Effects of Zinc Supplementation on Glycemic Control, Insulin Resistance, Inflammation and Oxidative Stress in Diabetes: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Abstract

ABSTRACT Objectives Diabetes mellitus (DM) is a chronic metabolic disorder characterized by insulin resistance, impaired insulin secretion, and increased cardiometabolic and inflammatory burden. Zinc plays a key biological role in insulin synthesis, storage, signalling and antioxidant defence; however, the clinical relevance and consistency of zinc supplementation effects in diabetes remain uncertain. Methods A systematic search of PubMed/MEDLINE, Web of Science, Scopus, CINAHL and Google Scholar was conducted to identify randomized controlled trials (RCTs) assessing zinc supplementation in individuals with diabetes, gestational diabetes or prediabetes. Results Eighteen RCTs involving 1023 participants met the eligibility criteria. Zinc supplementation significantly increased plasma zinc concentrations (MD = 7.80; 95% CI 4.33 to 11.26) and improved insulin resistance, as reflected by reductions in serum insulin (MD = −2.50; 95% CI −4.69 to −0.31) and HOMA‐IR (MD = −1.10; 95% CI −2.05 to −0.15). Total cholesterol decreased modestly but significantly (MD = −5.70; 95% CI −7.50 to −3.89), representing a relatively small absolute reduction, while LDL cholesterol showed a modest increase (MD = 3.46; 95% CI 1.48 to 5.43), although the clinical relevance of this finding remains uncertain. Inflammatory and oxidative stress markers improved, including reductions in C‐reactive protein (SMD = −0.91; 95% CI −1.43 to −0.38) and malondialdehyde (SMD = −0.76; 95% CI −1.34 to −0.18), alongside an increase in total antioxidant capacity (SMD = 1.79; 95% CI 0.68 to 2.91). Conclusions Zinc supplementation was associated with improvements in insulin resistance, inflammatory status and oxidative stress markers in individuals with diabetes. Trial Registration International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42025638646