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

Overview

Journal J Diabetes Metab Disord

Specialty Endocrinology

Date 2023 Nov 17

PMID 37975102

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

Affiliations

Soon will be listed here.

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, < 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, < 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.

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References

Matthaei S, Bowering K, Rohwedder K, Grohl A, Parikh 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. DOI: 10.2337/dc14-0666. View

Zelniker T, Morrow D, Mosenzon O, Goodrich E, Jarolim P, Murphy S . 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. 2020; 23(6):1026-1036. DOI: 10.1002/ejhf.2073. View

Castellana M, Cignarelli A, Brescia F, Perrini S, Natalicchio A, Laviola L . 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):19351. PMC: 6920368. DOI: 10.1038/s41598-019-55524-w. View

Januzzi Jr J, Butler J, Jarolim P, Sattar N, Vijapurkar U, Desai M . Effects of Canagliflozin on Cardiovascular Biomarkers in Older Adults With Type 2 Diabetes. J Am Coll Cardiol. 2017; 70(6):704-712. DOI: 10.1016/j.jacc.2017.06.016. View

Kocak E, Kocak C, Aksoy A, Isiklar O, Akcilar R, Ozdomanic I . High-sensitivity cardiac troponin T is more helpful in detecting peri-operative myocardial injury and apoptosis during coronary artery bypass graft surgery. Cardiovasc J Afr. 2015; 26(6):234-41. PMC: 4780022. DOI: 10.5830/CVJA-2015-052. View

Tsutamoto T, Kawahara C, Nishiyama K, Yamaji M, Fujii M, Yamamoto T . Prognostic role of highly sensitive cardiac troponin I in patients with systolic heart failure. Am Heart J. 2010; 159(1):63-7. DOI: 10.1016/j.ahj.2009.10.022. View

Lee M, Brooksbank K, Wetherall K, Mangion K, Roditi G, Campbell R . 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. 2020; 143(6):516-525. PMC: 7864599. DOI: 10.1161/CIRCULATIONAHA.120.052186. View

Fadini G, Bonora B, Zatti G, Vitturi N, Iori E, Marescotti M . 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):42. PMC: 5379610. DOI: 10.1186/s12933-017-0529-3. View

Basu D, Huggins L, Scerbo D, Obunike J, Mullick A, Rothenberg P . Mechanism of Increased LDL (Low-Density Lipoprotein) and Decreased Triglycerides With SGLT2 (Sodium-Glucose Cotransporter 2) Inhibition. Arterioscler Thromb Vasc Biol. 2018; 38(9):2207-2216. PMC: 6207215. DOI: 10.1161/ATVBAHA.118.311339. View

10.

Rau M, Thiele K, Hartmann N, Mollmann J, Wied S, Bohm M . Effects of empagliflozin on lipoprotein subfractions in patients with type 2 diabetes: data from a randomized, placebo-controlled study. Atherosclerosis. 2021; 330:8-13. DOI: 10.1016/j.atherosclerosis.2021.06.915. View

11.

Sanchez-Garcia A, Simental-Mendia M, Millan-Alanis J, Simental-Mendia L . 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. DOI: 10.1016/j.phrs.2020.105068. View

12.

Vickers A . Parametric versus non-parametric statistics in the analysis of randomized trials with non-normally distributed data. BMC Med Res Methodol. 2005; 5:35. PMC: 1310536. DOI: 10.1186/1471-2288-5-35. View

13.

Chilton R, Tikkanen I, Cannon C, Crowe S, Woerle H, Broedl U . 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. PMC: 5057299. DOI: 10.1111/dom.12572. View

14.

Hillis G, Welsh P, Chalmers J, Perkovic V, Chow C, Li Q . 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. 2013; 37(1):295-303. DOI: 10.2337/dc13-1165. View

15.

Calapkulu M, Cander S, Gul O, 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):1031-1034. DOI: 10.1016/j.dsx.2019.01.016. View

16.

Januzzi Jr J, Butler J, Zannad F, Filippatos G, Ferreira J, Pocock S . 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):512-524. DOI: 10.1016/j.jchf.2022.05.004. View

17.

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 Istanb. 2020; 7(2):167-173. PMC: 7117635. DOI: 10.14744/nci.2019.22697. View

18.

Lee M, Neeland I, de Albuquerque Rocha N, Hughes C, Malloy C, Jin E . A randomized clinical trial evaluating the effect of empagliflozin on triglycerides in obese adults: Role of visceral fat. Metabol Open. 2022; 13:100161. PMC: 8728102. DOI: 10.1016/j.metop.2021.100161. View

19.

Lazar D, Lazar F, Homorodean C, Cainap C, Focsan M, Cainap S . High-Sensitivity Troponin: A Review on Characteristics, Assessment, and Clinical Implications. Dis Markers. 2022; 2022:9713326. PMC: 8965602. DOI: 10.1155/2022/9713326. View

20.

Li D, Wu T, Wang T, Wei H, Wang A, Tang H . 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):582-590. DOI: 10.1002/pds.4985. View