Antidiabetic Efficacy and Mechanistic Insights of Azadirachta indica: A Systematic Review and Meta-Analysis of Preclinical Evidence With Nutraceutical Applications

Abstract

Background

Diabetes mellitus is a severe metabolic disease in the world, and therefore significant research has been conducted on food-derived bioactive compounds capable of antidiabetic effects. The Azadirachta indica (neem) plant, which is widely used in traditional food and ethnomedicine, contains a variety of phytochemicals that have potential applications in nutrition as nutraceuticals.

Aims

This meta-analysis and systematic review assessed the antidiabetic effects of A. indica preparations in rodents with diabetes and more so in relevancy in terms of translation to food biochemistry, nutraceutical formulation and molecular nutrition pathway.

Methods

In accordance with PRISMA 2020, we performed a systematic search of PubMed, Scopus, Web of Science and Google Scholar to identify controlled studies on antidiabetic effects of A. indica on rodent diabetes models. The SYRCLE tool was used to determine the risk of bias. Primary outcome: improvement of fasting blood glucose (FBG). Secondary outcomes: glycated haemoglobin (HbA1c), insulin, oxidative stress biomarkers (SOD, catalase, GSH, GPx, MDA) and lipid profile parameters. Random-effects meta-analyses estimated the standardized mean differences (SMDs) using the g correction of Hedges. Duration, dose, extract type and diabetes induction method were analysed as subgroups. The I² statistics and tau-squared (τ²) were used to measure heterogeneity.

Results

The meta-analysis comprised the studies that were conducted on the different A. indica preparations in the diabetic rats. A. indica had a significant effect of reducing FBG with a pooled effect size of −6.702 (95% CI: −7.621–5.165, p = 0.001), but with high heterogeneity (I² = 92.6). A. indica had a significant pooled effect of improving oxidative stress markers, improving SOD activity (SMD = 2.222, 95% CI: 0.999 to 3.450), favourable lipid profile changes included reduced total cholesterol (SMD = −3.632, 95% CI: −4.814 to −2.450), triglycerides (SMD = −4.842, 95% CI: −6.206 to −3.477), LDL cholesterol (SMD = −3.471, 95% CI: −4.701 to −2.241) and increased HDL cholesterol (SMD = 3.280, 95% CI: 2.112 to 4.447).

Conclusion

A. indica exhibits strong nutraceutical potential for diabetes management through its multitarget actions on glycaemic control, enhancement of antioxidant defence and regulation of lipid metabolism. These effects are largely attributed to key bioactive constituents, including quercetin, nimbin and azadirachtolide, which appear to act through pathways involving AMPK activation, GLUT4 translocation and PPARγ modulation. Together, these findings provide solid preclinical support for the development of A. indica as a functional food ingredient or complementary dietary supplement aimed at improving metabolic health.