Comparative Efficacy and Safety of GLP-1 Receptor Agonists in Neurological and Nephrological Outcomes of Type 2 Diabetes: A Systematic Review and Network Meta-Analysis

IntroductionType 2 diabetes (T2D) is associated with significant neurological and nephrological complications, leading to high morbidity and mortality. GLP-1 receptor agonists (GLP-1 RAs), such as liraglutide, semaglutide, and tirzepatide, have been shown to effectively control glycemia, with additional neuroprotective and nephroprotective effects. This systematic review and network meta-analysis (NMA) aimed to evaluate the impact of GLP-1 RAs on neurological and nephrological outcomes in T2D patients. MethodsA literature search was conducted across PubMed, Cochrane, and ClinicalTrials.gov for randomized controlled trials (RCTs) published between 2010 and 2023. Studies were included if they evaluated the effects of GLP-1 RAs on neurological and nephrological outcomes in T2D patients. A total of 17 studies, involving 96,460 patients (60,190 males, 36,199 females, average age 62.99 {+/-} 7 years), were selected. Network meta-analysis was performed to compare the efficacy and safety of different GLP-1 RAs on outcomes such as neuropathy, cognitive function, albuminuria, and glomerular filtration rate (GFR). ResultsAmong the 17 studies, GLP-1 RAs showed significant improvements in neurological and nephrological outcomes. Neurological benefits included a 24% improvement in cognitive function and a 31% reduction in neuropathic pain. Nephrological benefits included a 27% reduction in albuminuria and a 19% improvement in GFR. Tirzepatide demonstrated the most significant renal improvement, with a mean difference in GFR of 2.50 (95% CI: 0.36, 4.64). Subgroup analyses showed consistent efficacy across age, gender, and ethnicity, with no significant differences in treatment effects. Adverse events were generally mild, with gastrointestinal issues (nausea, vomiting) occurring in 11% of patients, but discontinuation rates were low (5%). ConclusionGLP-1 RAs significantly improve both neurological and nephrological outcomes in T2D patients. While variability in effects exists, these agents offer substantial benefits in managing T2D complications, with a favorable safety profile.