Sodium glucose transporter type 2 (SGLT2) molecules are found in proximal tubules of the kidney, and perhaps in the brain or intestine, but rarely in any other tissue. However, their inhibitors, intended to improve diabetes compensation, have many more beneficial effects. They improve kidney and cardiovascular outcomes and decrease mortality. These benefits are not limited to diabetics but were also found in non-diabetic individuals. The pathophysiological pathways underlying the treatment success have been investigated in both clinical and experimental studies. There have been numerous excellent reviews, but these were mostly restricted to limited aspects of the knowledge. The aim of this review is to summarize the known experimental and clinical evidence of SGLT2 inhibitors' effects on individual organs (kidney, heart, liver, etc.), as well as the systemic changes that lead to an improvement in clinical outcomes.

• Keywords
• SGLT2, SGLT2 inhibitors, chronic kidney disease, diabetes, heart failure,
• MeSH
• Diabetes Mellitus, Type 2 * drug therapy   metabolism   MeSH
• Sodium-Glucose Transporter 2 Inhibitors * pharmacology   therapeutic use   MeSH
• Glucose therapeutic use   MeSH
• Cardiovascular System * metabolism   MeSH
• Humans MeSH
• Sodium metabolism   MeSH
• Sodium-Glucose Transporter 2 metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Sodium-Glucose Transporter 2 Inhibitors * MeSH
• Glucose MeSH
• Sodium MeSH
• Sodium-Glucose Transporter 2 MeSH

AIMS: In heart failure with reduced ejection fraction (HFrEF), there is an 'obesity paradox', where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a sodium-glucose co-transporter 2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). METHODS AND RESULTS: Body mass index was examined using standard categories, i.e. underweight (<18.5 kg/m2 ); normal weight (18.5-24.9 kg/m2 ); overweight (25.0-29.9 kg/m2 ); obesity class I (30.0-34.9 kg/m2 ); obesity class II (35.0-39.9 kg/m2 ); and obesity class III (≥40 kg/m2 ). The primary outcome in DAPA-HF was the composite of worsening heart failure or cardiovascular death. Overall, 1348 patients (28.4%) were under/normal-weight, 1722 (36.3%) overweight, 1013 (21.4%) obesity class I and 659 (13.9%) obesity class II/III. The unadjusted hazard ratio (95% confidence interval) for the primary outcome with obesity class 1, the lowest risk group, as reference was: under/normal-weight 1.41 (1.16-1.71), overweight 1.18 (0.97-1.42), obesity class II/III 1.37 (1.10-1.72). Patients with class I obesity were also at lowest risk of death. The effect of dapagliflozin on the primary outcome and other outcomes did not vary by baseline BMI, e.g. hazard ratio for primary outcome: under/normal-weight 0.74 (0.58-0.94), overweight 0.81 (0.65-1.02), obesity class I 0.68 (0.50-0.92), obesity class II/III 0.71 (0.51-1.00) (P-value for interaction = 0.79). The mean decrease in weight at 8 months with dapagliflozin was 0.9 (0.7-1.1) kg (P < 0.001). CONCLUSION: We confirmed an 'obesity survival paradox' in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.

• Keywords
• Adiposity, Body mass index, Dapagliflozin, Heart failure, Obesity, SGLT2 inhibitor,
• MeSH
• Benzhydryl Compounds MeSH
• Glucosides pharmacology   MeSH
• Body Mass Index MeSH
• Humans MeSH
• Heart Failure * MeSH
• Stroke Volume MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Benzhydryl Compounds MeSH
• dapagliflozin MeSH Browser
• Glucosides MeSH