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Sodium-glucose cotransporter 2 inhibitors (SGLT-2) are a new class of hypoglycemic drugs that were initially approved for the treatment of type 2 diabetes. Currently, 5 drugs in the SGLT-2 class of drugs are approved by the FDA for glycemic control: canagliflozin, dapagliflozin, empagliflozin, ertugliflozin and sotagliflozin. However, their effectiveness in reducing the risk of heart failure and progression of chronic kidney disease was soon established, regardless of diabetes status. In addition, according to a number of meta-analyses of RCTs in patients with cardiometabolic and renal diseases, the use of SGLT-2 reduces cardiovascular and overall mortality and the number of serious adverse cardiac events and renal outcomes in patients with or without diabetes, which is reflected in the indications to their use. Scientific data are presented in a discussion of the mechanisms of cardioprotective and renoprotective effects of the SGLT-2 class, many of which are considered as pleiotropic effects not related to the effect on glycemic levels.

Type 2 diabetes is characterized by increasing incidence and prevalence all-over the world. Current therapeutic management of type 2 diabetes is complex and is based not only on glycemic control, but also on cardiovascular and renal risks reduction. In previous years the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) increased in Russian Federation. Some manufacturers of the most widely used GLP-1 RA reported the supply decline in several countries. On Advisory board with participation of the Russian Endocrinology Association members the topics of SGLT2i and GLP-1 RA use in type 2 diabetes were discussed. The experts made conclusion that the decrease in access to GLP-1 RA does not pose serious risk for treatment of type 2 diabetes patients. SGLT2i show benefits in risk reduction of HF and CKD progression compering to GLP-1 RA, and in general show comparable efficacy in risk reduction of ACVD outcomes. SGLT2i show less glycemic efficacy in comparison with GLP-1 RA, and their replacement may need adding antidiabetic agents from other groups.

The findings of large-scale cardiovascular outcome trials have been demonstrated that sodium-glucose cotransporter 2 ­inhibitors (iSGLT-2) have shown beneficial cardiovascular effects. In this review proposed mechanisms underlying iSGLT-2-associated cardiovascular benefits have been discussed: haemodynamic and intracellular effects, including metabolic effects and electrolyte changes; and also, the effect on markers of cardiovascular disease (CVD). The hemodynamic effects of SGLT-2 are characterized by reduction of cardiac preload and afterload as a result of osmotic diuresis, a decrease in blood pressure and arterial stiffness. The metabolic effects of this medicine are accompanied by an increase the production of ketone bodies, followed by improving ATP production and myocardial energetics. Also, iSGLT-2 modulate ion transporters (NHE1 and NHE3). A reduction of cytoplasmic sodium and calcium levels and increasing mitochondrial calcium levels in the cardiomyocytes enhances the synthesis of ATP and increases cell viability. Effect of iSGLT-2 on CVD markers showed a decrease in the levels of the N-terminal pro-B-type natriuretic peptide and highly sensitive troponin I in elderly patients with type 2 diabetes mellitus (T2DM). Thus, this class of agents has a multifactorial effect on the functioning of cardiovascular system. Further studies will help to explain the all possible cardioprotective effects of iSGLT-2 in individuals with and without T2DM.

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Pathology of bone homeostasis in diabetes mellitus (DM) is a significant problem that must be considered when selecting anti-diabetic therapy. Many anti-diabetic drugs have a specific effect on bone homeostasis which should be taken into account when selecting treatment for type 2 diabetes, especially in patients at high risk of osteoporosis. This review discusses mechanisms of impact on bone metabolism and fracture risks of DM and various groups of antidiabetic drugs, focusing on new groups of drugs included in the Russian algorithms over the past decade (GLP-1 receptor agonists, DPP-4 inhibitors, sodium-glucose cotransporter 2 inhibitors). It can be useful to both researchers and clinicians who are striving to offer the therapy of choice to their patients today.