BACKGROUND: SGLT-2 inhibitors and GLP-1 receptor agonists exhibit metabolic benefits on improving obesity, diabetes, hypertension and hyperlipidemia, but the differences between them remain unclear. We evaluated the comparative efficacy of these two agents on metabolic benefits in adults with T2DM.
METHOD: This study has searched the electronic databases from the inception of the databases up to March 30, 2025. Primary outcome was the efficacy for weight loss. Secondary outcomes included the effectiveness for HbAlevels, blood pressure, and plasma lipid levels. We conducted a Bayesian network meta-analysis. This protocol was cataloged with PROSPERO (CRD42021247584). 1c
RESULTS: 168 RCTs of 72,195 adults were deemed eligible. For losing weight, GLP-1 receptor agonists were more effective than SGLT-2 inhibitors (MD - 1.08 kg,95% CrI: - 1.78 to -0.36). In subgroup analyses, compared to SGLT-2 inhibitors, GLP-1 receptor agonists displayed a stronger weight-loss effect in subgroup of 30 kg/m ≤ BMI < 35 kg/m(- 0.95 kg, - 1.91 to - 0.01) and BMI ≥ 35 kg/m(- 1.11 kg, - 6.73 to - 4.60), while had a weaker weight-loss effect in subgroup of 25 kg/m ≤ BMI < 30 kg/m(1.33 kg, 0.79-1.83). For lowering plasma glucose, GLP-1 receptor agonists showed a stronger effect on reducing HbAlevel (- 0.38%,- 0.52 to - 0.25). For decreasing blood pressure, both GLP-1 receptor agonists (- 2.10 mmHg, - 3.66 to - 0.49) and SGLT-2 inhibitors (- 3.20 mmHg, - 4.0 to - 2.39) decreased systolic blood pressure, while only SGLT-2 inhibitors (- 1.35 mmHg, - 1.67 to - 1.01) decreased diastolic blood pressure compared to placebo. For regulating serum lipids, both GLP-1 receptor agonists (- 0.14 mmol/L, - 0.22 to - 0.08) and SGLT-2 inhibitors (- 0.12 mmol/L, - 0.18 to - 0.07) lowered triglycerides, while only GLP-1 receptor agonists lowered LDL-c level (- 0.14 mmol/L, - 0.22 to - 0.06) compared to placebo. 2 2 2 2 2 1c
CONCLUSION: Both GLP-1 receptor agonists and SGLT-2 inhibitors have been shown to confer metabolic benefits. GLP-1 receptor agonists displayed stronger effects on weight reduction for patients with obesity (BMI ≥ 30 kg/m), lowering HbAlevels and improving lipid profiles. SGLT-2 inhibitors demonstrated greater efficacy in losing weight for patients with overweight (25 kg/m2 ≤ BMI < 30 kg/m2) and decreasing blood pressure. 2 1c
REGISTRATION NUMBER: CRD42021247584. The name of the registry: PROSPERO. The URL to the registration: https://www.crd.york.ac.uk/PROSPERO/.
