SGLT2 Inhibitors and the Mechanisms Involved in Weight Loss
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CLINICAL PHARMACOLOGY (L BRUNETTI, SECTION EDITOR)
SGLT2 Inhibitors and the Mechanisms Involved in Weight Loss David Feder 1 & Marisa Regina de Fatima Veiga Gouveia 1 & Tania Carmen Peñaranda Govato 1 & Cristina De Zotti Nassis 1
# Springer Nature Switzerland AG 2020
Abstract Purpose of Review To study the mechanisms of weight loss with inhibitors of SGLT2 receptors. SGLT2 inhibitors are a new class of drugs used in the treatment of type 2 diabetes mellitus (T2DM). These drugs inhibit the SGLT2 receptor in the proximal tubule, responsible for 90% of renal glucose reabsorption. Recent Findings SGLT2 inhibitor treatments can result in an average reduction in body weight between 2 and 4 kg; this reduction is consistent in all studies, for all molecules, either as monotherapy or in combination with other antidiabetic drugs. It is observed that weight loss is maintained for up to 4 years. Among the mechanisms proposed for weight loss are urinary glucose loss, alteration of the insulin/glucagon ratio with increased lipolysis, activation of the AMPK enzyme, inhibition of mTORC1, improvement of mitochondrial function, polarization of macrophages from M1 to M2, browning adipose tissue, leptin inhibition and increased adiponectin expression, and activation of FGF-21 expression. Summary Despite the numerous mechanisms proposed for weight loss with SGLT2 inhibitors, lipolysis seems to be the central point of all of them. It is necessary to establish how these mechanisms interact, the chronology of these changes, which one is the most important for weight loss, and how these mechanisms can contribute to the cardiovascular benefits of SLGT2 inhibitor therapy. Keywords SGLT2 . SGLT2 inhibitors . Obesity . Diabetes mellitus . Weight loss
Introduction Type 2 diabetes mellitus (T2DM) is a disease with an increasing incidence, affecting about 387 million people worldwide [1]. Obesity is an important risk factor for the development of insulin resistance and T2DM and its control is a major treatment goal [2]. Obesity, as well as insulin resistance and other metabolic disorders, is associated with chronic inflammation, characterized by the abnormal production of cytokines [3]; these are all risk factors for cardiovascular atherosclerotic disease. According to the World Health Organization, 40% of the population was obese or overweight in 2016 [4••]. Inhibitors of SGLT2 receptors are a new class of drugs used in the treatment of T2DM [5••]. With a mechanism of action independent of secretion and sensitivity to insulin, This article is part of the Topical Collection on Clinical Pharmacology * David Feder [email protected] 1
Department of Pharmacology, Centro Universitario Saude ABC, Santo Andre, SP, Brazil
these drugs inhibit the SGLT2 receptor in the proximal tubule, responsible for 90% of renal glucose reabsorption [5••]. Clinical studies have shown that this group of drugs improves diabetes control, lowers blood pressure, decreases cardiac risk and contributes to weight loss [6••]. The purpose of this review is to study the mec
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