Mediterranean diet for the management of pre-existing metabolic diseases: Evidence from a systematic review and meta-analysis featured in the Italian national guidelines “La Dieta Mediterranea”

Background: Metabolic diseases such as obesity, type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, and non-alcoholic fatty liver disease are major contributors to cardiometabolic risk. While the Mediterranean diet (MD) is well-established in primary prevention, its role in individuals with pre-existing metabolic conditions remains less defined. Methods: A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 2020 and Meta-analysis of Observational Studies in Epidemiology guidelines. PubMed, Scopus, Embase, and Cochrane Library were searched through February 2024. Study quality was assessed using the Newcastle-Ottawa Scale; evidence certainty was evaluated with the NUTRIGRADE tool. Random-effects models were used to pool effect sizes. Results: Sixty-nine studies were included. Higher adherence to the MD was associated with reduced all-cause mortality in individuals with type 2 diabetes or metabolic syndrome (risk ratios: 0.93; 95% CI: 0.90-0.97). Moderate-quality evidence supported improvements in BMI, waist circumference, LDL cholesterol, triglycerides, fasting glucose, HOMA-IR, and C-reactive protein. Findings for HDL cholesterol, lean mass, and HbA1c were inconsistent. One RCT reported improved quality of life, while evidence on gut microbiota modulation remains very limited and largely descriptive. Overall, evidence certainty ranged from moderate to low. Conclusions: Greater adherence to the MD is linked to modest but clinically relevant improvements in metabolic health and reduced mortality in individuals with existing metabolic diseases. These findings support its inclusion in therapeutic dietary strategies, though further high-quality, long-term trials are needed to inform clinical guidelines.