Prospective Evaluation of Atrial Fibrillation Risk in Type 2 Diabetes Comparing SGLT-2 Inhibitors and DPP-4 Inhibitors
DOI:
https://doi.org/10.70749/ijbr.v3i3.797Keywords:
Atrial Fibrillation, Type 2 Diabetes, SGLT-2 Inhibitors, DPP-4 InhibitorsAbstract
Background: Type 2 diabetes mellitus (T2DM) is a major risk factor of atrial fibrillation (AF). In particular, sodium glucose co-transporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors are often used to treat T2DM, and effects of these drugs on risk for AF are unknown. The goal of this study was to investigate if SGLT 2 inhibitor are associated with an increase in the incidence of new onset AF, as well as the incidence of cardiovascular outcomes, versus DPP4 inhibitors. Prospective cohort study was conducted at Lady Reading Hospital, Peshawar from July 2024 to December 2024 in 370 T2DM patients aged 40 to 75 years, started on SGLT2 inhibitors (n= 189) or DPP4 inhibitors (n= 181). Follow up was for 6 months and patients were followed up with regular electrocardiographic evaluation for the occurrence of new onset of AF. Other secondary outcomes were hospitalization for ischemic stroke and heart failure. Cox proportional hazards models and Kaplan-Meier survival analysis were used to assess AF risk and cardiovascular outcomes adjusting for confounders, including age, sex, hypertension and BMI. Results: New onset of AF incidence was significantly lower in SGLT-2 inhibitor group (p < 0.05) compared with DPP-4 inhibitor group. As well, SGLT-2 inhibitors also reduced the risk of hospitalization for heart failure or ischemic stroke in patients. The two groups had similar baseline characteristics. TAMP patients treated with SGLT 2 inhibitors had a reduced risk of new onset AF as well as more favorable cardiovascular outcomes compared to TAMP patients treated with DPP 4 inhibitors. These may suggest SGLT-2 inhibitors as a mechanism to suppress both the arrhythmic and cardiovascular manifestations of diabetes. The benefits here warrant further large-scale studies to confirm them.
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Lima, J. E., Moreira, N. C., & Sakamoto-Hojo, E. T. (2022). Mechanisms underlying the pathophysiology of type 2 diabetes: From risk factors to oxidative stress, metabolic dysfunction, and hyperglycemia. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 874, 503437. https://doi.org/10.1016/j.mrgentox.2021.503437
Khin, P. P., Lee, J. H., & Jun, H. S. (2023). Pancreatic beta-cell dysfunction in type 2 diabetes. European Journal of Inflammation, 21, 1721727X231154152. https://doi.org/10.1177/1721727x231154152
Balan, A. I., Halațiu, V. B., & Scridon, A. (2024). Oxidative stress, inflammation, and mitochondrial dysfunction: a link between obesity and atrial fibrillation. Antioxidants, 13(1), 117. https://doi.org/10.3390/antiox13010117
Theofilis, P., Oikonomou, E., Tsioufis, K., & Tousoulis, D. (2023). Diabetes mellitus and heart failure: epidemiology, pathophysiologic mechanisms, and the role of SGLT2 inhibitors. Life, 13(2), 497. https://doi.org/10.3390/life13020497
Aroda, V. R., & Eckel, R. H. (2022). Reconsidering the role of glycaemic control in cardiovascular disease risk in type 2 diabetes: a 21st century assessment. Diabetes, Obesity and Metabolism, 24(12), 2297-2308. https://doi.org/10.1111/dom.14830
Gallardo-Gómez, D., Salazar-Martínez, E., Alfonso-Rosa, R. M., Ramos-Munell, J., del Pozo-Cruz, J., del Pozo Cruz, B., & Álvarez-Barbosa, F. (2024). Optimal dose and type of physical activity to improve glycemic control in people diagnosed with type 2 diabetes: a systematic review and meta-analysis. Diabetes Care, 47(2), 295-303. https://doi.org/10.2337/dc23-0800
Maccari, R., & Ottanà, R. (2022). Sodium-glucose cotransporter inhibitors as antidiabetic drugs: current development and future perspectives. Journal of medicinal chemistry, 65(16), 10848-10881. https://doi.org/10.1021/acs.jmedchem.2c00867
Preda, A., Montecucco, F., Carbone, F., Camici, G. G., Lüscher, T. F., Kraler, S., & Liberale, L. (2024). SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits. Cardiovascular research, 120(5), 443-460. https://doi.org/10.1093/cvr/cvae047
Chen, X., Hocher, C. F., Shen, L., Krämer, B. K., & Hocher, B. (2023). Reno-and cardioprotective molecular mechanisms of SGLT2 inhibitors beyond glycemic control: from bedside to bench. American Journal of Physiology-Cell Physiology, 325(3), C661-C681. https://doi.org/10.1152/ajpcell.00177.2023
O’Hara, D. V., Lam, C. S., McMurray, J. J., Yi, T. W., Hocking, S., Dawson, J., ... & Jardine, M. J. (2024). Applications of SGLT2 inhibitors beyond glycaemic control. Nature Reviews Nephrology, 20(8), 513-529. https://doi.org/10.1038/s41581-024-00836-y
Lopez-Usina, A., Mantilla-Cisneros, C., & Llerena-Velastegui, J. (2024). Comprehensive Benefits of Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure With Reduced Ejection Fraction: A Literature Review. Journal of Clinical Medicine Research, 16(10), 449. https://doi.org/10.14740/jocmr6033
Fan, D., & Wu, R. (2024). Mechanisms of the septic heart: From inflammatory response to myocardial edema. Journal of Molecular and Cellular Cardiology. https://doi.org/10.1016/j.yjmcc.2024.08.003
Florentin, M., Kostapanos, M. S., & Papazafiropoulou, A. K. (2022). Role of dipeptidyl peptidase 4 inhibitors in the new era of antidiabetic treatment. World Journal of Diabetes, 13(2), 85. https://doi.org/10.4239/wjd.v13.i2.85
Javed Naim, M. (2024). A Review of Dipeptidyl Peptidase-4 (DPP-4) and its potential synthetic derivatives in the management of Diabetes Mellitus. Journal of Angiotherapy, 8(1). https://doi.org/10.25163/angiotherapy.819417
Epelde, F. (2024). Impact of DPP-4 Inhibitors in Patients with Diabetes Mellitus and Heart Failure: An In-Depth Review. Medicina, 60(12), 1986. https://doi.org/10.3390/medicina60121986
Patel, S. M., Morrow, D. A., Bellavia, A., Berg, D. D., Bhatt, D. L., Jarolim, P., ... & Bohula, E. A. (2024). Natriuretic peptides, body mass index and heart failure risk: Pooled analyses of SAVOR‐TIMI 53, DECLARE‐TIMI 58 and CAMELLIA‐TIMI 61. European journal of heart failure, 26(2), 260-269. https://doi.org/10.1002/ejhf.3118
Razavi, M., Wei, Y. Y., Rao, X. Q., & Zhong, J. X. (2022). DPP-4 inhibitors and GLP-1RAs: cardiovascular safety and benefits. Military Medical Research, 9(1), 45. https://doi.org/10.1186/s40779-022-00410-2
D’Andrea, E., Wexler, D. J., Kim, S. C., Paik, J. M., Alt, E., & Patorno, E. (2023). Comparing effectiveness and safety of SGLT2 inhibitors vs DPP-4 inhibitors in patients with type 2 diabetes and varying baseline HbA1c levels. JAMA internal medicine, 183(3), 242-254. https://doi.org/10.1001/jamainternmed.2022.6664
Rawshani, A., McGuire, D. K., Omerovic, E., Sattar, N., McMurray, J. J., Smith, U., ... & Rawshani, A. (2023). Cardiac arrhythmias and conduction abnormalities in patients with type 2 diabetes. Scientific reports, 13(1), 1192. https://doi.org/10.1038/s41598-023-27941-5
Al-Falah, M. A. (2024). The Relationship between the Incidence of Atrial Fibrillation and Patients with Type 2 Diabetes Mellitus: A Systematic Review. Saudi J Med Pharm Sci, 10(4), 215-222. https://doi.org/10.36348/sjmps.2024.v10i04.002
GHERASIM, L. (2022). Association of atrial fibrillation with diabetes mellitus, high risk comorbidities. Maedica, 17(1), 143. https://doi.org/10.26574/maedica.2022.17.1.143
Inciardi, R. M., Giugliano, R. P., Park, J. G., Nordio, F., Ruff, C. T., Chen, C., ... & Solomon, S. D. (2023). Risks of heart failure, stroke, and bleeding in atrial fibrillation according to heart failure phenotypes. Clinical Electrophysiology, 9(4), 569-580. https://doi.org/10.1016/j.jacep.2022.11.032
Rafaqat, S., Sharif, S., Murad, M. A., Bibi, F., & Rafaqat, S. (2024). The Role of Different Components of Metabolic Syndrome in the Pathogenesis of Atrial Fibrillation. JOURNAL OF CARDIAC ARRHYTHMIAS, 37. https://doi.org/10.24207/jca.v37i1.3501
Wang, M., Zhang, Y., Wang, Z., Liu, D., Mao, S., & Liang, B. (2022). The effectiveness of SGLT2 inhibitor in the incidence of atrial fibrillation/atrial flutter in patients with type 2 diabetes mellitus/heart failure: a systematic review and meta-analysis. Journal of thoracic disease, 14(5), 1620. https://doi.org/10.21037/jtd-22-550
Lv, Q., Yang, Y., Lv, Y., Wu, Q., Hou, X., Li, L., ... & Wang, S. (2024). Effect of different hypoglycemic drugs and insulin on the risk of new-onset atrial fibrillation in people with diabetes: a network meta-analysis. European Journal of Medical Research, 29(1), 399. https://doi.org/10.1186/s40001-024-01954-w
Stachteas, P., Nasoufidou, A., Karagiannidis, E., Patoulias, D., Karakasis, P., Alexiou, S., ... & Fragakis, N. (2024). The Role of Sodium Glucose Co-Transporter 2 Inhibitors in Atrial Fibrillation: A Comprehensive Review. Journal of Clinical Medicine, 13(18), 5408. https://doi.org/10.3390/jcm13185408
Oyama, K., Raz, I., Cahn, A., Kuder, J., Murphy, S. A., Bhatt, D. L., ... & Wiviott, S. D. (2022). Obesity and effects of dapagliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus in the DECLARE–TIMI 58 trial. European heart journal, 43(31), 2958-2967. https://doi.org/10.1093/eurheartj/ehab530
Schechter, M., Wiviott, S. D., Raz, I., Goodrich, E. L., Rozenberg, A., Yanuv, I., ... & Mosenzon, O. (2023). Effects of dapagliflozin on hospitalisations in people with type 2 diabetes: post-hoc analyses of the DECLARE-TIMI 58 trial. The lancet Diabetes & endocrinology, 11(4), 233-241. https://doi.org/10.1016/s2213-8587(23)00009-8
Mauriello, A., Ascrizzi, A., Roma, A. S., Molinari, R., Caturano, A., Imbalzano, E., ... & Russo, V. (2024). Effects of Heart Failure Therapies on Atrial Fibrillation: Biological and Clinical Perspectives. Antioxidants, 13(7), 806. https://doi.org/10.3390/antiox13070806
Kutz, A., Kim, D. H., Wexler, D. J., Liu, J., Schneeweiss, S., Glynn, R. J., & Patorno, E. (2023). Comparative cardiovascular effectiveness and safety of SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors according to frailty in type 2 diabetes. Diabetes Care, 46(11), 2004-2014. https://doi.org/10.2337/dc23-0671
Fichadiya, A., Quinn, A., Au, F., Campbell, D., Lau, D., Ronksley, P., ... & Chew, D. S. (2024). Association between sodium–glucose cotransporter-2 inhibitors and arrhythmic outcomes in patients with diabetes and pre-existing atrial fibrillation. Europace, 26(3), euae054. https://doi.org/10.1093/europace/euae054
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