Sodium-glucose co-transporter-2 inhibitors with and without metformin: A meta-analysis of cardiovascular, kidney and mortality outcomes
Brendon L. Neuen,Clare Arnott,Vlado Perkovic,Vlado Perkovic,Gemma A. Figtree,Dick de Zeeuw,Greg Fulcher,Min Jun,Min Jun,Meg Jardine,Sophia Zoungas,Carol A. Pollock,Kenneth W. Mahaffey,Bruce Neal,Hiddo J.L. Heerspink,Hiddo J.L. Heerspink,Hiddo J.L. Heerspink +16 more
TLDR
To assess whether the effects of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors on cardiovascular, kidney and mortality outcomes are consistent with and without concomitant metformin use, a large number of patients were enrolled in a double-blind, placebo-controlled trial.Abstract:
Aim To assess whether the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors on cardiovascular, kidney and mortality outcomes are consistent with and without concomitant metformin use. Material and methods We conducted a meta-analysis of event-driven, randomized, placebo-controlled SGLT2 inhibitor trials that reported cardiovascular, kidney or mortality outcomes by baseline metformin use. Treatment effects, reported as hazards ratios (HRs) and 95% confidence intervals (CIs), were pooled using random-effects meta-analysis. The main outcomes in this analysis were (i) major adverse cardiovascular events (MACE) and (ii) hospitalization for heart failure (HHF) or cardiovascular death. Results We included six trials of four SGLT2 inhibitors that enrolled a total of 51 743 participants. Baseline metformin use varied from 21% in DAPA-HF to 82% in DECLARE-TIMI 58. SGLT2 inhibitors reduced the risk of MACE, with and without concomitant metformin use (HR 0.93, 95% CI 0.87-1.00 and HR 0.82, 95% CI 0.71-0.86, respectively; P-heterogeneity = 0.14). There were also clear and separate reductions in HHF or cardiovascular death with SGLT2 inhibitors, irrespective of metformin use (HR 0.79, 95% CI 0.73-0.86 and HR 0.74, 95% CI 0.63-0.87, respectively; P-heterogeneity = 0.48), as well as for major kidney outcomes and all-cause mortality (all P-heterogeneity > 0.40). Conclusion Treatment with SGLT2 inhibitors results in clear and consistent reductions in cardiovascular, kidney and mortality outcomes regardless of whether patients are receiving or not receiving metformin.read more
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2021 ESC Guidelines on cardiovascular disease prevention in clinical practice
Frank L.J. Visseren,François Mach,Yvo M. Smulders,David Carballo,Konstantinos C. Koskinas,Maria Bäck,Athanase Benetos,Alessandro Biffi,José-Manuel Boavida,Davide Capodanno,Bernard Cosyns,Carolyn Crawford,Constantinos H. Davos,Ileana Desormais,Emanuele Di Angelantonio,Oscar H. Franco,Sigrun Halvorsen,FD Richard Hobbs,Monika Hollander,Ewa A. Jankowska,Matthias Michal,Simona Sacco,Naveed Sattar,Lale Tokgozoglu,Serena Tonstad,Konstantinos P Tsioufis,Ineke van Dis,Isabelle C. Van Gelder,Christoph Wanner,Bryan Williams,Guy De Backer,Vera Regitz-Zagrosek,Anne Hege Aamodt,Magdy Abdelhamid,Victor Aboyans,Christian Albus,Riccardo Asteggiano,Magnus Bäck,Michael A. Borger,Carlos Brotons,Jelena Čelutkienė,Renata Cifkova,Maja Čikeš,Francesco Cosentino,Nikolaos Dagres,Tine De Backer,Dirk De Bacquer,Victoria Delgado,Hester Den Ruijter,Paul Dendale,Heinz Drexel,Volkmar Falk,Laurent Fauchier,Brian A. Ference,Jean Ferrières,Marc Ferrini,Miles Fisher,Danilo Fliser,Zlatko Fras,Dan Gaita,Simona Giampaoli,Stephan Gielen,Ian D. Graham,Catriona Jennings,Torben Jørgensen,Alexandra Kautzky-Willer,Maryam Kavousi,Wolfgang Koenig,Aleksandra Konradi,Dipak Kotecha,Ulf Landmesser,Madalena Lettino,Basil S. Lewis,Aleš Linhart,Maja-Lisa Løchen,Konstantinos Makrilakis,Giuseppe Mancia,Pedro Marques-Vidal,John W. McEvoy,Paul McGreavy,Béla Merkely,Lis Neubeck,Jens Cosedis Nielsen,Joep Perk,Steffen E. Petersen,Anna Sonia Petronio,Massimo F Piepoli,Nana Pogosova,Eva Prescott,Kausik K. Ray,Zeljko Reiner,Dimitrios J. Richter,Lars Rydén,Evgeny Shlyakhto,Marta Sitges,Miguel Sousa-Uva,Isabella Sudano,Monica Tiberi,Rhian M. Touyz,Andrea Ungar,W. M. Monique Verschuren,Olov Wiklund,David A. Wood,José Luis Zamorano,Carolyn A Crawford,Oscar H Franco Duran +105 more
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2016 ESC guidelines on cardiovascular disease prevention in clinical practice
Piepoli Adgdtmf.,Arno W. Hoes,Stefan Agewall,Christian Albus,Carlos Brotons,Alberico L. Catapano,Marie-Therese Cooney,Ugo Corrà,Bernard Cosyns,Christi Deaton,Ian D. Graham,Michael Stephen Hall,Hobbs Fdr.,Maja-Lisa Løchen,Herbert Löllgen,Pedro Marques-Vidal,Joep Perk,Eva Prescott,Josep Redon,Dimitrios J. Richter,Naveed Sattar,Y.M. Smulders,Monica Tiberi,H B van der Worp,I van Dis,Verschuren Wmm.,Binno Cas.,Backer Rddgd.,Marco Roffi,Victor Aboyans,Norbert Bachl,Héctor Bueno,Scipione Carerj,Leslie Cho,John Cox,Johan De Sutter,Günther Egidi,Miles Fisher,Donna Fitzsimons,Oscar H. Franco,Maxime Guenoun,C Jennings,Borut Jug,Paulus Kirchhof,Kornelia Kotseva,Lip Gyh.,François Mach,Giuseppe Mancia,Franz Martin Bermudo,Alessandro Mezzani,Alexander Niessner,Piotr Ponikowski,Bernhard Rauch,Lars Rydén,Adrienne Stauder,Guillaume Turc,Olov Wiklund,Stephan Windecker,José Luis Zamorano +58 more
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Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
Melanie J. Davies,Vanita R. Aroda,Billy S Collins,Robert A. Gabbay,Jennifer B. Green,Nisa M. Maruthur,Sylvia E. Rosas,Stefano Del Prato,Chantal Mathieu,Geltrude Mingrone,Peter Rossing,Tsvetalina Tankova,Apostolos Tsapas,John B. Buse +13 more
TL;DR: A panel to update the previous consensus statements on the management of hyperglycemia in type 2 diabetes in adults, published since 2006 and last updated in 2019, concludes that there is a greater emphasis on weight management as part of the holistic approach to diabetes management.
Journal ArticleDOI
Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
Melanie J. Davies,Vanita R. Aroda,Billy S Collins,Robert A. Gabbay,Jennifer B. Green,Nisa M. Maruthur,Sylvia E. Rosas,Stefano Del Prato,Chantal Mathieu,Geltrude Mingrone,Peter Rossing,Tsvetalina Tankova,Apostolos Tsapas,John B. Buse +13 more
TL;DR: The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the previous consensus statements on the management of hyperglycaemia in type 2 diabetes in adults, published since 2006 and last updated in 2019 as discussed by the authors .
Journal ArticleDOI
2021 ESC Guidelines on cardiovascular disease prevention in clinical practice
Frank L.J. Visseren,François Mach,Yvo M. Smulders,David Carballo,Konstantinos C. Koskinas,Maria Bäck,Athanase Benetos,Alessandro Biffi,José-Manuel Boavida,Davide Capodanno,Bernard Cosyns,Carolyn Crawford,Constantinos H. Davos,Ileana Desormais,Emanuele Di Angelantonio,Oscar H. Franco,Sigrun Halvorsen,FD Richard Hobbs,Monika Hollander,Ewa A. Jankowska,Matthias Michal,Simona Sacco,Naveed Sattar,Lale Tokgozoglu,Serena Tonstad,Konstantinos P Tsioufis,Ineke van Dis,Isabelle C. Van Gelder,Christoph Wanner,Bryan L. Williams +29 more
References
More filters
Journal ArticleDOI
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.
Bernard Zinman,Christoph Wanner,John M. Lachin,David Fitchett,Erich Bluhmki,Stefan Hantel,Michaela Mattheus,Theresa Devins,Odd Erik Johansen,Hans-Juergen Woerle,Uli C. Broedl,Silvio E. Inzucchi +11 more
TL;DR: Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care.
Journal Article
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)
R C Turner,Rury R. Holman,Irene M Stratton,Carole A. Cull,David R Matthews,Susan E. Manley,V Frighi,D Wright,Andrew Neil,E M Kohner,H McElroy,C Fox,D R Hadden,Grp Ukpds. +13 more
TL;DR: Since intensive glucose control with metformin appears to decrease the risk of diabetes-related endpoints in overweight diabetic patients, and is associated with less weight gain and fewer hypoglycaemic attacks than are insulin and sulphonylureas, it may be the first-line pharmacological therapy of choice in these patients.
Journal ArticleDOI
10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes
TL;DR: Despite an early loss of glycemic differences, a continued reduction in microvascular risk and emergent risk reductions for myocardial infarction and death from any cause were observed during 10 years of post-trial follow-up.
Journal ArticleDOI
Canagliflozin and cardiovascular and renal events in type 2 diabetes
Bruce Neal,Vlado Perkovic,Vlado Perkovic,Kenneth W. Mahaffey,Dick de Zeeuw,Greg Fulcher,Ngozi Erondu,Wayne Shaw,Gordon Law,Mehul Desai,David R. Matthews +10 more
TL;DR: Patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal.
Journal ArticleDOI
Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction
John J.V. McMurray,Scott D. Solomon,Silvio E. Inzucchi,Lars Køber,Mikhail Kosiborod,Felipe Martinez,Piotr Ponikowski,Marc S. Sabatine,Marc S. Sabatine,Inder S. Anand,Jan Bělohlávek,Michael Böhm,Chern-En Chiang,Chern-En Chiang,Vijay K. Chopra,Rudolf A. de Boer,Akshay S. Desai,Mirta Diez,Jarosław Drożdż,Andrej Dukát,Junbo Ge,Jonathan G. Howlett,Jonathan G. Howlett,Tzvetana Katova,Masafumi Kitakaze,Charlotta Ljungman,Béla Merkely,Jose C. Nicolau,Eileen O'Meara,Mark C. Petrie,Pham Nguyen Vinh,Morten Schou,Tereshchenko Sn,Subodh Verma,Claes Held,David L. DeMets,Kieran F. Docherty,Pardeep S. Jhund,Olof Bengtsson,Mikaela Sjöstrand,AM Langkilde +40 more
TL;DR: Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than amongThose who received placebo, regardless of the presence or absence of diabetes.
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