Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2021

Open Access 01-12-2021 | Heart Failure | Review

Effect of sodium–glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis

Authors: Yi-Wen Yu, Xue-Mei Zhao, Yun-Hong Wang, Qiong Zhou, Yan Huang, Mei Zhai, Jian Zhang

Published in: Cardiovascular Diabetology | Issue 1/2021

Login to get access

Abstract

Background

Although the benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular events have been reported in patients with type 2 diabetes mellitus (T2DM) with or without heart failure (HF), the impact of SGLT2i on cardiac remodelling remains to be established.

Methods

We searched the PubMed, Embase, Cochrane Library and Web of Science databases up to November 16th, 2020, for randomized controlled trials reporting the effects of SGLT2i on parameters of cardiac structure, cardiac function, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level or the Kansas City Cardiomyopathy Questionnaire (KCCQ) score in T2DM patients with or without chronic HF. The effect size was expressed as the mean difference (MD) or standardized mean difference (SMD) and its 95% confidence interval (CI). Subgroup analyses were performed based on the stage A–B or stage C HF population and HF types.

Results

Compared to placebo or other antidiabetic drugs, SGLT2i showed no significant effects on left ventricular mass index, left ventricular end diastolic volume index, left ventricular end systolic volume index, or left atrial volume index. SGLT2i improved left ventricular ejection fraction only in the subgroup of HF patients with reduced ejection fraction (MD 3.16%, 95% CI 0.11 to 6.22, p = 0.04; I2 = 0%), and did not affect the global longitudinal strain in the overall analysis including stage A–B HF patients. SGLT2i showed benefits in the E/e’ ratio (MD − 0.45, 95% CI − 0.88 to − 0.03, p = 0.04; I2 = 0%), plasma NT-proBNP level (SMD − 0.09, 95% CI − 0.16 to − 0.03, p = 0.004; I2 = 0%), and the KCCQ score (SMD 3.12, 95% CI 0.76 to 5.47, p  = 0.01; I2 = 0%) in the overall population.

Conclusion

The use of SGLT2i was associated with significant improvements in cardiac diastolic function, plasma NT-proBNP level, and the KCCQ score in T2DM patients with or without chronic HF, but did not significantly affect cardiac structural parameters indexed by body surface area. The LVEF level was improved only in HF patients with reduced ejection fraction.
Appendix
Available only for authorised users
Literature
1.
2.
go back to reference Dei Cas A, Khan SS, Butler J, Mentz RJ, Bonow RO, Avogaro A, et al. Impact of diabetes on epidemiology, treatment, and outcomes of patients with heart failure. JACC Heart Fail. 2015;3(2):136–45.PubMedCrossRef Dei Cas A, Khan SS, Butler J, Mentz RJ, Bonow RO, Avogaro A, et al. Impact of diabetes on epidemiology, treatment, and outcomes of patients with heart failure. JACC Heart Fail. 2015;3(2):136–45.PubMedCrossRef
3.
go back to reference McHugh K, DeVore AD, Wu J, Matsouaka RA, Fonarow GC, Heidenreich PA, et al. Heart failure with preserved ejection fraction and diabetes: JACC State-of-the-Art review. J Am Coll Cardiol. 2019;73(5):602–11.PubMedCrossRef McHugh K, DeVore AD, Wu J, Matsouaka RA, Fonarow GC, Heidenreich PA, et al. Heart failure with preserved ejection fraction and diabetes: JACC State-of-the-Art review. J Am Coll Cardiol. 2019;73(5):602–11.PubMedCrossRef
4.
go back to reference MacDonald MR, Petrie MC, Varyani F, Ostergren J, Michelson EL, Young JB, et al. Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J. 2008;29(11):1377–85.PubMedCrossRef MacDonald MR, Petrie MC, Varyani F, Ostergren J, Michelson EL, Young JB, et al. Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J. 2008;29(11):1377–85.PubMedCrossRef
5.
go back to reference Dauriz M, Mantovani A, Bonapace S, Verlato G, Zoppini G, Bonora E, et al. Prognostic impact of diabetes on long-term survival outcomes in patients with heart failure: a meta-analysis. Diabetes Care. 2017;40(11):1597–605.PubMedCrossRef Dauriz M, Mantovani A, Bonapace S, Verlato G, Zoppini G, Bonora E, et al. Prognostic impact of diabetes on long-term survival outcomes in patients with heart failure: a meta-analysis. Diabetes Care. 2017;40(11):1597–605.PubMedCrossRef
6.
go back to reference Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.PubMedCrossRef Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.PubMedCrossRef
7.
go back to reference Neal B, Perkovic V, Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(21):2099.PubMed Neal B, Perkovic V, Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(21):2099.PubMed
8.
go back to reference Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347–57.PubMedCrossRef Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347–57.PubMedCrossRef
9.
go back to reference Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, et al. 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. 2019;393(10166):31–9.CrossRefPubMed Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, et al. 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. 2019;393(10166):31–9.CrossRefPubMed
10.
go back to reference Petrie MC, Verma S, Docherty KF, Inzucchi SE, Anand I, Belohlavek J, et al. Effect of dapagliflozin on worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes. JAMA. 2020;323:1353–68.PubMedPubMedCentralCrossRef Petrie MC, Verma S, Docherty KF, Inzucchi SE, Anand I, Belohlavek J, et al. Effect of dapagliflozin on worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes. JAMA. 2020;323:1353–68.PubMedPubMedCentralCrossRef
11.
go back to reference Zhu J, Yu X, Zheng Y, Li J, Wang Y, Lin Y, et al. Association of glucose-lowering medications with cardiovascular outcomes: an umbrella review and evidence map. Lancet Diabetes Endocrinol. 2020;8(3):192–205.PubMedCrossRef Zhu J, Yu X, Zheng Y, Li J, Wang Y, Lin Y, et al. Association of glucose-lowering medications with cardiovascular outcomes: an umbrella review and evidence map. Lancet Diabetes Endocrinol. 2020;8(3):192–205.PubMedCrossRef
12.
go back to reference Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet (London, England). 2020;396(10254):819–29.CrossRef Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet (London, England). 2020;396(10254):819–29.CrossRef
13.
go back to reference Buse JB, Wexler DJ, Tsapas A, Rossing P, Mingrone G, Mathieu C, et al. 2019 Update to: 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). Diabetes Care. 2020;43(2):487–93.PubMedCrossRef Buse JB, Wexler DJ, Tsapas A, Rossing P, Mingrone G, Mathieu C, et al. 2019 Update to: 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). Diabetes Care. 2020;43(2):487–93.PubMedCrossRef
14.
go back to reference Seferovic PM, Coats AJS, Ponikowski P, Filippatos G, Huelsmann M, Jhund PS, et al. European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose-lowering drugs in patients with heart failure. Eur J Heart Fail. 2020;22(2):196–213.PubMedCrossRef Seferovic PM, Coats AJS, Ponikowski P, Filippatos G, Huelsmann M, Jhund PS, et al. European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose-lowering drugs in patients with heart failure. Eur J Heart Fail. 2020;22(2):196–213.PubMedCrossRef
15.
go back to reference Li CG, Zhang J, Xue M, Li XY, Han F, Liu XY, et al. SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart. Cardiovasc Diabetol. 2019;18:15.PubMedPubMedCentralCrossRef Li CG, Zhang J, Xue M, Li XY, Han F, Liu XY, et al. SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart. Cardiovasc Diabetol. 2019;18:15.PubMedPubMedCentralCrossRef
16.
go back to reference Lee TI, Chen YC, Lin YK, Chung CC, Lu YY, Kao YH, et al. Empagliflozin attenuates myocardial sodium and calcium dysregulation and reverses cardiac remodeling in streptozotocin-induced diabetic rats. Int J Mol Sci. 2019;20(7):1680.PubMedCentralCrossRef Lee TI, Chen YC, Lin YK, Chung CC, Lu YY, Kao YH, et al. Empagliflozin attenuates myocardial sodium and calcium dysregulation and reverses cardiac remodeling in streptozotocin-induced diabetic rats. Int J Mol Sci. 2019;20(7):1680.PubMedCentralCrossRef
17.
go back to reference Habibi J, Aroor AR, Sowers JR, Jia G, Hayden MR, Garro M, et al. Sodium glucose transporter 2 (SGLT2) inhibition with empagliflozin improves cardiac diastolic function in a female rodent model of diabetes. Cardiovasc Diabetol. 2017;16(1):9.PubMedPubMedCentralCrossRef Habibi J, Aroor AR, Sowers JR, Jia G, Hayden MR, Garro M, et al. Sodium glucose transporter 2 (SGLT2) inhibition with empagliflozin improves cardiac diastolic function in a female rodent model of diabetes. Cardiovasc Diabetol. 2017;16(1):9.PubMedPubMedCentralCrossRef
18.
go back to reference Yurista SR, Sillje HHW, Oberdorf-Maass SU, Schouten EM, Giani MGP, Hillebrands JL, et al. Sodium-glucose co-transporter 2 inhibition with empagliflozin improves cardiac function in non-diabetic rats with left ventricular dysfunction after myocardial infarction. Eur J Heart Fail. 2019;21(7):862–73.PubMedCrossRef Yurista SR, Sillje HHW, Oberdorf-Maass SU, Schouten EM, Giani MGP, Hillebrands JL, et al. Sodium-glucose co-transporter 2 inhibition with empagliflozin improves cardiac function in non-diabetic rats with left ventricular dysfunction after myocardial infarction. Eur J Heart Fail. 2019;21(7):862–73.PubMedCrossRef
19.
go back to reference Santos-Gallego CG, Requena-Ibanez JA, Antonio RS, Ishikawa K, Watanabe S, Picatoste B, et al. Empagliflozin ameliorates adverse left ventricular remodeling in nondiabetic heart failure by enhancing myocardial energetics. J Am Coll Cardiol. 2019;73(15):1931–44.PubMedCrossRef Santos-Gallego CG, Requena-Ibanez JA, Antonio RS, Ishikawa K, Watanabe S, Picatoste B, et al. Empagliflozin ameliorates adverse left ventricular remodeling in nondiabetic heart failure by enhancing myocardial energetics. J Am Coll Cardiol. 2019;73(15):1931–44.PubMedCrossRef
20.
go back to reference Byrne NJ, Parajuli N, Levasseur JL, Boisvenue J, Beker DL, Masson G, et al. Empagliflozin prevents worsening of cardiac function in an experimental model of pressure overload-induced heart failure. JACC Basic Transl Sci. 2017;2(4):347–54.PubMedPubMedCentralCrossRef Byrne NJ, Parajuli N, Levasseur JL, Boisvenue J, Beker DL, Masson G, et al. Empagliflozin prevents worsening of cardiac function in an experimental model of pressure overload-induced heart failure. JACC Basic Transl Sci. 2017;2(4):347–54.PubMedPubMedCentralCrossRef
21.
go back to reference Connelly KA, Zhang Y, Desjardins JF, Nghiem L, Visram A, Batchu SN, et al. Load-independent effects of empagliflozin contribute to improved cardiac function in experimental heart failure with reduced ejection fraction. Cardiovasc Diabetol. 2020;19(1):13.PubMedPubMedCentralCrossRef Connelly KA, Zhang Y, Desjardins JF, Nghiem L, Visram A, Batchu SN, et al. Load-independent effects of empagliflozin contribute to improved cardiac function in experimental heart failure with reduced ejection fraction. Cardiovasc Diabetol. 2020;19(1):13.PubMedPubMedCentralCrossRef
22.
go back to reference Connelly KA, Zhang Y, Visram A, Advani A, Batchu SN, Desjardins JF, et al. Empagliflozin improves diastolic function in a nondiabetic rodent model of heart failure with preserved ejection fraction. JACC Basic Transl Sci. 2019;4(1):27–37.PubMedPubMedCentralCrossRef Connelly KA, Zhang Y, Visram A, Advani A, Batchu SN, Desjardins JF, et al. Empagliflozin improves diastolic function in a nondiabetic rodent model of heart failure with preserved ejection fraction. JACC Basic Transl Sci. 2019;4(1):27–37.PubMedPubMedCentralCrossRef
23.
go back to reference Pabel S, Bollenberg H, Bengel P, Tirilomis P, Mustroph J, Wagner S, et al. Empagliflozin directly improves diastolic function in human heart failure. Eur Heart J. 2018;39:284–5.CrossRef Pabel S, Bollenberg H, Bengel P, Tirilomis P, Mustroph J, Wagner S, et al. Empagliflozin directly improves diastolic function in human heart failure. Eur Heart J. 2018;39:284–5.CrossRef
24.
go back to reference Brown AJM, Gandy S, McCrimmon R, Houston JG, Struthers AD, Lang CC. A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: the DAPA-LVH trial. Eur Heart J. 2020;41:3421–32.PubMedCrossRefPubMedCentral Brown AJM, Gandy S, McCrimmon R, Houston JG, Struthers AD, Lang CC. A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: the DAPA-LVH trial. Eur Heart J. 2020;41:3421–32.PubMedCrossRefPubMedCentral
25.
go back to reference Verma S, Mazer CD, Yan AT, Mason T, Garg V, Teoh H, et al. Effect of empagliflozin on left ventricular mass in patients with type 2 diabetes and coronary artery disease: the EMPA-HEART CardioLink-6 randomized clinical trial. Circulation. 2019;140:1693–702.PubMedCrossRef Verma S, Mazer CD, Yan AT, Mason T, Garg V, Teoh H, et al. Effect of empagliflozin on left ventricular mass in patients with type 2 diabetes and coronary artery disease: the EMPA-HEART CardioLink-6 randomized clinical trial. Circulation. 2019;140:1693–702.PubMedCrossRef
26.
go back to reference Braha A, Timar B, Diaconu L, Lupusoru R, Vasiluta L, Sima A, et al. Dynamics of epicardiac fat and heart function in type 2 diabetic patients initiated with SGLT-2 inhibitors. Diabetes Metab Syndr Obes Targets Ther. 2019;12:2559–66.CrossRef Braha A, Timar B, Diaconu L, Lupusoru R, Vasiluta L, Sima A, et al. Dynamics of epicardiac fat and heart function in type 2 diabetic patients initiated with SGLT-2 inhibitors. Diabetes Metab Syndr Obes Targets Ther. 2019;12:2559–66.CrossRef
27.
go back to reference Hwang IC, Cho GY, Yoon YE, Park JJ, Park JB, Lee SP, et al. Different effects of SGLT2 inhibitors according to the presence and types of heart failure in type 2 diabetic patients. Cardiovasc Diabetol. 2020;19(1):69.PubMedPubMedCentralCrossRef Hwang IC, Cho GY, Yoon YE, Park JJ, Park JB, Lee SP, et al. Different effects of SGLT2 inhibitors according to the presence and types of heart failure in type 2 diabetic patients. Cardiovasc Diabetol. 2020;19(1):69.PubMedPubMedCentralCrossRef
28.
go back to reference Matsutani D, Sakamoto M, Kayama Y, Takeda N, Horiuchi R, Utsunomiya K. Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes. Cardiovasc Diabetol. 2018;17(1):73.PubMedPubMedCentralCrossRef Matsutani D, Sakamoto M, Kayama Y, Takeda N, Horiuchi R, Utsunomiya K. Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes. Cardiovasc Diabetol. 2018;17(1):73.PubMedPubMedCentralCrossRef
29.
go back to reference Singh JSS, Mordi IR, Vickneson K, Fathi A, Donnan PT, Mohan M, et al. Dapagliflozin versus placebo on left ventricular remodeling in patients with diabetes and heart failure: the REFORM trial. Diabetes Care. 2020;43:1356–9.PubMedPubMedCentralCrossRef Singh JSS, Mordi IR, Vickneson K, Fathi A, Donnan PT, Mohan M, et al. Dapagliflozin versus placebo on left ventricular remodeling in patients with diabetes and heart failure: the REFORM trial. Diabetes Care. 2020;43:1356–9.PubMedPubMedCentralCrossRef
30.
go back to reference Carbone S, Billingsley HE, Canada JM, Bressi E, Rotelli B, Kadariya D, et al. The effects of canagliflozin compared to sitagliptin on cardiorespiratory fitness in type 2 diabetes mellitus and heart failure with reduced ejection fraction: results of the CANA-HF study. Diabetes/metabolism research and reviews. 2020;36:e3335.PubMedPubMedCentralCrossRef Carbone S, Billingsley HE, Canada JM, Bressi E, Rotelli B, Kadariya D, et al. The effects of canagliflozin compared to sitagliptin on cardiorespiratory fitness in type 2 diabetes mellitus and heart failure with reduced ejection fraction: results of the CANA-HF study. Diabetes/metabolism research and reviews. 2020;36:e3335.PubMedPubMedCentralCrossRef
31.
go back to reference Tanaka A, Hisauchi I, Taguchi I, Sezai A, Toyoda S, Tomiyama H, et al. Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE). ESC heart failure. 2020;7:1585–94.PubMedPubMedCentralCrossRef Tanaka A, Hisauchi I, Taguchi I, Sezai A, Toyoda S, Tomiyama H, et al. Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE). ESC heart failure. 2020;7:1585–94.PubMedPubMedCentralCrossRef
32.
go back to reference McMurray JJV, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995–2008.PubMedCrossRef McMurray JJV, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995–2008.PubMedCrossRef
33.
go back to reference de Boer RA, Nunez J, Kozlovski P, Wang Y, Proot P, Keefe D. Effects of the dual sodium-glucose linked transporter inhibitor, licogliflozinvsplacebo or empagliflozin in patients with type 2 diabetes and heart failure. Br J Clin Pharmacol. 2020;86(7):1346–56.PubMedPubMedCentralCrossRef de Boer RA, Nunez J, Kozlovski P, Wang Y, Proot P, Keefe D. Effects of the dual sodium-glucose linked transporter inhibitor, licogliflozinvsplacebo or empagliflozin in patients with type 2 diabetes and heart failure. Br J Clin Pharmacol. 2020;86(7):1346–56.PubMedPubMedCentralCrossRef
34.
go back to reference Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1.PubMedPubMedCentralCrossRef Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1.PubMedPubMedCentralCrossRef
36.
go back to reference Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.PubMedPubMedCentralCrossRef Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.PubMedPubMedCentralCrossRef
38.
go back to reference Higgins JP, White IR, Anzures-Cabrera J. Meta-analysis of skewed data: combining results reported on log-transformed or raw scales. Stat Med. 2008;27(29):6072–92.PubMedPubMedCentralCrossRef Higgins JP, White IR, Anzures-Cabrera J. Meta-analysis of skewed data: combining results reported on log-transformed or raw scales. Stat Med. 2008;27(29):6072–92.PubMedPubMedCentralCrossRef
39.
go back to reference Ikonomidis I, Pavlidis G, Thymis J, Birba D, Kalogeris A, Kousathana F, et al. Effects of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and their combination on endothelial glycocalyx, arterial function, and myocardial work index in patients with type 2 diabetes mellitus after 12-month treatment. J Am Heart Assoc. 2020;9(9):e015716.PubMedPubMedCentralCrossRef Ikonomidis I, Pavlidis G, Thymis J, Birba D, Kalogeris A, Kousathana F, et al. Effects of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and their combination on endothelial glycocalyx, arterial function, and myocardial work index in patients with type 2 diabetes mellitus after 12-month treatment. J Am Heart Assoc. 2020;9(9):e015716.PubMedPubMedCentralCrossRef
40.
go back to reference Bonora BM, de Kreutzenberg SV, Avogaro A, Fadini GP. Effects of the SGLT2 inhibitor dapagliflozin on cardiac function evaluated by impedance cardiography in patients with type 2 diabetes Secondary analysis of a randomized placebo-controlled trial. Cardiovasc Diabetol. 2019;18(1):106.PubMedPubMedCentralCrossRef Bonora BM, de Kreutzenberg SV, Avogaro A, Fadini GP. Effects of the SGLT2 inhibitor dapagliflozin on cardiac function evaluated by impedance cardiography in patients with type 2 diabetes Secondary analysis of a randomized placebo-controlled trial. Cardiovasc Diabetol. 2019;18(1):106.PubMedPubMedCentralCrossRef
41.
go back to reference Griffin M, Rao VS, Ivey-Miranda J, Fleming J, Mahoney D, Maulion C, et al. Empagliflozin in heart failure: diuretic and cardio-renal effects. Circulation. 2020;142:1028–39.PubMedCrossRefPubMedCentral Griffin M, Rao VS, Ivey-Miranda J, Fleming J, Mahoney D, Maulion C, et al. Empagliflozin in heart failure: diuretic and cardio-renal effects. Circulation. 2020;142:1028–39.PubMedCrossRefPubMedCentral
43.
go back to reference Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2020. https://doi.org/10.1056/NEJMoa2030183. Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2020. https://​doi.​org/​10.​1056/​NEJMoa2030183.​
44.
go back to reference Eickhoff MK, Olsen FJ, Frimodt-Moller M, Diaz LJ, Faber J, Jensen MT, et al. Effect of dapagliflozin on cardiac function in people with type 2 diabetes and albuminuria—a double blind randomized placebo-controlled crossover trial. J Diabetes Complications. 2020;34(7):107590.PubMedCrossRef Eickhoff MK, Olsen FJ, Frimodt-Moller M, Diaz LJ, Faber J, Jensen MT, et al. Effect of dapagliflozin on cardiac function in people with type 2 diabetes and albuminuria—a double blind randomized placebo-controlled crossover trial. J Diabetes Complications. 2020;34(7):107590.PubMedCrossRef
45.
go back to reference Ejiri K, Miyoshi T, Kihara H, Hata Y, Nagano T, Takaishi A, et al. Effect of luseogliflozin on heart failure with preserved ejection fraction in patients with diabetes mellitus. J Am Heart Assoc. 2020;9(16):e015103.PubMedPubMedCentralCrossRef Ejiri K, Miyoshi T, Kihara H, Hata Y, Nagano T, Takaishi A, et al. Effect of luseogliflozin on heart failure with preserved ejection fraction in patients with diabetes mellitus. J Am Heart Assoc. 2020;9(16):e015103.PubMedPubMedCentralCrossRef
46.
go back to reference Januzzi JL Jr, Butler J, Jarolim P, Sattar N, Vijapurkar U, Desai M, et al. Effects of canagliflozin on cardiovascular biomarkers in older adults with type 2 diabetes. J Am Coll Cardiol. 2017;70(6):704–12.PubMedCrossRef Januzzi JL Jr, Butler J, Jarolim P, Sattar N, Vijapurkar U, Desai M, et al. Effects of canagliflozin on cardiovascular biomarkers in older adults with type 2 diabetes. J Am Coll Cardiol. 2017;70(6):704–12.PubMedCrossRef
47.
go back to reference Januzzi JL Jr, Xu J, Li J, Shaw W, Oh R, Pfeifer M, et al. Effects of canagliflozin on amino-terminal pro-b-type natriuretic peptide: implications for cardiovascular risk reduction. J Am Coll Cardiol. 2020;76(18):2076–85.PubMedCrossRef Januzzi JL Jr, Xu J, Li J, Shaw W, Oh R, Pfeifer M, et al. Effects of canagliflozin on amino-terminal pro-b-type natriuretic peptide: implications for cardiovascular risk reduction. J Am Coll Cardiol. 2020;76(18):2076–85.PubMedCrossRef
48.
go back to reference Katakami N, Mita T, Yoshii H, Shiraiwa T, Yasuda T, Okada Y, et al. Tofogliflozin does not delay progression of carotid atherosclerosis in patients with type 2 diabetes: a prospective, randomized, open-label, parallel-group comparative study. Cardiovasc Diabetol. 2020;19(1):1–16.CrossRef Katakami N, Mita T, Yoshii H, Shiraiwa T, Yasuda T, Okada Y, et al. Tofogliflozin does not delay progression of carotid atherosclerosis in patients with type 2 diabetes: a prospective, randomized, open-label, parallel-group comparative study. Cardiovasc Diabetol. 2020;19(1):1–16.CrossRef
49.
go back to reference Kayano H, Koba S, Hirano T, Matsui T, Fukuoka H, Tsuijita H, et al. Dapagliflozin influences ventricular hemodynamics and exercise-induced pulmonary hypertension in type 2 diabetes patients—a randomized controlled trial. Circ J. 2020;84(10):1807–17.PubMedCrossRef Kayano H, Koba S, Hirano T, Matsui T, Fukuoka H, Tsuijita H, et al. Dapagliflozin influences ventricular hemodynamics and exercise-induced pulmonary hypertension in type 2 diabetes patients—a randomized controlled trial. Circ J. 2020;84(10):1807–17.PubMedCrossRef
50.
go back to reference Mordi NA, Mordi IR, Singh JS, McCrimmon RJ, Struthers AD, Lang CC. Renal and cardiovascular effects of SGLT2 inhibition in combination with loop diuretics in patients with type 2 diabetes and chronic heart failure: the recede-chf trial. Circulation. 2020;142(18):1713–24.PubMedPubMedCentralCrossRef Mordi NA, Mordi IR, Singh JS, McCrimmon RJ, Struthers AD, Lang CC. Renal and cardiovascular effects of SGLT2 inhibition in combination with loop diuretics in patients with type 2 diabetes and chronic heart failure: the recede-chf trial. Circulation. 2020;142(18):1713–24.PubMedPubMedCentralCrossRef
51.
go back to reference Oldgren J, Laurila S, Akerblom A, Latva-Rasku A, Rebelos E, Isackson H, et al. Effects of 6 weeks of treatment with dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes. Diabetologia. 2020;63(SUPPL 1):S62–3. Oldgren J, Laurila S, Akerblom A, Latva-Rasku A, Rebelos E, Isackson H, et al. Effects of 6 weeks of treatment with dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes. Diabetologia. 2020;63(SUPPL 1):S62–3.
53.
go back to reference Patoulias D, Papadopoulos C, Katsimardou A, Kalogirou M-S, Doumas M. Meta-analysis assessing the effect of sodium-glucose co-transporter-2 inhibitors on left ventricular mass in patients with type 2 diabetes mellitus. Am J Cardiol. 2020;134:149–52.PubMedCrossRef Patoulias D, Papadopoulos C, Katsimardou A, Kalogirou M-S, Doumas M. Meta-analysis assessing the effect of sodium-glucose co-transporter-2 inhibitors on left ventricular mass in patients with type 2 diabetes mellitus. Am J Cardiol. 2020;134:149–52.PubMedCrossRef
54.
go back to reference Storgaard H, Gluud LL, Bennett C, Grøndahl MF, Christensen MB, Knop FK, et al. Benefits and harms of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and meta-analysis. PLoS ONE. 2016;11(11):e0166125.PubMedPubMedCentralCrossRef Storgaard H, Gluud LL, Bennett C, Grøndahl MF, Christensen MB, Knop FK, et al. Benefits and harms of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and meta-analysis. PLoS ONE. 2016;11(11):e0166125.PubMedPubMedCentralCrossRef
55.
go back to reference Drazner MH, Rame JE, Marino EK, Gottdiener JS, Kitzman DW, Gardin JM, et al. Increased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years: the Cardiovascular Health Study. J Am Coll Cardiol. 2004;43(12):2207–15.PubMedCrossRef Drazner MH, Rame JE, Marino EK, Gottdiener JS, Kitzman DW, Gardin JM, et al. Increased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years: the Cardiovascular Health Study. J Am Coll Cardiol. 2004;43(12):2207–15.PubMedCrossRef
56.
go back to reference Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;322(22):1561–6.PubMedCrossRef Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;322(22):1561–6.PubMedCrossRef
57.
go back to reference Sengeløv M, Jørgensen PG, Jensen JS, Bruun NE, Olsen FJ, Fritz-Hansen T, et al. Global longitudinal strain is a superior predictor of all-cause mortality in heart failure with reduced ejection fraction. JACC Cardiovasc Imaging. 2015;8(12):1351–9.PubMedCrossRef Sengeløv M, Jørgensen PG, Jensen JS, Bruun NE, Olsen FJ, Fritz-Hansen T, et al. Global longitudinal strain is a superior predictor of all-cause mortality in heart failure with reduced ejection fraction. JACC Cardiovasc Imaging. 2015;8(12):1351–9.PubMedCrossRef
58.
go back to reference Kraigher-Krainer E, Shah AM, Gupta DK, Santos A, Claggett B, Pieske B, et al. Impaired systolic function by strain imaging in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2014;63(5):447–56.PubMedCrossRef Kraigher-Krainer E, Shah AM, Gupta DK, Santos A, Claggett B, Pieske B, et al. Impaired systolic function by strain imaging in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2014;63(5):447–56.PubMedCrossRef
59.
go back to reference Liu JH, Chen Y, Yuen M, Zhen Z, Chan CW, Lam KS, et al. Incremental prognostic value of global longitudinal strain in patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2016;15:22.PubMedPubMedCentralCrossRef Liu JH, Chen Y, Yuen M, Zhen Z, Chan CW, Lam KS, et al. Incremental prognostic value of global longitudinal strain in patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2016;15:22.PubMedPubMedCentralCrossRef
60.
go back to reference Velazquez EJ, Reinhardt SW. Limitations of natriuretic peptide levels in establishing SGLT-2 inhibitors for heart failure care. J Am Coll Cardiol. 2020;76(18):2086–8.PubMedCrossRef Velazquez EJ, Reinhardt SW. Limitations of natriuretic peptide levels in establishing SGLT-2 inhibitors for heart failure care. J Am Coll Cardiol. 2020;76(18):2086–8.PubMedCrossRef
61.
go back to reference Savarese G, Musella F, D’Amore C, Vassallo E, Losco T, Gambardella F, et al. Changes of natriuretic peptides predict hospital admissions in patients with chronic heart failure: a meta-analysis. JACC Heart failure. 2014;2(2):148–58.PubMedCrossRef Savarese G, Musella F, D’Amore C, Vassallo E, Losco T, Gambardella F, et al. Changes of natriuretic peptides predict hospital admissions in patients with chronic heart failure: a meta-analysis. JACC Heart failure. 2014;2(2):148–58.PubMedCrossRef
62.
go back to reference Zile MR, Claggett BL, Prescott MF, McMurray JJ, Packer M, Rouleau JL, et al. Prognostic implications of changes in n-terminal pro-b-type natriuretic peptide in patients with heart failure. J Am Coll Cardiol. 2016;68(22):2425–36.PubMedCrossRef Zile MR, Claggett BL, Prescott MF, McMurray JJ, Packer M, Rouleau JL, et al. Prognostic implications of changes in n-terminal pro-b-type natriuretic peptide in patients with heart failure. J Am Coll Cardiol. 2016;68(22):2425–36.PubMedCrossRef
63.
go back to reference Cunningham JW, Vaduganathan M, Claggett BL, Zile MR, Anand IS, Packer M, et al. Effects of sacubitril/valsartan on N-terminal Pro-B-type natriuretic peptide in heart failure with preserved ejection fraction. JACC Heart Fail. 2020;8(5):372–81.PubMedCrossRef Cunningham JW, Vaduganathan M, Claggett BL, Zile MR, Anand IS, Packer M, et al. Effects of sacubitril/valsartan on N-terminal Pro-B-type natriuretic peptide in heart failure with preserved ejection fraction. JACC Heart Fail. 2020;8(5):372–81.PubMedCrossRef
64.
go back to reference Felker GM, Anstrom KJ, Adams KF, Ezekowitz JA, Fiuzat M, Houston-Miller N, et al. Effect of natriuretic peptide-guided therapy on hospitalization or cardiovascular mortality in high-risk patients with heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2017;318(8):713–20.PubMedPubMedCentralCrossRef Felker GM, Anstrom KJ, Adams KF, Ezekowitz JA, Fiuzat M, Houston-Miller N, et al. Effect of natriuretic peptide-guided therapy on hospitalization or cardiovascular mortality in high-risk patients with heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2017;318(8):713–20.PubMedPubMedCentralCrossRef
65.
go back to reference Spertus JA, Jones PG, Sandhu AT, Arnold SV. Interpreting the Kansas city cardiomyopathy questionnaire in clinical trials and clinical care: JACC state-of-the-art Review. J Am Coll Cardiol. 2020;76(20):2379–90.PubMedCrossRef Spertus JA, Jones PG, Sandhu AT, Arnold SV. Interpreting the Kansas city cardiomyopathy questionnaire in clinical trials and clinical care: JACC state-of-the-art Review. J Am Coll Cardiol. 2020;76(20):2379–90.PubMedCrossRef
66.
go back to reference Garg V, Verma S, Connelly K. Mechanistic insights regarding the role of SGLT2 inhibitors and GLP1 agonist drugs on cardiovascular disease in diabetes. Prog Cardiovasc Dis. 2019;62(4):349–57.PubMedCrossRef Garg V, Verma S, Connelly K. Mechanistic insights regarding the role of SGLT2 inhibitors and GLP1 agonist drugs on cardiovascular disease in diabetes. Prog Cardiovasc Dis. 2019;62(4):349–57.PubMedCrossRef
67.
go back to reference Striepe K, Jumar A, Ott C, Karg MV, Schneider MP, Kannenkeril D, et al. Effects of the selective sodium-glucose cotransporter 2 inhibitor empagliflozin on vascular function and central hemodynamics in patients with type 2 diabetes mellitus. Circulation. 2017;136(12):1167–9.PubMedCrossRef Striepe K, Jumar A, Ott C, Karg MV, Schneider MP, Kannenkeril D, et al. Effects of the selective sodium-glucose cotransporter 2 inhibitor empagliflozin on vascular function and central hemodynamics in patients with type 2 diabetes mellitus. Circulation. 2017;136(12):1167–9.PubMedCrossRef
68.
go back to reference Ferrannini E, Mark M, Mayoux E. CV protection in the EMPA-REG OUTCOME Trial: a “Thrifty Substrate” hypothesis. Diabetes Care. 2016;39(7):1108–14.PubMedCrossRef Ferrannini E, Mark M, Mayoux E. CV protection in the EMPA-REG OUTCOME Trial: a “Thrifty Substrate” hypothesis. Diabetes Care. 2016;39(7):1108–14.PubMedCrossRef
69.
go back to reference Garvey WT, Van Gaal L, Leiter LA, Vijapurkar U, List J, Cuddihy R, et al. Effects of canagliflozin versus glimepiride on adipokines and inflammatory biomarkers in type 2 diabetes. Metab Clin Exp. 2018;85:32–7.PubMedCrossRef Garvey WT, Van Gaal L, Leiter LA, Vijapurkar U, List J, Cuddihy R, et al. Effects of canagliflozin versus glimepiride on adipokines and inflammatory biomarkers in type 2 diabetes. Metab Clin Exp. 2018;85:32–7.PubMedCrossRef
70.
go back to reference Byrne NJ, Matsumura N, Maayah ZH, Ferdaoussi M, Takahara S, Darwesh AM, et al. Empagliflozin Blunts worsening cardiac dysfunction associated with reduced NLRP3 (Nucleotide-Binding Domain-Like Receptor Protein 3) inflammasome activation in heart failure. Circ Heart Fail. 2020;13(1):e006277.PubMedCrossRef Byrne NJ, Matsumura N, Maayah ZH, Ferdaoussi M, Takahara S, Darwesh AM, et al. Empagliflozin Blunts worsening cardiac dysfunction associated with reduced NLRP3 (Nucleotide-Binding Domain-Like Receptor Protein 3) inflammasome activation in heart failure. Circ Heart Fail. 2020;13(1):e006277.PubMedCrossRef
72.
go back to reference Kumar K, Kheiri B, Simpson TF, Osman M, Rahmouni H. Sodium-glucose cotransporter 2 inhibitors in heart failure: a meta-analysis of randomized clinical trials. Am J Med. 2020;133:e625–30.PubMedCrossRef Kumar K, Kheiri B, Simpson TF, Osman M, Rahmouni H. Sodium-glucose cotransporter 2 inhibitors in heart failure: a meta-analysis of randomized clinical trials. Am J Med. 2020;133:e625–30.PubMedCrossRef
73.
go back to reference Matsumura K, Sugiura T. Effect of sodium glucose cotransporter 2 inhibitors on cardiac function and cardiovascular outcome: a systematic review. Cardiovasc Ultrasound. 2019;17(1):26.PubMedPubMedCentralCrossRef Matsumura K, Sugiura T. Effect of sodium glucose cotransporter 2 inhibitors on cardiac function and cardiovascular outcome: a systematic review. Cardiovasc Ultrasound. 2019;17(1):26.PubMedPubMedCentralCrossRef
74.
go back to reference Lan NSR, Fegan PG, Yeap BB, Dwivedi G. The effects of sodium-glucose cotransporter 2 inhibitors on left ventricular function: current evidence and future directions. ESC Heart Fail. 2019;6(5):927–35.PubMedPubMedCentralCrossRef Lan NSR, Fegan PG, Yeap BB, Dwivedi G. The effects of sodium-glucose cotransporter 2 inhibitors on left ventricular function: current evidence and future directions. ESC Heart Fail. 2019;6(5):927–35.PubMedPubMedCentralCrossRef
75.
go back to reference Tanaka H, Hirata KI. Potential impact of SGLT2 inhibitors on left ventricular diastolic function in patients with diabetes mellitus. Heart Fail Rev. 2018;23(3):439–44.PubMedCrossRef Tanaka H, Hirata KI. Potential impact of SGLT2 inhibitors on left ventricular diastolic function in patients with diabetes mellitus. Heart Fail Rev. 2018;23(3):439–44.PubMedCrossRef
76.
go back to reference Santos-Gallego CG, Garcia-Ropero A, Mancini D, Pinney SP, Contreras JP, Fergus I, et al. Rationale and design of the EMPA-TROPISM Trial (ATRU-4): are the “Cardiac Benefits” of empagliflozin independent of its hypoglycemic activity? Cardiovasc Drugs Ther. 2019;33(1):87–95.PubMedCrossRef Santos-Gallego CG, Garcia-Ropero A, Mancini D, Pinney SP, Contreras JP, Fergus I, et al. Rationale and design of the EMPA-TROPISM Trial (ATRU-4): are the “Cardiac Benefits” of empagliflozin independent of its hypoglycemic activity? Cardiovasc Drugs Ther. 2019;33(1):87–95.PubMedCrossRef
77.
go back to reference Natali A, Nesti L, Fabiani I, Calogero E, Di Bello V. Impact of empagliflozin on subclinical left ventricular dysfunctions and on the mechanisms involved in myocardial disease progression in type 2 diabetes: rationale and design of the EMPA-HEART trial. Cardiovasc Diabetol. 2017;16(1):130.PubMedPubMedCentralCrossRef Natali A, Nesti L, Fabiani I, Calogero E, Di Bello V. Impact of empagliflozin on subclinical left ventricular dysfunctions and on the mechanisms involved in myocardial disease progression in type 2 diabetes: rationale and design of the EMPA-HEART trial. Cardiovasc Diabetol. 2017;16(1):130.PubMedPubMedCentralCrossRef
78.
go back to reference Abraham WT, Ponikowski P, Brueckmann M, Zeller C, Macesic H, Peil B, et al. Rationale and design of the EMPERIAL-Preserved and EMPERIAL-Reduced trials of empagliflozin in patients with chronic heart failure. Eur J Heart Fail. 2019;21(7):932–42.PubMedCrossRef Abraham WT, Ponikowski P, Brueckmann M, Zeller C, Macesic H, Peil B, et al. Rationale and design of the EMPERIAL-Preserved and EMPERIAL-Reduced trials of empagliflozin in patients with chronic heart failure. Eur J Heart Fail. 2019;21(7):932–42.PubMedCrossRef
Metadata
Title
Effect of sodium–glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis
Authors
Yi-Wen Yu
Xue-Mei Zhao
Yun-Hong Wang
Qiong Zhou
Yan Huang
Mei Zhai
Jian Zhang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2021
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-020-01209-y

Other articles of this Issue 1/2021

Cardiovascular Diabetology 1/2021 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

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

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

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

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

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

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