Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Internal Medicine Neurology Oncology Pediatrics Respiratory Medicine Surgery
Congress Coverage
2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting

Keynote Webinar | Spotlight on Diet and Diabetes

Watch on-demand

An expert-led symposium exploring the prevention and management of type 2 diabetes through dietary interventions. 
ADVANCED SEARCH
Log in
Top
Journal of Diabetes & Metabolic Disorders
Published in: Journal of Diabetes & Metabolic Disorders 2/2023

22-09-2023 | Empagliflozin | Research article

Empagliflozin improves high-sensitive cardiac troponin-I and high-density lipoprotein cholesterol in patients with type 2 diabetes mellitus and coronary artery disease: a post-hoc analysis of EMPA-CARD Trial

Authors: Homa Taheri, Hossein Chiti, Tara Reshadmanesh, Sepehr Gohari, Ahmad Jalilvand, Shahram Arsang-Jang, Faramarz Ismail-Beigi, Samin Ghanbari, Mohsen Dadashi, Atieh Asgari, Mahsa Mahjani, Amir Karbalaee‑Hasani, Hassan Ahangar

Published in: Journal of Diabetes & Metabolic Disorders | Issue 2/2023

Login to get access

Abstract

Background

Empagliflozin is a sodium glucose cotransporter-2 (SGLT2) inhibitor that has been suggested to improve cardiac function and vascular recovery. The risk of coronary artery diseases is much higher in diabetic patients and is associated with greater morbidity and mortality. High-sensitivity cardiac troponin-I (hs-cTnI) is an important prognostic biomarker in cardiac diseases. Therefore, this study aimed to investigate the effect of empagliflozin compared to placebo on changes in hs-cTnI and lipid profile after 26 weeks of treatment.

Methods

This was an ancillary study in a randomized trial of patients with concomitant type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) (The EMPA-CARD study). Patients who were already on standard anti-diabetic/anti-ischemic medications were randomized to receive either placebo or empagliflozin 10 mg/daily. Serum hs-cTnI and lipid profile were measured at baseline and after 26 weeks.

Results

Of the 95 randomized patients, hs-cTnI and lipid profile were measured for a total of 77 patients. No significant difference was observed regarding the baseline characteristics between the two arms. Compared to placebo, empagliflozin significantly reduced hs-cTnI after 26 weeks (mean difference (MD) of -13.242, 95%CI: -14.151 to -12.333, p < 0.001). In the empagliflozin group, non-significant reductions in total cholesterol, LDL-C, and triglyceride have resulted; however, there was an increase in HDL-C level (MD = 2.40,95%CI:0.16–4.60, p < 0.04).

Conclusion

Empagliflozin compared to placebo was superior in reducing circulating hs-cTnI that may indicate improvements in cardiomyocytes function in patients with T2DM and CAD. Moreover, empagliflozin had a modest impact on the serum lipid profile biomarkers.

Trial registration

The original EMPA-CARD study has been registered in Iranian Registry of Clinical Trials. www.​IRCT.​ir, Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.
Literature
1.
Lazar DR, Lazar F-L, Homorodean C, Cainap C, Focsan M, Cainap S, et al. High-sensitivity troponin: a review on characteristics, assessment, and clinical implications. Dis Markers. 2022;2022.
2.
Hillis GS, Welsh P, Chalmers J, Perkovic V, Chow CK, Li Q, et al. The relative and combined ability of high-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide to predict cardiovascular events and death in patients with type 2 diabetes. Diabetes Care. 2014;37(1):295–303. CrossRefPubMed
3.
Chilton R, Tikkanen I, Cannon C, Crowe S, Woerle H, Broedl U, et al. Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes Obes Metab. 2015;17(12):1180–93. CrossRefPubMedPubMedCentral
4.
Sinha B, Ghosal S. Meta-analyses of the effects of DPP-4 inhibitors, SGLT2 inhibitors and GLP1 receptor analogues on cardiovascular death, myocardial infarction, stroke and hospitalization for heart failure. Diabetes Res Clin Pract. 2019;150:8–16. CrossRefPubMed
5.
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. CrossRefPubMed
6.
Calapkulu M, Cander S, Gul OO, Ersoy C. Lipid profile in type 2 diabetic patients with new dapagliflozin treatment; actual clinical experience data of six months retrospective lipid profile from single center. Diabetes Metab Syndr. 2019;13(2):1031–4. CrossRefPubMed
7.
Sanchez-Garcia A, Simental-Mendia M, Millan-Alanis JM, Simental-Mendia LE. Effect of sodium-glucose co-transporter 2 inhibitors on lipid profile: a systematic review and meta-analysis of 48 randomized controlled trials. Pharmacol Res. 2020;160: 105068. CrossRefPubMed
8.
9.
Gohari S, Reshadmanesh T, Khodabandehloo H, Fathi M, Ahangar H, Arsang-Jang S, et al. Study rationale and design of a study of EMPAgliflozin’s effects in patients with type 2 diabetes mellitus and Coronary ARtery disease: the EMPA-CARD randomized controlled trial. BMC Cardiovasc Disord. 2021;21(1):1–11. CrossRef
10.
Vickers AJ. Parametric versus non-parametric statistics in the analysis of randomized trials with non-normally distributed data. BMC Med Res Methodol. 2005;5(1):1–12. CrossRef
11.
Tsutamoto T, Kawahara C, Nishiyama K, Yamaji M, Fujii M, Yamamoto T, et al. Prognostic role of highly sensitive cardiac troponin I in patients with systolic heart failure. Am Heart J. 2010;159(1):63–7. CrossRefPubMed
12.
Bohula May EA, Bonaca MP, Jarolim P, Antman EM, Braunwald E, Giugliano RP, et al. Prognostic performance of a high-sensitivity cardiac troponin I assay in patients with non–ST-elevation acute coronary syndrome. Clin Chem. 2014;60(1):158–64. CrossRefPubMed
13.
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. CrossRefPubMed
14.
Paolisso P, Bergamaschi L, Santulli G, Gallinoro E, Cesaro A, Gragnano F, et al. Infarct size, inflammatory burden, and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry. Cardiovasc Diabetol. 2022;21(1):77. CrossRefPubMedPubMedCentral
15.
Packer M, Januzzi JL, Ferreira JP, Anker SD, Butler J, Filippatos G, et al. Concentration-dependent clinical and prognostic importance of high-sensitivity cardiac troponin T in heart failure and a reduced ejection fraction and the influence of empagliflozin: the EMPEROR-Reduced trial. Eur J Heart Fail. 2021;23(9):1529–38. CrossRefPubMed
16.
17.
Lee MM, Brooksbank KJ, Wetherall K, Mangion K, Roditi G, Campbell RT, et al. Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF). Circulation. 2021;143(6):516–25. CrossRefPubMed
18.
Januzzi JL Jr, Butler J, Zannad F, Filippatos G, Ferreira JP, Pocock SJ, et al. Prognostic implications of N-Terminal Pro-B-Type natriuretic peptide and high-sensitivity cardiac troponin T in EMPEROR-preserved. JACC Heart Fail. 2022;10(7):512–24. CrossRefPubMed
19.
Zelniker TA, Morrow DA, Mosenzon O, Goodrich EL, Jarolim P, Murphy SA, et al. Relationship between baseline cardiac biomarkers and cardiovascular death or hospitalization for heart failure with and without sodium-glucose co-transporter 2 inhibitor therapy in DECLARE-TIMI 58. Eur J Heart Fail. 2021;23(6):1026–36. CrossRefPubMed
20.
Verma S, McMurray JJ. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018;61(10):2108–17. CrossRefPubMed
21.
Kocak EF, Kocak C, Aksoy A, Isiklar OO, Akcilar R, Ozdomanic IF, et al. High-sensitivity cardiac troponin T is more helpful in detecting peri-operative myocardial injury and apoptosis during coronary artery bypass graft surgery: cardiovascular topics. Cardiovasc J Afr. 2015;26(6):234–41. CrossRefPubMedPubMedCentral
22.
Fadini GP, Bonora BM, Zatti G, Vitturi N, Iori E, Marescotti MC, et al. Effects of the SGLT2 inhibitor dapagliflozin on HDL cholesterol, particle size, and cholesterol efflux capacity in patients with type 2 diabetes: a randomized placebo-controlled trial. Cardiovasc Diabetol. 2017;16(1):1–10. CrossRef
23.
Pujante P, Ares J, Maciá C, Escobedo RR, Menéndez E, Delgado E. Efficacy of sodium glucose cotransporter 2 inhibitors as an adjunct treatment for patients with diabetes type 2. Med Clín (English Edition). 2019;152(11):438–41. CrossRef
24.
Ozcelik S, Celik M, Vural A, Aydin B. The effect of low and high dose empagliflozin on HbA1c and lipid profile in type 2 diabetes mellitus: a real-world data. North Clin İstanbul. 2020;7(2):167.
25.
Castellana M, Cignarelli A, Brescia F, Perrini S, Natalicchio A, Laviola L, et al. Efficacy and safety of GLP-1 receptor agonists as add-on to SGLT2 inhibitors in type 2 diabetes mellitus: a meta-analysis. Sci Rep. 2019;9(1):1–8. CrossRef
26.
Kohler S, Zeller C, Iliev H, Kaspers S. Safety and tolerability of empagliflozin in patients with type 2 diabetes: pooled analysis of phase I-III clinical trials. Adv Ther. 2017;34(7):1707–26. CrossRefPubMedPubMedCentral
27.
Lund SS, Sattar N, Salsali A, Neubacher D, Ginsberg HN. Potential contribution of haemoconcentration to changes in lipid variables with empagliflozin in patients with type 2 diabetes: a post hoc analysis of pooled data from four phase 3 randomized clinical trials. Diabetes Obes Metab. 2021;23(12):2763–74. CrossRefPubMedPubMedCentral
28.
Rau M, Thiele K, Hartmann N-UK, Möllmann J, Wied S, Böhm M, et al. Effects of empagliflozin on lipoprotein subfractions in patients with type 2 diabetes: data from a randomized, placebo-controlled study. Atherosclerosis. 2021;330:8–13.
29.
Briand F, Mayoux E, Brousseau E, Burr N, Urbain I, Costard C, et al. Empagliflozin, via switching metabolism toward lipid utilization, moderately increases LDL cholesterol levels through reduced LDL catabolism. Diabetes. 2016;65(7):2032–8. CrossRefPubMed
30.
31.
Kovacs C, Seshiah V, Swallow R, Jones R, Rattunde H, Woerle H, et al. Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab. 2014;16(2):147–58. CrossRefPubMed
32.
Matthaei S, Bowering K, Rohwedder K, Grohl A, Parikh S, Group S. Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Diabetes Care. 2015;38(3):365-72.
33.
Osataphan S, Macchi C, Singhal G, Chimene-Weiss J, Sales V, Kozuka C, et al. SGLT2 inhibition reprograms systemic metabolism via FGF21-dependent and-independent mechanisms. JCI insight. 2019;4(5).
34.
Adingupu DD, Göpel SO, Grönros J, Behrendt M, Sotak M, Miliotis T, et al. SGLT2 inhibition with empagliflozin improves coronary microvascular function and cardiac contractility in prediabetic ob/ob−/− mice. Cardiovasc Diabetol. 2019;18(1):1–15. CrossRef
35.
Li D, Wu T, Wang T, Wei H, Wang A, Tang H, et al. Effects of sodium glucose cotransporter 2 inhibitors on risk of dyslipidemia among patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Pharmacoepidemiol Drug Saf. 2020;29(5):582–90. CrossRefPubMed
36.
Basu D, Huggins L-A, Scerbo D, Obunike J, Mullick AE, Rothenberg PL, et al. Mechanism of increased LDL (low-density lipoprotein) and decreased triglycerides with SGLT2 (sodium-glucose cotransporter 2) inhibition. Arterioscler Thromb Vasc Biol. 2018;38(9):2207–16. CrossRefPubMedPubMedCentral
37.
Lee MH, Neeland IJ, de Albuquerque RN, Hughes C, Malloy CR, Jin ES. A randomized clinical trial evaluating the effect of empagliflozin on triglycerides in obese adults: role of visceral fat. Metabolism open. 2022;13: 100161. CrossRefPubMed
Metadata
Title
Empagliflozin improves high-sensitive cardiac troponin-I and high-density lipoprotein cholesterol in patients with type 2 diabetes mellitus and coronary artery disease: a post-hoc analysis of EMPA-CARD Trial
Authors
Homa Taheri
Hossein Chiti
Tara Reshadmanesh
Sepehr Gohari
Ahmad Jalilvand
Shahram Arsang-Jang
Faramarz Ismail-Beigi
Samin Ghanbari
Mohsen Dadashi
Atieh Asgari
Mahsa Mahjani
Amir Karbalaee‑Hasani
Hassan Ahangar
Publication date
22-09-2023
Publisher
Springer International Publishing
Published in
Journal of Diabetes & Metabolic Disorders / Issue 2/2023
Electronic ISSN: 2251-6581
DOI
https://doi.org/10.1007/s40200-023-01305-2

Other articles of this Issue 2/2023

Journal of Diabetes & Metabolic Disorders 2/2023 Go to the issue

Correction

Correction to: Metformin inhibits cardiometabolic syndrome associated cognitive deficits in high fat diet rats

Review article

Engineered probiotics introduced to improve intestinal microecology for the treatment of chronic diseases: present state and perspectives

Research article

The diabetic patient between sustainability and effectiveness of new treatments

Research Article

MiR-29b modulates DNA methylation in promoter region of miR-130b in mouse model of Diabetic nephropathy

Research article

Effect of metformin on Wnt5a in individuals new-onset type 2 diabetes with different body mass indexes: The evidences from the real word research

Study Protocol

Pituitary tumor registry: a multidisciplinary program protocol
Webinar | 08-11-2023 | 18:00 (CET)

Keynote Webinar | Spotlight on Diet and Diabetes

Watch now

An expert-led symposium exploring the prevention and management of type 2 diabetes through dietary interventions. Highlights include discussion of the recent EASD guidelines, therapeutic diets, food types and processing, plus psychological factors that influence patient success, and the drivers of healthy eating and diabetes control.
Prof. Mike Lean
Prof. Falko Sniehotta
Image Credits