney outcomes among patients with type 2 diabetes mellitus (T2DM), and independent of T2DM status, among patients with heart failure (HF), and chronic kidney disease. Method: Medline, Embase, Cochrane library and scientific conferences were searched from inception till September 24, 2020 for randomized controlled trials comparing cardiovascular and kidney outcomes between SGLT2i and placebo. Random effects hazard ratios (HR) with 95% confidence intervals (CIs) were calculated. Results: Eight trials with a combined 59,747 patients were included. In the overall population, SGLT2i reduced the risk of all-cause mortality (HR 0.84; 95% CI [0.78-0.91]), cardiovascular mortality (HR 0.84; 95% CI [0.76-0.93]) hospitalization for HF (HR 0.69; 95% CI [0.64-0.74]), myocardial infarction (HR 0.91; 95% CI [0.84-0.99]), and composite kidney outcome (HR 0.62; 95% CI [0.56-0.70]). There was no significant effect on the risk of stroke (HR 0.98; 95% CI [0.86-1.11]). Results were consistent across subgroups stratified by diabetes and HF status. SGLT2i use was not associated with a greater risk of hypoglycemia (OR 0.92; 95% CI [0.84-1.01]) or amputation (OR 1.25; 95% CI [0.97-1.62]). There were 64 diabetic ketoacidosis events with SGLT2i use and 18 with placebo (OR 2.86; 95% CI [1.39-5.86]). Conclusions: In patients with cardiometabolic and kidney disease, SGLT2i improved cardiovascular and kidney outcomes, regardless of T2DM, HF, and/or CKD status. The magnitude of risk reduction was largest for hospitalization for HF and progression of kidney disease, more modest for mortality and MI and absent for stroke.
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U2 - 10.1016/j.ahj.2020.10.064
DO - 10.1016/j.ahj.2020.10.064
M3 - Review article
C2 - 33214130
AN - SCOPUS:85096157227
SN - 0002-8703
VL - 232
SP - 10
EP - 22
JO - American heart journal
JF - American heart journal
ER -