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      Empagliflozin Ameliorates Progression From Prediabetes to Diabetes and Improves Hepatic Lipid Metabolism: A Systematic Review

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          Abstract

          Diabetes mellitus (DM) and hepatic steatosis are two of the most common metabolic syndromes that affect the health of people globally. Empagliflozin (EMPA) is a promising drug of choice for the diabetic population. Recent studies have shown its beneficial effects not only on diabetic patients but also on patients suffering from cardiac, hepatic, neurological, or pancreatic anomalies. In this paper, we systematically searched electronic databases to compile literature that focuses on EMPA’s effect on the prediabetic population, diabetic population, and hepatic lipid metabolism. We focus on the mechanism of EMPA, specifically by which it increases insulin sensitivity and fat browning and reduces fat accumulation. Overall, we hypothesized that by its effect on weight loss and reducing inflammatory markers and insulin resistance (IR), EMPA decreases the rate of prediabetes to diabetes conversion. We concluded that by improving hepatic and serum triglyceride, decreasing visceral fat, and its positive impact on hepatic steatosis, the drug improves hepatic lipid metabolism. Further research should be done on this matter.

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          SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and Browning and Attenuates Inflammation and Insulin Resistance by Polarizing M2 Macrophages in Diet-induced Obese Mice

          Sodium-glucose cotransporter (SGLT) 2 inhibitors increase urinary glucose excretion (UGE), leading to blood glucose reductions and weight loss. However, the impacts of SGLT2 inhibition on energy homeostasis and obesity-induced insulin resistance are less well known. Here, we show that empagliflozin, a SGLT2 inhibitor, enhanced energy expenditure and attenuated inflammation and insulin resistance in high-fat-diet-induced obese (DIO) mice. C57BL/6J mice were pair-fed a high-fat diet (HFD) or a HFD with empagliflozin for 16 weeks. Empagliflozin administration increased UGE in the DIO mice, whereas it suppressed HFD-induced weight gain, insulin resistance, and hepatic steatosis. Moreover, empagliflozin shifted energy metabolism towards fat utilization, elevated AMP-activated protein kinase and acetyl-CoA carbolxylase phosphorylation in skeletal muscle, and increased hepatic and plasma fibroblast growth factor 21 levels. Importantly, empagliflozin increased energy expenditure, heat production, and the expression of uncoupling protein 1 in brown fat and in inguinal and epididymal white adipose tissue (WAT). Furthermore, empagliflozin reduced M1-polarized macrophage accumulation while inducing the anti-inflammatory M2 phenotype of macrophages within WAT and liver, lowering plasma TNFα levels and attenuating obesity-related chronic inflammation. Thus, empagliflozin suppressed weight gain by enhancing fat utilization and browning and attenuated obesity-induced inflammation and insulin resistance by polarizing M2 macrophages in WAT and liver.
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            Randomized Trial of Empagliflozin in Non-Diabetic Patients with Heart Failure and Reduced Ejection Fraction

            Large clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia.
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              Effect of Empagliflozin on Cardiovascular and Renal Outcomes in Patients With Heart Failure by Baseline Diabetes Status

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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                25 August 2022
                August 2022
                : 14
                : 8
                : e28367
                Affiliations
                [1 ] Hospital Medicine, Upazila Health Complex, Kishoreganj, BGD
                [2 ] Pediatric, Caribbean Medical University, Chapel Hill, USA
                [3 ] Hospital Medicine, Satkhira Medical College, Satkhira, BGD
                [4 ] Hospital Medicine, Sylhet MAG (Muhammad Ataul Goni) Osmani Medical College Hospital, Sylhet, BGD
                [5 ] Internal Medicine, Sher-E-Bangla Medical College, Barishal, BGD
                [6 ] Internal Medicine, Sylhet MAG (Muhammad Ataul Goni) Osmani Medical College Hospital, Sylhet, BGD
                [7 ] Internal Medicine, Sir Salimullah Medical College, Dhaka, BGD
                [8 ] Internal Medicine, Comilla Medical College Hospital, Chittagong, BGD
                [9 ] Hospital Medicine, Sacramento VA (Veterans Affairs) Medical Center, Mather, USA
                Author notes
                Article
                10.7759/cureus.28367
                9506669
                36168335
                9b3adcea-25b5-4a36-a44f-272185d3e29a
                Copyright © 2022, Hossain et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 August 2022
                Categories
                Endocrinology/Diabetes/Metabolism
                Internal Medicine
                Therapeutics

                obesity,hepatic steatosis,insulin resistance,hepatic lipid metabolism,non-alcoholic steatohepatitis (nash),pre-diabetic and non-diabetic,non-alcoholic fatty liver disease (nafld),sglt 2 inhibitor,empa

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