The influence of SGLT-2 inhibitors on lipid profiles in heart failure patients: a systematic review and meta-analysis.

Am J Cardiovasc Dis 2024;14(6):295-305 www.AJCD.us /ISSN:2160-200X/AJCD0156634 Review Article The influence of SGLT-2 inhibitors on lipid profiles in heart failure patients: a systematic review and meta-analysis Seyed Mohammad Mahdi Meybodi1,2*, Mohammad Amin Karimi3*, Kourosh Mousazadeh4*, Kamyar Khorsand5*, Samira Masoumi6, Seyed Abbas Pakmehr7, Mahsa Asadi Anar10, Nahid Samadi8, Mohadeseh Poudineh9, Mohammad Rahmanian10, Shirin Yaghoobpoor10, Arash Rahimi10, Fariba Arbab Mojeni11, Seyedeh Zahra Banihashemian12, Mina Masoodi13, Komeil Aghazadeh-Habashi14, Atousa Ghorbani15, Arezoo Faridzadeh16,17, Niloofar Deravi10 Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran; 2Young Researchers and Elite Club, Islamic Azad University, Tabriz Branch, Tabriz, Iran; 3School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Islamic Azad University, Tehran Medical Branch, Tehran, Iran; 5Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 6Islamic Azad University, Pharmaceutical Sciences Branch (IAUPS), Tehran, Iran; 7School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; 8Student Research Committee, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; 9Student Research Committee, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran; 10Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 11Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; 12Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran; 13 Faculty of Medicine, Islamic Azad University, Shahrood Branch, Shahrood, Iran; 14Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; 15Department of Biology, Faculty of Basic Sciences, Islamic Azad University, East Tehran Branch (Ghiamdasht), Tehran, Iran; 16Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 17Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. *Equal contributors. 1 Received March 18, 2024; Accepted August 29, 2024; Epub December 15, 2024; Published December 30, 2024 Abstract: Background and aim: Sodium-glucose cotransporter two inhibitors can reduce cardiovascular events by modulating lipid profiles in patients with heart failure, irrespective of diabetes status. In this study, we aimed to assess the effects of SGLT-2 inhibitors on the lipid profiles of patients with heart failure via a meta-analysis. Methods: The PubMed, Scopus, Web of Science, and Google Scholar databases were searched up to 2023 to retrieve relevant article titles, abstracts, and full texts. STATA software was used to conduct the meta-analysis. Result: The Forest plot of fasting blood sugar levels in patients receiving SGLT-2 inhibitors differed significantly from those the in control group (mean difference = -0.08, 95% CI [-0.13, -0.02], P < 0.05). Analysis of lipid profile parameters, including total cholesterol, triglyceride, HDL, and LDL in patients with HF receiving SGLT-2 inhibitors, did not show a notable difference from the control group (P > 0.005). However, the mean difference was towards the reduction of LDL, cholesterol, and triglycerides and showed an increase in HDL levels. Egger’s test for publication bias revealed some publication bias (P < 0.05). Conclusion: Our topic analysis did not reveal any notable alterations in the lipid profile. To arrive at a more definite agreement, further research on subjects with heart failure is necessary because there is currently insufficient evidence. Keywords: SGLT-2 inhibitors, heart failure, lipid, HDL, LDL, cholesterol, triglyceride lipid profiles, dapagliflozin, empagliflozin, canagliflozin Introduction Among the different types of sodium-glucose transporter proteins in humans, we can men- tion SGLT1 (mainly in the intestine) and SGLT2 (mainly in the kidney cortex), the latter of which plays an important role in glucose reabsorption; SGLT2 inhibitors (SGLT-2i), including dapa- https://doi.org/10.62347/AAPZ2726 SGLT-2 and lipid profile gliflozin, canagliflozin, and empagliflozin, can effectively control blood sugar levels; In this way, by inhibiting the sodium-glucose cotransporter in the proximal area of the nephron, while inhibiting the reabsorption of glucose in the kidneys, they increase its urinary excretion [1-3]. Additionally, these medications have a significant impact on lipid metabolism, influencing cellular processes to reduce lipid accumulation and body fat [1]. The following class of medications has been demonstrated to offer advantageous effects in safeguarding the heart and kidneys under various conditions: type 2 diabetes, chronic kidney disease, and heart failure (HF). The therapeutic advantages of SGLT-2i in individuals with heart failure were first observed in patients with a lower ejection fraction and are currently highly recommended as an essential component of comprehensive disease management [4]. Enhancing the management of diabetic dyslipidemia may potentially lead to a decrease in cardiovascular risk. SGLT-2i have a moderate but positive effect on all components of diabetic dyslipidemia, including triglycerides, highdensity lipoprotein cholesterol (HDL-C) and smalldense low-density lipoprotein (sdLDL) particles. As a result, they help reduce the cardiovascular risk associated with this type of dyslipidemia. These actions may have influenced the cardioprotective advantages of this class of medication. Conversely, SGLT-2i have been shown to cause a slight increase in the lowdensity lipoprotein (LDL-C) concentration. This increase could be linked to an elevated risk of cardiovascular issues as LDL-C is a significant determinant of cardiovascular risk [5]. The prescription of SGLT-2i has expanded beyond treating diabetes to include heart failure, since clinical studies have shown its efficacy in preventing hospitalization for heart failure in individuals with or without diabetes. SGLT-2i exhibit additional effects beyond their initial hypoglycemic response, such as diuretic, antihypertensive, hemopoietic, and inhibitory activities on sympathetic nerve activity [6]. Although several ideas have been proposed to elucidate the processes by which SGLT-2i decrease the occurrence of cardiovascular events, the precise functions of these systems remain uncertain. Multiple clinical studies have 296 repeatedly shown the efficacy of SGLT-2i, with positive results such as reduced blood sugar levels, prevention of heart failure hospitalizations, and maintenance of kidney function. However, contradictory results have been reported regarding the effectiveness of SGLT-2i in preventing heart attacks, strokes, and cardiac deaths related to atherosclerotic cardiovascular disease (ASCVD) [7]. ASCVD is (...truncated)