In a study, researchers aimed to evaluate how age and sex influence the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase 4 (DPP4) inhibitors in managing hyperglycemia and reducing major adverse cardiovascular events (MACEs) in individuals with type 2 diabetes. The analysis included 601 trials with over 309,000 participants, assessing both HbA1c reduction and MACEs. Results showed that SGLT2 inhibitors provided less HbA1c reduction with increasing age across all therapy regimens, whereas GLP-1 receptor agonists resulted in greater HbA1c lowering with age for monotherapy and dual therapy, but not for triple therapy. DPP4 inhibitors showed slightly better HbA1c lowering in older individuals, especially for dual therapy. Additionally, SGLT2 inhibitors were more effective in reducing the risk of MACEs in older participants, while GLP-1 receptor agonists had a stronger effect in younger participants.

The findings suggest that SGLT2 inhibitors and GLP-1 receptor agonists are both effective in reducing the risk of MACEs, but their efficacy may differ based on age. SGLT2 inhibitors are more cardioprotective in older patients despite a smaller reduction in HbA1c, whereas GLP-1 receptor agonists offer more cardioprotection in younger individuals. The authors did not find consistent evidence of sex-related differences in treatment efficacy, providing reassurance that the observed effects were not significantly influenced by gender. These results underscore the importance of considering age when selecting diabetes treatments that also reduce cardiovascular risk.

Reference: Hanlon P, Butterly E, Wei L, et al. Age and Sex Differences in Efficacy of Treatments for Type 2 Diabetes: A Network Meta-Analysis. JAMA. 2025;333(12):1062-1073. doi: 10.1001/jama.2024.27402.