Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis.

Summary

This living NMA (869 RCTs; 493,168 participants) confirms cardiovascular and kidney benefits of SGLT-2 inhibitors, GLP-1RAs, and finerenone, with substantial weight loss from tirzepatide and several GLP-1RAs. It quantifies class-specific harms (for example, SGLT-2 inhibitor–related ketoacidosis, finerenone-related hyperkalaemia) and provides risk-stratified absolute effects via an interactive tool.

Key Findings

• SGLT-2 inhibitors, GLP-1RAs, and finerenone confer cardiovascular and kidney protection (moderate-to-high certainty).
• Tirzepatide showed the greatest mean weight loss (~8.6 kg), followed by orforglipron and multiple GLP-1RAs.
• SGLT-2 inhibitors increase genital infections and diabetic ketoacidosis; finerenone increases severe hyperkalaemia; GLP-1RAs (especially tirzepatide) increase severe GI events.
• Absolute benefits vary with baseline risk; interactive tool provides risk-stratified estimates.

Clinical Implications

Prioritize SGLT-2 inhibitors and GLP-1RAs for patients at high cardiovascular/renal risk; consider finerenone in CKD. Use risk-stratified absolute effects to tailor choices and monitor class-specific harms (e.g., ketoacidosis, hyperkalaemia).

Limitations

• Heterogeneity across trials and populations; some outcomes (e.g., neuropathy, dementia) have low/very low certainty
• Medication harms and benefits depend on baseline risk; indirectness remains for certain subgroups

Future Directions

Sustain living updates, expand subgroup analyses (e.g., HFpEF, older-old), and integrate patient-reported outcomes and cost-effectiveness with absolute risk tools.