Sodium-glucose cotransporter 2 inhibitors in patients with acute coronary syndrome: a systematic review and meta-analysis

Aim. To analyze published clinical trials, to assess the effectiveness of early initiation of sodium-glucose cotransporter 2 (SGLT-2) inhibitors in preventing cardiovascular events and all-cause mortality in patients with acute coronary syndrome.

Material and methods. The meta-analysis was performed in accordance with PRISMA guidelines based on a literature search of the PubMed/MEDLINE database for the period from 2021 to July 7, 2025. Keywords included the MeSH terms “sodium–glucose co-transporter 2 inhibitors” OR “SGLT2” OR “empagliflozin” OR “dapagliflozin” OR “canagliflozin” OR “sotagliflozin” AND “myocardial infarction” OR “acute coronary syndrome”. The ROBIS-I and RoB2 tools were used to assess the risk of bias in the included studies.

Results. The initial search strategy identified 13,879 publications. After excluding records that did not meet the inclusion criteria, 15 studies with no exclusion criteria were included in the analysis. The meta-analysis included 118,332 patients from 15 studies (54,853 patients received SGLT-2 inhibitors, 63479 were included in the control group). The results showed that patients with acute coronary syndrome treated with SGLT-2 inhibitors had a 39% lower rate of all-cause mortality (OR=0.61, 95% CI=0.46-0.81, p=0.006) and a 32% lower rate of hospitalisation for heart failure (HR=0.68, 95% CI=0.54-0.86, p=0.001) compared with patients who did not receive this group of drugs. When divided into groups that included only patients with type 2 diabetes mellitus and patients with and without type 2 diabetes mellitus, a decrease in all-cause mortality and the number of hospitalizations due to heart failure was achieved only in the group of patients with type 2 diabetes mellitus (OR=0.43, 95% CI=0.31-0.59, p<0.001 and HR=0.63, 95% CI=0.48-0.82, p<0.001, respectively). While in studies in which type 2 diabetes was not a mandatory inclusion criterion or was an exclusion criterion, SGLT-2 inhibitors were not associated with a decrease in both deaths from all causes (OR=0.77, 95% CI=0.55-1.09, p=0.14) and the number of hospitalisations due to the cause of heart failure (HR=0.77, 95% CI=0.52-1.14, p=0.19). Patients who received SGLT-2 inhibitors for one reason or another before the onset of acute coronary syndrome had a more pronounced reduction in both the risk of death from all causes (OR=0.36, 95% CI=0.29-0.45, p<0.001) and hospitalisation due to heart failure (HR=0.47, 95% CI=0.24-0.89, p=0.02) than patients who started SGLT-2 inhibitors during hospitalisation due to acute coronary syndrome (OR=0.73, 95% CI=0.55–0.97, p=0.03 and HR=0.67, 95% CI=0.53-0.86, p=0.001, respectively). SGLT-2 inhibitors did not reduce the risk of death from cardiovascular causes (HR=0.98, 95% CI=0.80-1.21, p=0.86), nonfatal stroke (HR=0.98, 95% CI=0.93-1.03, p=0.44).

Conclusion. Our meta-analysis shows that in patients with acute coronary syndrome, SGLT-2 inhibitors treatment is associated with a reduced risk of death from all causes and hospitalisation due to heart failure, mainly in the group of patients with type 2 diabetes mellitus, but does not affect death from cardiovascular causes.

1. Szummer K, Wallentin L, Lindhagen L, et al. Improved outcomes in patients with ST-elevation myocardial infarction during the last 20 years are related to implementation of evidence-based treatments: experiences from the SWEDEHEART registry 1995-2014. Eur Heart J. 2017;38(41):3056-65. DOI:10.1093/eurheartj/ehx515.

2. McMurray JJV, Solomon SD, Inzucchi SE, et al.; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. DOI:10.1056/NEJMoa1911303.

3. Solomon SD, McMurray JJV, Claggett B, et al.; DELIVER Trial Committees and Investigators. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022;387(12):1089-98. DOI:10.1056/NEJMoa2206286.

4. Liu Y, Wu M, Xu J, et al. Empagliflozin prevents from early cardiac injury post myocardial infarction in non-diabetic mice. Eur J Pharm Sci. 2021;161:105788. DOI:10.1016/j.ejps.2021.105788.

5. Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, 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. DOI:10.1016/j.jacc.2019.01.056.

6. Lim VG, Bell RM, Arjun S, et al. SGLT2 Inhibitor, Canagliflozin, Attenuates Myocardial Infarction in the Diabetic and Nondiabetic Heart. JACC Basic to Transl Sci. 2019;4(1):15-26. DOI:10.1016/j.jacbts.2018.10.002.

7. von Lewinski D, Kolesnik E, Tripolt NJ, et al. Empagliflozin in acute myocardial infarction: the EMMY trial. Eur Heart J. 2022;43(41):4421-32. DOI:10.1093/eurheartj/ehac494.

8. James S, Erlinge D, Storey RF, et al. Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure. NEJM Evid. 2024;3(2):EVIDoa2300286. DOI:10.1056/EVIDoa2300286.

9. Butler J, Jones WS, Udell JA, et al. Empagliflozin after Acute Myocardial Infarction. N Engl J Med. 2024;390(16):1455-66. DOI:10.1056/NEJMoa2314051.

10. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. DOI:10.1136/bmj.n71.

11. Higgins JP, Altman DG, Gotzsche PC, et al.; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. DOI:10.1136/bmj.d5928.

12. Chen J, Chang J, Shi Q, et al. Cardiovascular protective effect of sodium-glucose cotransporter 2 inhibitors on patients with acute coronary syndrome and type 2 diabetes mellitus: a retrospective study. BMC Cardiovasc Disord. 2023;23(1):495. DOI:10.1186/s12872-023-03542-y.

13. Rosén HC, Mohammad MA, Jernberg T, et al. SGLT2 inhibitors for patients with type 2 diabetes mellitus after myocardial infarction: a nationwide observation registry study from SWEDEHEART. Lancet Reg Heal Eur. 2024;45:101032. DOI:10.1016/j.lanepe.2024.101032.

14. Zhu Y, Zhang JL, Yan XJ, et al. Effect of dapagliflozin on the prognosis of patients with acute myocardial infarction undergoing percutaneous coronary intervention. Cardiovasc Diabetol. 2022;21(1):186. DOI:10.1186/s12933-022-01627-0.

15. Paolisso P, Bergamaschi L, Gragnano F, et al. Outcomes in diabetic patients treated with SGLT2-Inhibitors with acute myocardial infarction undergoing PCI: The SGLT2-I AMI PROTECT Registry. Pharmacol Res. 2023;187:106597. DOI:10.1016/j.phrs.2022.106597.

16. Kurozumi A, Shishido K, Yamashita T, et al. Sodium-Glucose Cotransporter-2 Inhibitors Stabilize Coronary Plaques in Acute Coronary Syndrome With Diabetes Mellitus. Am J Cardiol. 2024;214:47-54. DOI:10.1016/j.amjcard.2023.12.056.

17. Marfella R, Sardu C, D’Onofrio N, et al. SGLT-2 inhibitors and in-stent restenosis-related events after acute myocardial infarction: an observational study in patients with type 2 diabetes. BMC Med. 2023;21(1):71. DOI:10.1186/s12916-023-02781-2.

18. Chang TY, Lu CT, Huang HL, et al. Association of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Use With Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus Patients With Stabilized Acute Myocardial Infarction: A Propensity Score Matching Study. Front Cardiovasc Med. 2022;9:882181. DOI:10.3389/fcvm.2022.882181.

19. Cai D, Chen Q, Mao L, et al. Association of SGLT2 inhibitor dapagliflozin with risks of acute kidney injury and all-cause mortality in acute myocardial infarction patients. Eur J Clin Pharmacol. 2024;80(4):613-20. DOI:10.1007/s00228-024-03623-7.

20. Mao L, Cai D, Chi B, et al. Dapagliflozin reduces risk of heart failure rehospitalization in diabetic acute myocardial infarction patients: a propensity scorematched analysis. Eur J Clin Pharmacol. 2023;79(7):915-26. DOI:10.1007/s00228-023-03495-3.

21. Lyu YS, Oh S, Kim JH, et al. Comparison of SGLT2 inhibitors with DPP-4 inhibitors combined with metformin in patients with acute myocardial infarction and diabetes mellitus. Cardiovasc Diabetol. 2023;22(1):185. DOI:10.1186/s12933-023-01914-4.

22. Kwon O, Myong J, Lee Y, et al. Sodium Glucose Cotransporter 2 Inhibitors After Acute Myocardial Infarction in Patients With Type 2 Diabetes: A Population‐ Based Investigation. J Am Heart Assoc. 2023;12(14):e027824. DOI:10.1161/JAHA.122.027824.

23. Ci Mee X, Kheng Lim G, Ibrahim R, et al. SGLT2 inhibitors and cardiovascular outcomes in patients with acute myocardial infarction: a retrospective cohort analysis. Eur Hear J Cardiovasc Pharmacother. 2025;11(4):334-42. DOI:10.1093/ehjcvp/pvaf026.

24. Adel SMH, Jorfi F, Mombeini H, et al. Effect of a low dose of empagliflozin on short-term outcomes in type 2 diabetics with acute coronary syndrome after percutaneous coronary intervention. Saudi Med J. 2022;43(5):458-64. DOI:10.15537/smj.2022.43.5.20220018.

25. Lee SY, Lee TW, Park GT, et al. Sodium/glucose Co-Transporter 2 Inhibitor, Empagliflozin, Alleviated Transient Expression of SGLT2 after Myocardial Infarction. Korean Circ J. 2021;51(3):251-62. DOI:10.4070/kcj.2020.0303.

26. Jiang K, Xu Y, Wang D, et al. Cardioprotective mechanism of SGLT2 inhibitor against myocardial infarction is through reduction of autosis. Protein Cell. 2022;13(5):336-59. DOI:10.1007/s13238-020-00809-4.

27. Lee TM, Chang NC, Lin SZ. Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic Biol Med. 2017;104:298-310. DOI:10.1016/j.freeradbiomed.2017.01.035.

28. Cowie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol. 2020;17(12):761-72. DOI:10.1038/s41569-020-0406-8.

29. Sinha T, Khilji F, Laraib F, et al. The Effectiveness of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors on Cardiovascular Outcomes and All-Cause Mortality in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis. Cureus. 2024;16(4):e58019. DOI:10.7759/cureus.58019.

30. Suciu IM, Luca SA, Crișan S, et al. Do SGLT2 Inhibitors Improve Cardiovascular Outcomes After Acute Coronary Syndrome Regardless of Diabetes? A Systematic Review and Meta-Analysis. Medicina (Kaunas). 2025;61(10):1866. DOI:10.3390/medicina61101866.