Effectiveness of ω-3 Supplementation on Biochemical, Clinical, and Inflammatory Parameters in Patients with Diabetes: A Systematic Review and Meta-analysis

Background and objectives Omega-3 polyunsaturated fatty acids, including marine-derived EPA and DHA as well as plant-derived formulations rich in α-linolenic acid, have been proposed as adjunctive therapy in diabetes because of their potential effects on lipid metabolism, inflammation, oxidative stress, and neuroprotection. Methods Searches were performed in MEDLINE, EMBASE, SCOPUS, CENTRAL, CINAHL, and Web of Science through January 2026. Outcomes included lipid parameters, glycemic markers, inflammatory and oxidative stress biomarkers, and corneal nerve branch density (CNBD). Random-effects models were applied. Eleven trials met the criteria for quantitative synthesis. Pooled analyses showed no significant effects on triglycerides, LDL or HDL cholesterol, HbA1c, fasting plasma glucose, or inflammatory and oxidative stress biomarkers, with substantial heterogeneity across several outcomes. In contrast, fasting insulin and HOMA-IR were significantly reduced with low heterogeneity, and CNBD showed a consistent improvement with no detectable heterogeneity, suggesting potential benefits for insulin sensitivity and small-fiber nerve integrity. Overall, the certainty of evidence ranged from very low to low, mainly due to heterogeneity, imprecision, and small sample sizes. Conclusions Omega-3 supplementation demonstrated limited effects on most metabolic and inflammatory outcomes in diabetes. Observed improvements in insulin sensitivity indices and CNBD warrant further investigation in adequately powered trials with longer follow-up. These findings should be interpreted as hypothesis-generating rather than confirmatory. New clinical relevance The improvements observed in insulin sensitivity indices and in CNBD have not been reported in previous meta-analyses that have linked diabetes mellitus with Omega-3