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 HbA1c levels, blood pressure, and plasma lipid levels. We conducted a Bayesian network meta-analysis. This protocol was cataloged with PROSPERO (CRD42021247584). 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/m2 ≤ BMI < 35 kg/m2 (− 0.95 kg, − 1.91 to − 0.01) and BMI ≥ 35 kg/m2 (− 1.11 kg, − 6.73 to − 4.60), while had a weaker weight-loss effect in subgroup of 25 kg/m2 ≤ BMI < 30 kg/m2 (1.33 kg, 0.79–1.83). For lowering plasma glucose, GLP-1 receptor agonists showed a stronger effect on reducing HbA1c level (− 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. 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/m2), lowering HbA1c levels 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. Registration number: CRD42021247584. The name of the registry: PROSPERO. The URL to the registration: <a href="https://www.crd.york.ac.uk/PROSPERO/">https://www.crd.york.ac.uk/PROSPERO/</a>.

The comparative efficacy of SGLT-2 inhibitors and GLP-1 receptor agonists on metabolic benefits in T2DM patients: a systematic review and network meta-analysis

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2026年1月31日

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Jingkai Tong,
Nana Li,
Fang Hu,
Yingying Yue

摘要

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 HbA_1c levels, blood pressure, and plasma lipid levels. We conducted a Bayesian network meta-analysis. This protocol was cataloged with PROSPERO (CRD42021247584).

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/m² ≤ BMI < 35 kg/m² (− 0.95 kg, − 1.91 to − 0.01) and BMI ≥ 35 kg/m² (− 1.11 kg, − 6.73 to − 4.60), while had a weaker weight-loss effect in subgroup of 25 kg/m² ≤ BMI < 30 kg/m² (1.33 kg, 0.79–1.83). For lowering plasma glucose, GLP-1 receptor agonists showed a stronger effect on reducing HbA_1c level (− 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.

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/m²), lowering HbA_1c levels 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.

Registration number: CRD42021247584. The name of the registry: PROSPERO. The URL to the registration: https://www.crd.york.ac.uk/PROSPERO/.