Sodium-Glucose Co-Transporter-2 Inhibitors in Non-Diabetic Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis

Abstract

BackgroundSodium-glucose-cotransporter-2 (SGLT2) inhibitors have proven to be effective in improving glycemic control and lowering body weight in patients with type 2 diabetes mellitus. However, the efficacy and safety on weight loss in adults with overweight or obesity but not diabetes remain unclear. In this article, we aimed to identify the efficacy and safety of SGLT2 inhibitors in adults with overweight or obesity but not diabetes in randomized controlled studies (RCTs).MethodsWe searched for RCTs concerning SGLT2 inhibitors in adults with overweight or obesity but not diabetes in Medline (Ovid SP), Embase (Ovid SP), Cochrane Central Register of Controlled Trials (Ovid SP), and ClinicalTrials.gov up to February 2021. The primary outcomes were changes in body weight and body mass index (BMI). Trial sequential analysis (TSA) was used to test the reliability of the primary outcomes. We analyzed the data using Review Manager 5.3 and pooled data to calculate the mean differences (MDs) or the relative risk (RR). We assessed the evidence quality of evidence of outcomes according to GRADE.ResultsSix randomized controlled trials involving 872 individuals were included in the meta-analysis. Compared to the placebo group, the SGLT2 inhibitors group had statistically significant reductions in absolute changes in body weight (MD: -1.42 kg, 95% CI: -1.70 to -1.14; P<0.00001) and BMI (MD: -0.47 kg/m2, 95% CI: -0.63 to -0.31; P<0.00001) in SGLT2 inhibitors group, as indicated by TSA. However, no significant benefits were observed in the SGLT2 inhibitors group in terms of waist circumference (MD: -1.34 cm, 95%CI: -2.75 to 0.07; Z=1.86, P=0.06) compared with the placebo group. The GRADE profiles indicated very low-quality evidence for body weight change and low-quality evidence for BMI change. SGLT2 inhibitors were generally safe and well tolerated.ConclusionSGLT2 inhibitors could be used in selected adults with overweight and obesity but not diabetes if they are at low risk of genital infection and urinary infection. Further studies are warranted to confirm the efficacy and safety of SGLT2 inhibitors in adults with overweight or obesity but not diabetes for long-term weight management.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/#loginpage], identifier [PROSPERO, CRD42021252931]

Effects and mechanisms of SGLT2 inhibitors on the NLRP3 inflammasome, with a focus on atherosclerosis

“…It has been shown that SGLT2 inhibitors can act directly on inflammatory pathways independent of hypoglycemic pathways ( 111 ). SGLT2 inhibitors are safe and well tolerated in adults who are overweight and obese but do not have diabetes ( 122 ). Under normal glucose conditions, SGLT2i inhibits SMC migration and proliferation by targeting il-17a-mediated oxidative stress, NLRP3 expression and inflammatory responses without inducing cell death ( 123 ).…”

Sodium–glucose cotransporter 2 inhibitors in horses—Magic bullet or latest fad?

“…pressure. 1,2 Beneficial effects have also been reported in renal and cardiovascular disease, [3][4][5][6][7][8] and human use has increased considerably both in diabetic and non-diabetic patients in response to a growing body of evidence of clinical benefit. 9 Canagliflozin was the first SGLT2i registered for use in people in 2013 and was followed by others including dapagliflozin, empagliflozin and most recently, ertugliflozin.…”

“…Sodium–glucose cotransporter 2 inhibitors (SGLT2i) were initially developed as a new class of human antidiabetic medications that lower insulin concentrations, promote weight loss and reduce blood pressure 1,2 . Beneficial effects have also been reported in renal and cardiovascular disease, 3–8 and human use has increased considerably both in diabetic and non‐diabetic patients in response to a growing body of evidence of clinical benefit 9 . Canagliflozin was the first SGLT2i registered for use in people in 2013 and was followed by others including dapagliflozin, empagliflozin and most recently, ertugliflozin 10 .…”

Review of Prediabetes

“…The weight-reduction benefits of SGLT2 inhibitors as the mainstay of prediabetes management have been reported in multiple RCTs. A systematic review and meta-analysis of 6 RCTs with 872 adults with overweight or obesity without diabetes demonstrated that SGLT2 inhibitors significantly reduced absolute changes in body weight (−1.42 kg; 95% CI, −1.70 to −1.14 kg) and body mass index (−0.47; 95% CI, −0.63 to −0.31). Based on available evidence, SGLT2 inhibitors may be considered in treatment of prediabetes.…”