Exploring multifaceted roles of metformin in therapeutic applications, mechanistic insights, and innovations in drug delivery systems across biological contexts: a systematic review.

Metformin, a biguanide derivative, serves as a fundamental therapeutic agent in managing type 2 diabetes mellitus (T2DM) and is gaining recognition for its wider therapeutic applications, by the United Nations Sustainable Development Goal (SDG) 2030 priorities for promoting good health (SDG 3). This systematic review investigates the diverse roles of metformin, focusing on its therapeutic applications, mechanisms of action, and advancements in drug delivery systems. Employing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework and an optimised search strategy within Scopus and Web of Science databases, 33 high-quality studies were identified and classified into three primary thematic domains:(1) Therapeutic Applications, emphasising metformin's role in cancer, cardiovascular diseases, neurodegenerative disorders, and polycystic ovary syndrome (PCOS); (2) Mechanisms of Action, examining key pathways such as AMP-activated protein kinase (AMPK) activation, mitochondrial respiratory chain complex I inhibition, and gut microbiota modulation; and (3) Innovations in Drug Delivery Systems, investigating advanced strategies including nanoparticles, pH-responsive hydrogels, and microneedles to enhance metformin's bioavailability, targeted delivery, and patient adherence. This review highlights the challenges of conventional metformin administration, such as gastrointestinal side effects and absorption limitations, while discussing advancements in drug delivery technologies designed to address these issues. Implementing metformin in non-diabetic contexts faces challenges related to cost and regulatory issues. This review synthesises evidence from preclinical and clinical studies, positioning metformin as a versatile therapeutic agent for various chronic conditions and highlighting the necessity for ongoing research into its mechanisms and delivery technologies. The findings indicate that metformin may play a role in enhancing sustainable healthcare solutions by promoting health equity and advancing global health objectives, consistent with SDG 2030.