Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Endocrine
Published in: Endocrine 1/2019

01-07-2019 | Empagliflozin | Meta-Analysis

Type 2 diabetes and risk of heart failure: a systematic review and meta-analysis from cardiovascular outcome trials

Authors: Dario Giugliano, Maria Ida Maiorino, Miriam Longo, Giuseppe Bellastella, Paolo Chiodini, Katherine Esposito

Published in: Endocrine | Issue 1/2019

Login to get access

Abstract

Aim

We performed a meta-analysis of randomized controlled trials (RCTs) that evaluated the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium glucose co-transporter-2 inhibitors (SGLT-2i) on heart failure (HF) risk in patients with type 2 diabetes (T2D).

Methods and results

The electronic search was carried out until 10 November 2018. RCTs were included if they compared add-on therapy with any DPP-4i, GLP-1 RAs, or SGLT-2i with placebo, and included in the outcome hospitalization for HF, and other outcomes required for cardiovascular safety studies. Risk of HF was the primary outcome for this meta-analysis. We used a random-effect model to calculate hazard ratio (HR) and 95% CI. Twelve trials were identified, involving 120,765 patients. Compared with placebo, HF risk showed a non-significant 10% reduction with the newer anti-hyperglycemic drugs (HR = 0.90, 0.80–1.01); use of DPP-4i and GLP-1 RAs was associated with nonsignificant modifications of the HF risk (+5% and −9%, respectively), while the use of SGLT-2i was associated with a significant 31% reduction of the HF risk (HR = 0.69, 0.61–0.79, P < 0.001), with no heterogeneity (I2 = 0%, P = 0.741), suggesting a class effect. The meta-regression analysis of all 12 trials showed no association of reductions of hemoglobin A1C with HF risk.

Conclusion

In T2D, SGLT-2i can reduce the risk of HF that is unrelated to improved glycemic control; DPP-4i and GLP-1 RAs behave as neutral.
Appendix
Available only for authorised users
Literature
1.
P.M. Seferovi, M.C. Petrie, G.S. Filippatos, S.D. Anker, G. Rosano, J. Bauersachs, W.J. Paulus, M. Komajda, F. Cosentino, R.A. de Boer, D. Farmakis, W. Doehner, E. Lambrinou, Y. Lopatin, M.F. Piepoli, M.J. Theodorakis, H. Wiggers, Lekakis, A. Mebazaa, M.A. Mamas, C. Tschöpe, A.W. Hoes, J.P. Seferović, J. Logue, T. McDonagh, J.P. Riley, I. Milinković, M. Polovina, D.J. van Veldhuisen, M. Lainscak, A.P. Maggioni, F. Ruschitzka, J.J.V. McMurray, Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur. J. Heart Fail. 20, 853–872 (2018)CrossRef
2.
Y.J. Cheng, G. Imperatore, L.S. Geiss, S.H. Saydah, A.L. Albright, M.K. Ali, E.W. Gregg, Trends and disparities in cardiovascular mortality among U.S. adults with and without self-reported diabetes mellitus, 1988–2015. Diabetes Care 41, 2306–2315 (2018)CrossRefPubMed
3.
D. Giugliano, M.I. Maiorino, G. Bellastella, K. Esposito, Glycemic control in type 2 diabetes: from medication nonadherence to residual vascular risk. Endocrine 61, 23–27 (2018)CrossRefPubMed
4.
5.
C.K. Kramer, C. Ye, S. Campbell, R. Retnakaran, Comparison of new glucose-lowering drugs on risk of heart failure in type 2 diabetes. A network meta-analysis. JACC Heart Fail. 6, 823–830 (2018)CrossRefPubMed
6.
T.A. Zelniker, S.D. Wiviott, I. Raz, K. Im, E.L. Goodrich, M.P. Bonaca, O. Mosenzon, E.T. Kato, A. Cahn, R.H.M. Furtado, D.L. Bhatt, L.A. Leiter, D.K. McGuire, J.P.H. Wilding, M.S. Sabatine,, SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet 393(10166), 31–39 (2018)CrossRefPubMed
7.
M.I. Maiorino, P. Chiodini, G. Bellastella, L. Scappaticcio, M. Longo, K. Esposito, D. Giugliano, Free and fixed-ratio combinations of basal insulin and GLP-1 receptor agonists versus basal insulin intensification in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Obes. Metab. 20, 2309–2313 (2018)CrossRefPubMed
8.
M.I. Maiorino, P. Chiodini, G. Bellastella, A. Capuano, K. Esposito, D. Giugliano, Insulin and glucagon-like peptide 1 receptor agonist combination therapy in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Care 40, 614–624 (2017)CrossRefPubMed
9.
K. Esposito, P. Chiodini, A. Colao, A. Lenzi, D. Giugliano, Metabolic syndrome and risk of cancer: a systematic review and meta-analysis. Diabetes Care 35, 2402–2411 (2012)CrossRefPubMedPubMedCentral
10.
A. Liberati, D.G. Altman, J. Tetzlaff, C. Mulrow, P.C. Gøtzsche, J.P. Ioannidis, M. Clarke, P.J. Devereaux, J. Kleijnen, D. Moher, The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann. Intern. Med. 151, W65–W94 (2009)CrossRefPubMed
11.
J.P. Higgins, D.G. Altman, P.C. Gøtzsche, P. Jüni, D. Moher, A.D. Oxman, J. Savovic, K.F. Schulz, L. Weeks, J.A. Sterne; Cochrane Bias Methods Group; Cochrane Statistical Methods Group, The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. Br. Med. J. 343, d5928 (2011)CrossRef
12.
A.R. Jadad, R.A. Moore, D. Carroll, C. Jenkinson, D.J. Reynolds, D.J. Gavaghan, H.J. McQuay, Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin. Trials 17, 1–12 (1996)CrossRefPubMed
13.
M. Egger, G. Davey Smith, M. Schneider, C. Minder, Bias in meta-analysis detected by a simple, graphical test. Br. Med. J. 315, 629–634 (1997)CrossRef
14.
J.P. Higgins, S.G. Thompson, Controlling the risk of spurious findings from metaregression. Stat. Med. 23, 1663–1682 (2004)CrossRefPubMed
15.
B.M. Scirica, D.L. Bhatt, E. Braunwald, P.G. Steg, J. Davidson, B. Hirshberg, P. Ohman, R. Frederich, S.D. Wiviott, E.B. Hoffman, M.A. Cavender, J.A. Udell, N.R. Desai, O. Mosenzon, D.K. McGuire, K.K. Ray, L.A. Leiter, I. Raz; SAVOR-TIMI 53 Steering Committee and Investigators, Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N. Engl. J. Med. 369, 1317–1326 (2013)CrossRefPubMed
16.
W.B. White, C.P. Cannon, S.R. Heller, S.E. Nissen, R.M. Bergenstal, G.L. Bakris, A.T. Perez, P.R. Fleck, C.R. Mehta, S. Kupfer, C. Wilson, W.C. Cushman, F. Zannad; EXAMINE Investigators, Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N. Engl. J. Med. 369, 1327–1335 (2013)CrossRefPubMed
17.
J.B. Green, M.A. Bethel, P.W. Armstrong, J.B. Buse, S.S. Engel, J. Garg, R. Josse, K.D. Kaufman, J. Koglin, S. Korn, J.M. Lachin, D.K. McGuire, M.J. Pencina, E. Standl, P.P. Stein, S. Suryawanshi, F. Van de Werf, E.D. Peterson, R.R. Holman; TECOS Study Group, Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 373, 232–242 (2015)CrossRefPubMed
18.
J. Rosenstock, V. Perkovic, O.E. Johansen, M.E. Cooper, S.E. Kahn, N. Marx, J.H. Alexander, M. Pencina, R.D. Toto, C. Wanner, B. Zinman, H.J. Woerle, D. Baanstra, E. Pfarr, S. Schnaidt, T. Meinicke, J.T. George, M. von Eynatten, D.K. McGuire; CARMELINA Investigators, Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk. The CARMELINA randomized clinical trial. J. Am. Med. Assoc. 321, 69–79 (2019)
19.
M.A. Pfeffer, B. Claggett, R. Diaz, K. Dickstein, H.C. Gerstein, L.V. Køber, F.C. Lawson, L. Ping, X. Wei, E.F. Lewis, A.P. Maggioni, J.J. McMurray, J.L. Probstfield, M.C. Riddle, S.D. Solomon, J.C. Tardif; ELIXA Investigators, Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N. Engl. J. Med. 373, 2247–2257 (2015)CrossRefPubMed
20.
S.P. Marso, G.H. Daniels, K. Brown-Frandsen, P. Kristensen, J.F. Mann, M.A. Nauck, S.E. Nissen, S. Pocock, N.R. Poulter, L.S. Ravn, W.M. Steinberg, M. Stockner, B. Zinman, R.M. Bergenstal, J.B. Buse; LEADER Steering Committee; LEADER Trial Investigators, Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375, 311–322 (2016)CrossRefPubMedPubMedCentral
21.
S.P. Marso, S.C. Bain, A. Consoli, F.G. Eliaschewitz, E. Jódar, L.A. Leiter, I. Lingvay, J. Rosenstock, J. Seufert, M.L. Warren, V. Woo, O. Hansen, A.G. Holst, J. Pettersson, T. Vilsbøll; SUSTAIN-6 Investigators, Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 375, 1834–1844 (2016)CrossRefPubMed
22.
R.R. Holman, M.A. Bethel, R.J. Mentz, V.P. Thompson, Y. Lokhnygina, J.B. Buse, J.C. Chan, J. Choi, S.M. Gustavson, N. Iqbal, A.P. Maggioni, S.P. Marso, P. Öhman, N.J. Pagidipati, N. Poulter, A. Ramachandran, B. Zinman, A.F. Hernandez; EXSCEL Study Group, Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 377, 1228–1239 (2017)CrossRefPubMed
23.
A.F. Hernandez, J.B. Green, S. Janmohamed, R.B. D’Agostino Sr, C.B. Granger, N.P. Jones, L.A. Leiter, A.E. Rosenberg, K.N. Sigmon, M.C. Somerville, K.M. Thorpe, J.J.V. McMurray, S. Del Prato; Harmony Outcomes committees and investigators, Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet 392, 1519–1529 (2018)CrossRefPubMed
24.
B. Zinman, C. Wanner, J.M. Lachin, D. Fitchett, E. Bluhmki, S. Hantel, M. Mattheus, T. Devins, O.E. Johansen, H.J. Woerle, U.C. Broedl, S.E. Inzucchi; EMPA-REG OUTCOME Investigators, Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N. Engl. J. Med. 373, 2117–2128 (2015)CrossRefPubMed
25.
B. Neal, V. Perkovic, K.W. Mahaffey, D. de Zeeuw, G. Fulcher, N. Erondu, W. Shaw, G. Law, M. Desai, D.R. Matthews; CANVAS Program Collaborative Group, Canagliflozin and cardiovascular and renal events in type 2 diabetes. N. Engl. J. Med. 377, 644–657 (2017)CrossRefPubMed
26.
S.D. Wiviott, I. Raz, M.P. Bonaca, O. Mosenzon, E.T. Kato, A. Cahn, M.G. Silverman, T.A. Zelniker, J.F. Kuder, S.A. Murphy, D.L. Bhatt, L.A. Leiter, D.K. McGuire, J.P.H. Wilding, C.T. Ruff, I.A.M. Gause-Nilsson, M. Fredriksson, P.A. Johansson, A.-M. Langkilde, M.S. Sabatine; DECLARE–TIMI 58 Investigators, Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 380, 347–357 (2019)
27.
S. Verma, J.J.V. McMurray, SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia 61, 2108–2117 (2018)CrossRefPubMed
28.
D. Fitchett, B. Zinman, C. Wanner, J.M. Lachin, S. Hantel, A. Salsali, O.E. Johansen, H.J. Woerle, U.C. Broedl, S.E. Inzucchi; EMPA-REG OUTCOME® Trial Investigators, Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Eur. Heart J. 37, 1526–1534 (2016)CrossRefPubMedPubMedCentral
29.
K. Rådholm, G. Figtree, V. Perkovic, S.D. Solomon, K.W. Mahaffey, D. de Zeeuw, G. Fulcher, T.D. Barrett, W. Shaw, M. Desai, D.R. Matthews, B. Neal, Canagliflozin and heart failure in type 2 diabetes mellitus. Results from the CANVAS Program. Circulation 138, 458–468 (2018)CrossRefPubMedPubMedCentral
30.
M.J. Davies, D.A. D’Alessio, J. Fradkin, W.N. Kernan, C. Mathieu, G. Mingrone, P. Rossing, A. Tsapas, D.J. Wexler, J.B. Buse, Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 61, 2461–2498 (2018)CrossRefPubMed
31.
M. Kosiborod, M.A. Cavender, A.Z. Fu, A.Z. Fu, J.P. Wilding, K. Khunti, R.W. Holl, A. Norhammar, K.I. Birkeland, M.E. Jørgensen, M. Thuresson, N. Arya, J. Bodegård, N. Hammar, P. Fenici; CVD-REAL Investigators and Study Group, 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 136, 249–259 (2017)CrossRefPubMedPubMedCentral
32.
P.B. Ryan, J.B. Buse, M.J. Schuemie, F. DeFalco, Z. Yuan, P.E. Stang, J.A. Berlin, N. Rosenthal, Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: a real-world meta-analysis of 4 observational databases (OBSERVE-4D). Diabetes Obes. Metab. 20, 2585–2597 (2018)CrossRefPubMedPubMedCentral
33.
Metadata
Title
Type 2 diabetes and risk of heart failure: a systematic review and meta-analysis from cardiovascular outcome trials
Authors
Dario Giugliano
Maria Ida Maiorino
Miriam Longo
Giuseppe Bellastella
Paolo Chiodini
Katherine Esposito
Publication date
01-07-2019
Publisher
Springer US
Published in
Endocrine / Issue 1/2019
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-019-01931-y

Other articles of this Issue 1/2019

Endocrine 1/2019 Go to the issue

Letter to the Editor

Long-term control of Paget’s disease of bone with low-dose, once-weekly, oral bisphosphonate preparations, in a “real world” setting

Letter to the Editor

Reply to “Methodological issues in meta-analysis of the metformin effects on simple obesity”

Original Article

Birthweight correlates with later metabolic abnormalities in Chinese patients with maturity-onset diabetes of the young type 2

Original Article

Fractalkine: an inflammatory chemokine elevated in subjects with polycystic ovary syndrome

Meta-Analysis

Efficacy and safety of long-acting growth hormone in children with short stature: a systematic review and meta-analysis

Correction

Correction to: Absence of EIF1AX, PPM1D, and CHEK2 mutations reported in Thyroid Cancer Genome Atlas (TCGA) in a large series of thyroid cancer
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits