The incidence of diabetes mellitus (DM) is increasing worldwide, and there is growing interest in the potential use of natural compounds as an alternative treatment for managing DM. Several research studies have investigated the impact of saffron consumption on managing and improving metabolic profiles in patients with DM, and they have shown promising results. The study aims to systematically review and perform a meta-analysis to evaluate the potential effects of saffron and its extract on cardiometabolic indicators in diabetic and prediabetic overweight patients. We conducted a comprehensive systematic review and meta-analysis, searching PubMed, Scopus, Web of Science, Embase, and Google Scholar for all relevant studies published before April 20, 2024. We extracted weighted (WMD) or standardized (SMD) mean differences (before-after) and 95% confidence intervals (95%CI) of the outcomes and conducted meta-analyses using R. The study protocol was registered in PROSPERO (CRD42024538380). Out of the studies screened, 15 RCTs were selected for inclusion in the systematic review and meta-analysis. These studies collectively involved 869 participants, 438 in the intervention group and 431 in the control group. Notably, our results showed that saffron supplementation led to significant changes in FBS (MD: - 8.75mg/dL, 95% CI [- 14.75; - 2.76], P < 0.01), HbA1C (MD: - 0.34%, 95% CI [- 0.39; - 0.9], P < 0.01), TG (MD: - 13.28 mg/dL, 95% CI [- 22.82; - 3.75], P < 0.01), SBP (MD: - 5.33 mmHg, 95% CI [- 8.99-1.67], P = 0.04), DBP (MD: - 1.02 mmHg, 95% CI [- 3.91; 1.86], P = 0.03), AST (MD: - 1.32 IU/L, 95% CI [- 1.72, - 0.93], P < 0.01) levels in T2DM patients compared to placebo or no supplementation, indicating its potential as a therapeutic intervention. However, there was no significant effect on Insulin secretion (MD: - 0.15 µU/ml, 95% CI [- 2.1763; 1.8689], P = 0.88), HOMA (MD: - 0.35%, 95% CI [- 1.34;0.63], P = 0.48), TC (MD: - 4.86 mg/dL, 95% CI [- 9.81-0.09], P = 0.54), HDL (MD: 0.18 mg/dL, 95% CI [- 0.93; 1.29], P = 0.74), LDL (MD: - 1.77 mg/dL, 95% CI [- 5.99-2.45], P = 0.41), TNF-α (MD: - 0.34 pg/mL, 95% CI [- 0.99-0.30], P = 0.29), creatinine (MD: 2.83 mg/dL, 95% CI [2.29, 3.37], P = 0.31) and BUN (MD: - 0.44 mg/dL, 95% CI [- 1.43, 0.55], P = 0.38). Saffron may improve specific CMI indices in overweight patients with diabetes or prediabetes, including significant reductions in FBS, HbA1C, TG, SBP, and AST. However, it did not significantly affect HDL, TC, LDL, insulin secretion, HOMA, DBP, TNF-α, ALT, Cr, or BUN. Further research with more trials and extended follow-up periods is needed to confirm and expand these findings.
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