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Objective Multiple trials have demonstrated the metabolic effects of sodium/glucose cotransporter 2 (SGLT2) inhibitors in patients regardless of diabetes status, and recent trials have been conducted on the combined sodium/glucose cotransporter 1 and sodium/glucose cotransporter 2 (SGLT1/SGLT2) inhibitors. Therefore, a meta‐analysis was conducted to investigate the weight reduction effects and dose‐response relationship of SGLT inhibitors and to assess the relative efficacy of SGLT1/SGLT2 inhibitors. Methods Four electronic databases (PubMed, Embase, Cochrane, and Scopus) were searched on November 21, 2020, for articles published from January 1, 2000, up to November 21, 2020. Results In total, 116 randomized‐controlled trials were included, with a combined cohort of 98,497 patients. Overall, patients had a mean weight reduction of −1.79 kg (95% CI: −1.93 to −1.66, p < 0.001) compared with placebo. This effect was observed across diabetes status, duration of follow‐up, various comorbidities, and all SGLT drug types. Mean BMI changes were −0.71 kg/m2 (95% CI: −0.94 to −0.47, p < 0.001) compared with placebo. Canagliflozin, empagliflozin, sotagliflozin, and licogliflozin showed a dose‐response relationship for mean weight change. Compared with SGLT2 inhibitors, SGLT1/SGLT2 inhibitors had a significantly larger reduction in weight. Conclusions SGLT inhibitors demonstrated weight reduction benefits in this meta‐analysis. Further studies are needed to clarify their role in weight management.

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Background and ObjectiveIn recent trials, sodium-glucose cotransporter 2 (SGLT2) inhibitors proved effective as treatment for heart failure. However, the relative efficacy of sacubitril/valsartan against SGLT2 inhibitor in patients with heart failure remains unknown. Hence, we performed a network meta-analysis to compare the effects of sacubitril/valsartan against SGLT2 inhibitors on cardiovascular outcomes in patients with heart failure. Methods Four electronic databases (PubMed, Embase, Cochrane, SCOPUS) were searched for randomised-controlled trials (RCTs) published from 1st January 2000 to 25th September 2021. Two additional systematic reviews were conducted for RCTs of enalapril and valsartan to establish a common comparator arm. Frequentist network meta-analysis models were utilised to summarise the studies. Results Twenty-five RCTs were included, comprising a combined cohort of 47,275 patients. Network meta-analysis demonstrated that compared to SGLT2 inhibitors, sacubitril/valsartan achieved a larger hazard rate reduction in the composite of heart failure hospitalisation and cardiovascular death (hazard ratio [HR]: 0.86; 95% CI 0.75-0.98), cardiovascular death (HR: 0.78; 95% CI 0.65-0.94), and a larger mean change in systolic blood pressure at 8 or more months (weighted mean difference [WMD]: − 7.08 mmHg; 95% CI − 8.28 to − 5.89). There were no significant differences in treatment effects across heart failure hospitalisation, all-cause mortality, diastolic blood pressure at 12 weeks, and systolic blood pressure at 2-4 months. In patients with heart failure with reduced ejection fraction, sacubitril/valsartan achieved a 20% hazard rate reduction for cardiovascular death compared to SGLT2 inhibitors. Conclusions In patients with heart failure, sacubitril/valsartan was demonstrated to be superior to SGLT2 inhibitors in the treatment effect for the composite of heart failure hospitalisation and cardiovascular death, cardiovascular death, and longterm blood pressure.