SGLT-2 inhibitors in obesity and its associated cardiometabolic disorders: where do we stand?

Abstract

As the tide of obesity and its complications is on the rise, there is an urgent need for new drugs with weight-lowering and beneficial metabolic properties. Obesity-related disorders, such as metabolic syndrome, prediabetes, type 2 diabetes mellitus (T2DM), cardiovascular disease and non-alcoholic fatty liver disease (NAFLD) make this need more than mandatory. Sodium-Glucose Co-Transporter-2 (SGLT-2) inhibitors (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin) are the latest class of agents to receive approval for the treatment of T2DM. Not long after their marketing, a wide spectrum of target organ-protective and overall beneficial health effects associated with their use began to unveil. An increasing bulk of evidence points towards that these actions are to a great degree independent of glucose lowering, which has led to the broadening of the indications of SGLT-12 inhibitors outside the frame of antihyperglycemic therapy. Additionally, their unique mode of action including an increased renal glucose excretion and hence, net energy loss could render SGLT-2 inhibitors attractive candidates for the treatment of obesity. Very few reviews in the literature have appraised holistically the therapeutic potential of SGLT-2 inhibitors in obesity and its associated complications. Herein, we synopsize the currently available evidence regarding the effects of drugs of this class on body adiposity, together with considerations which accompany their potential use with the aim of weight loss. Furthermore, we attempt an overview of their actions and future perspectives of their use with respect to a range of obesity-related disorders, which include cardiovascular, renal, as well as NAFLD, malignancy, and ovarian dysfunction.

Could exercise hormone irisin be a therapeutic agent against Parkinson’s and other neurodegenerative diseases?

“…Thus, irisin acting as myokine may present a potential protective effect on the progress of obesity-related conditions [ [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] ]. Obesity has risen significantly in recent decades, becoming a major global public health concern associated with a variety of diseases including cardiovascular disease, metabolic syndrome, insulin resistance, type 2 diabetes mellitus, cancers and dementia [ [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] ]. Current data from experiments in rodents suggest that exercise induces significant browning of inguinal WAT.…”

Perspectives in vaccines, immune response, therapeutic interventions and COVID-19

“…The high prevalence of obesity, which is characterized by adipose tissue dysregulation, and is accompanied by metabolic, nutritional and immune system derangement, has played a pivotal role in COVID-19 impact [ 3 , 4 , 5 , 6 , 7 ]. Additionally, obesity is related to multiple comorbidities such as metabolic syndrome, endocrine disorders, cardiovascular and autoimmune diseases and cancer, increasing further the risk for severe COVID-19 [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Likewise, diabetes is related to obesity, showing an increasing incidence while it increases the susceptibility to SARS-CoV-2 infection and serious complications [ 2 , 19 , 20 , 21 , 22 , 23 ].…”

The catcher in the gut: Tirzepatide, a dual incretin analog for the treatment of type 2 diabetes mellitus and obesity

“…Obesity has risen significantly in recent decades, becoming a major global public health concern that influences the likelihood and prognosis of a variety of diseases, including cardiovascular disease, metabolic syndrome, insulin resistance, Type 2 diabetes mellitus (T2DM), COVID-19, and cancer [ [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] ]. Consequently, there is an urgent need for novel medications with weight-lowering and beneficial metabolic functions [ 16 ]. Obesity is a complicated and multifactorial chronic disease, defined by a body mass index (BMI) of 30 kg/m 2 or more, characterized by an excessive accumulation of white adipose tissue (AT) and AT dysfunction [ 17 ].…”

“…Changes in lifestyle such as restricted caloric intake and enhanced physical activity are vital for reducing excess body weight; however, they are not always simple to implement or successful [ 16 , 29 ]. There are various available weight-lowering medications, including, orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion and glucagon-like peptide-1 (GLP-1) receptor agonists (liraglutide); however their use can be constrained due to side effects and limited effectiveness [ 16 , 30 , 31 ]. Bariatric surgery has a great and long-lasting weight-lowering potential, and reverses prediabetic state and T2DM in a considerable number of patients [ 16 , 32 ].…”

“…There are various available weight-lowering medications, including, orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion and glucagon-like peptide-1 (GLP-1) receptor agonists (liraglutide); however their use can be constrained due to side effects and limited effectiveness [ 16 , 30 , 31 ]. Bariatric surgery has a great and long-lasting weight-lowering potential, and reverses prediabetic state and T2DM in a considerable number of patients [ 16 , 32 ]. However, while bariatric surgery is an effective treatment for severe obesity and poorly controlled T2DM, it is often linked with serious side effects [ 32 , 33 ].…”