International Journal of Scientific Research and Engineering Development

Type 2 diabetes mellitus (T2DM) represents a major global health challenge, affecting over 500 million adults worldwide and contributing significantly to cardiovascular morbidity and mortality. Metformin has remained the cornerstone of T2DM management for decades, maintaining its position as the recommended first-line therapy in international treatment guidelines. This review comprehensively examines metformin's evolving role from its historical origins to contemporary applications and future directions. Initially derived from Galega officinalis (French lilac), metformin's mechanism primarily involves AMP-activated protein kinase (AMPK) activation and hepatic gluconeogenesis suppression, though emerging research continues to reveal additional molecular targets. The drug's enduring preference stems from its favorable efficacy-safety profile, cost- effectiveness, weight-neutral properties, and proven cardiovascular benefits demonstrated in landmark studies like the UK Prospective Diabetes Study (UKPDS). Recent years have witnessed expanded applications, including revised safety guidelines for renal impairment, investigations into potential anti-cancer effects, and exploration of its role in healthy aging. While newer antihyperglycemic agents with demonstrated cardiorenal benefits have emerged, metformin maintains fundamental importance in treatment algorithms, either as monotherapy or in combination regimens. Future perspectives include optimizing personalized therapy approaches, exploring novel formulations, and investigating metformin's potential in metabolic disease prevention. This review synthesizes current evidence supporting metformin's ongoing relevance while addressing contemporary challenges in its positioning within an increasingly complex therapeutic landscape for T2DM management.