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]
Highlights
Overweight and obesity are major risk factors for several diseases, such as hypertension, dyslipidaemia, type 2 diabetes, cardiovascular disease, osteoarthritis, obstructive sleep apnoea, fatty liver disease cancers and other diseases [1, 2]
In the subgroup analyses of SGLT2 inhibitors, we found that the individuals in the canagliflozin and sergliflozin groups had a statistically significant reduction in body weight compared to those in the placebo group (MD: -1.26 kg, 95% confidence interval (CI): -1.70 to -0.82; mean difference (MD): -1.51 kg, 95% CI: -1.87 to -1.15, respectively), while the individuals in the dapagliflozin and remogliflozin groups had no statistically significant reduction in body weight compared to those in the placebo group (MD: -4.30 kg, 95% CI: -9.76 to 1.16; MD: -2.50 kg, 95% CI: -8.18 to 3.18, respectively)
In the subgroup analyses of SGLT2 inhibitors, we found that the individuals in the canagliflozin groups had a statistically significant reduction in body mass index (BMI) compared to those in the placebo group (MD: -0.47 kg/m2, 95%CI: -0.63 to -0.31), while the individuals in the dapagliflozin, remogliflozin and sergliflozin groups had no statistically significant reduction in BMI (MD: -0.10 kg/m2, 95% CI: -1.89 to 1.69; MD: -0.70 kg/m2, 95% CI: -1.69 to 0.29; MD: -0.30 kg/m2; 95% CI: -1.26 to 0.66, respectively)
Summary
Overweight and obesity are major risk factors for several diseases, such as hypertension, dyslipidaemia, type 2 diabetes, cardiovascular disease, osteoarthritis, obstructive sleep apnoea, fatty liver disease cancers and other diseases [1, 2]. Moderate weight loss (5% of body weight) can improve glycaemic control and insulin homeostasis and mitigate cardiovascular risk factors associated with overweight and obesity [3]. Clinical practice guidelines have recommended lifestyle interventions such as diet, exercise, and behavioural modification for weight management. Bariatric surgery and/or pharmacological treatment have been recommended based on lifestyle interventions. Sodium-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. The efficacy and safety on weight loss in adults with overweight or obesity but not diabetes remain unclear. 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)
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