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SGLT-2i, GLP-1RA, finerenone, and tirzepatide deliver the strongest cardiovascular, kidney, and weight-loss benefits in adults with type 2 diabetes, while each drug class carries distinct, clinically relevant safety risks.
A systematic review and network meta-analysis provides the most comprehensive and up-to-date comparison of medications for adults with type 2 diabetes (T2D), evaluating both clinical benefits and treatment-related harms across a vast evidence base.
Kailei Nong and other researchers analyzed 869 randomized controlled trials involving 493,168 volunteers, incorporating 53 new trials added since October 2022. The review assessed 13 drug classes (63 individual drugs) across 26 clinically relevant outcomes. Evidence was generated via frequentist random-effects network meta-analysis and categorized via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework, with updates planned at least twice yearly. Searches of Medline and Embase were current up to 31 July 2024, and included trials with a minimum follow-up of 24 weeks.
The analysis provided moderate-to-high certainty evidence that:
(a) Tirzepatide showed the largest reduction in body weight (mean difference −8.63 kg; moderate certainty).
(b) Orforglipron followed closely (−7.87 kg; low certainty).
(c) 8 additional GLP-1RAs demonstrated meaningful weight reduction with high to moderate certainty.
Importantly, the absolute CV and kidney benefits varied widely depending on the patient’s baseline risk. To support personalised decision-making, the authors offered risk-stratified absolute effects through an interactive multiple-comparisons tool. The review also highlighted vital drug-class–specific safety signals:
1. SGLT-2i
2. Tirzepatide and GLP-1RAs
3. Finerenone
4. Thiazolidinediones
5. Sulfonylureas, insulin, and dipeptidyl peptidase 4 (DPP-4) inhibitors
Evidence for impact on microvascular and neurological complications, including neuropathy and visual dysfunction, remained low to very low certainty. Despite growing interest, the analysis finds uncertain evidence that GLP-1RAs diminish dementia risk (OR 0.92; low certainty). This large living evidence synthesis delivers a clear, comparative picture of CV, kidney, and weight-loss benefits, alongside important safety trade-offs, for modern T2D pharmacotherapy.
BMJ
Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis
Kailei Nong et al.
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