Impact of agonists of glucagon-like peptide-1 receptor in individuals with type 2 diabetes: A meta-analysis

Abstract

Mohamed S. Imam*, Fahad Saeed Algahtani, Naif Ayidh Alshabab, Manar Mesfer Eid Alsaadi, Mastora Shajea Falaj Alotaibi, Azoof Abdullah Naqi Alotaibi, Abdulrahman Abdullah Zaben Alnefaie, Retaj Awad AlNafie, Raghad Khaled Alzahrani, Sultan Ali A. Alqahtani, Saeed Hussain Saeed Alzahrani, Nawaf Mohammed A. Alhossan, Latifa Fahad Abdalwahap Almohsin, Ahmed Khalid Almutairi and Randa M. Abdel-Sattar

Background and objectives: We have done a meta-analysis to assess influence of glucagon-like peptide-1 receptor agonists (GLP1RAs) in individuals with Type 2 Diabetes Mellitus (T2DM). Beyond clinical relevance, GLP1RAs act through metabolic pathways that may also be influenced by plant-derived bioactive compounds, suggesting possible phytotherapeutic implications.

Materials and methods: A thorough literature search conducted till January 2025 identified 10 studies encompassing 1,639,510 patients with T2DM at study’s inception. Study reported correlations between effects of Impact of GLP1RAs in individuals with T2DM. We computed Odds Ratio (OR) with 95% Confidence Intervals (CIs) to evaluate impact of Impact of GLP1RAs in individuals with T2DM, employing dichotomous method with either a random or fixed-effect model.

Results: GLP1RAs demonstrated significantly reduced all-cause mortality (OR, 0.77; 95% CI, 0.66-0.90, p<0.001), cardiovascular mortality (OR, 0.87; 95% CI, 0.81-0.94, p<0.001), myocardial infarction (OR, 0.92; 95% CI, 0.85-0.98, p=0.01), stroke (OR, 0.87; 95% CI, 0.83-0.91, p<0.001), hospital admissions owing to heart failure (OR, 0.86; 95% CI, 0.74-1.00, p=0.05), and renal events (OR, 0.83; 95% CI, 0.77-0.89, p<0.001), as well as a composite kidney outcome including macroalbuminuria (OR, 0.86; 95% CI, 0.83-0.89, p<0.001) and deterioration of kidney function (OR, 0.83; 95% CI, 0.74-0.93, p=0.002) when compared to placebo in individuals with T2DM. No significant difference was detected between GLP1RAs and placebo regarding ocular events (OR, 1.18; 95% CI, 0.91-1.54, p=0.21) and
three-component major adverse cardiovascular events (OR, 0.99; 95% CI, 0.65-1.51, p=0.95) in individuals with T2DM.

Conclusion: GLP1RAs were associated with significantly reduced all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, hospital admissions for heart failure, and renal events, as well as a composite kidney outcome including macroalbuminuria and deterioration of kidney function. Yet, no significant differences were detected in ocular events and three-component major adverse cardiovascular events when compared to placebo in individuals with T2DM. Importantly, these findings highlight incretin-based mechanisms as potential targets for plant-derived compounds (e.g., flavonoids, alkaloids, and terpenoids) that can modulate glucose homeostasis. Future research should integrate phytochemical screening and phytomorphological studies to identify natural agents with
GLP1RA-like activity.