Mechanistic insights into psoriasis and type 2 diabetes mellitus comorbidity – Implications for treatment: A review

Psoriasis is a chronic systemic inflammatory disease primarily affecting the skin, yet it is increasingly recognized for its systemic implications, particularly its strong association with type 2 diabetes mellitus (T2DM). This review synthesizes recent mechanistic and clinical evidence to elucidate the shared pathways linking psoriasis and T2DM, as well as to explore therapeutic strategies for this comorbidity. We conducted a narrative review of studies published between January 2020 and October 2025, encompassing preclinical models, clinical trials, and high-quality reviews that address pathogenesis and treatment. Key findings indicate that shared genetic loci and molecular pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, the IL-23/Th17 axis, and mitochondrial dysfunction associated with the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, contribute to both cutaneous inflammation and systemic metabolic dysregulation. Additionally, adipokine imbalances and chronic low-grade inflammation exacerbate insulin resistance and psoriatic skin pathology. Therapeutically, IL-17/IL-23 inhibitors, metformin, glucagon-like peptide 1 (GLP-1) receptor agonists, and other immunomodulatory strategies demonstrate potential in addressing both dermatologic and metabolic features. These insights reinforce the notion of psoriasis as a systemic disorder with significant metabolic consequences, highlighting the need for integrated, multidisciplinary management. Future research should concentrate on precise gene-environment interactions, biomarker validation, and the development of treatments that simultaneously target both skin and metabolic pathology to advance precision medicine for patients with psoriasis-T2DM comorbidity.