<p>Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence</p>

Abstract

Patients with type 2 diabetes (T2D) are often overweight/obese and affected by arterial hypertension, dyslipidaemia, and have high serum levels of uric acid. Moreover, T2D patient have a higher risk of developing cardiovascular or renal complications, which are leading causes of morbidity and mortality in this population. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a new class of glucose-lowering medications that block the reabsorption of glucose in the kidney, thereby increasing urinary glucose excretion, and lowering blood glucose levels. The beneficial effects of SGLT2 inhibition extend beyond glycaemic control, and include improvement in blood pressure, body weight, uric acid concentrations, liver steatosis, oxidative stress, and inflammation. In dedicated cardiovascular outcome trials, SGLT2i treatment was associated with a significant reduction in the rate of cardiovascular events and renal endpoints. In this review, we summarize the evidence for extra-glycemic effects of SGLT2i and the potential mechanisms driving cardiorenal protection exerted by this class of medications.

Repurposing existing drugs for COVID-19: an endocrinology perspective

“…Sodium-glucose Co-transporter 2 inhibitors (SGLT2i) (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin) are a newly developed anti-diabetic drug class that promotes glycosuria through inhibition of renal glucose reabsorption, alleviating hyperglycemic states. Unexpected improvements of cardiovascular events, overall mortality, liver metabolic dysfunctions, kidney function, and pancreas activity observed in larger and longer randomized clinical trials (RCTs) and reallife studies were not completely justifiable by its glucose-, body weight-, and blood pressure-lowering effects [296][297][298]. Although effects on overall viral replication or lung injury are yet to be unraveled, SGLT2i's have shown active suppression of the overall RAAS due to the negative water balance induced by its concurrent natriuresis, and additional selective mitigation of the angiotensin II-AT1R axis [299][300][301][302].…”

Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis

“…The SLGT2 inhibitors reduced the risk for a major cardiac event by 11% (hazard ratio, 0.89; 95% CI, 0.83-0.96) in patients with CVD. [126,127]. Metanalysis of seven randomized controlled trials of GLP-1 agonists versus placebo shows that the treatment was associated with a significant 12% lower risk for MACE (cardiovascular death, stroke, or myocardial infarction), a 12% reduction in all-cause mortality risk, and a significant 9% reduction in rates of hospitalization for heart failure [128,129].…”

SGLT2 is not expressed in pancreatic α- and β-cells, and its inhibition does not directly affect glucagon and insulin secretion in rodents and humans

“…SGLT2 inhibitors (SGLT2i), called gliflozins, decrease glycemia by blocking glucose reabsorption by the kidney, thus promoting glucosuria. They are extensively used to treat diabetes and exert other beneficial effects such as improvement of insulin sensitivity and β-cell function, cardiorenal protection, and weight loss [ [1] , [2] , [3] , [4] , [5] , [6] , [7] ]. SGLT2i-induced glucosuria is associated with metabolic responses, including an increase in lipolysis, endogenous glucose, and ketone body production [ 3 , 8 , 9 ].…”