Liraglutide-Metformin Combination Therapy in Type 2 Diabetes: A Comprehensive Review of Clinical Efficacy, Safety and Cost-Effectiveness

Type 2 diabetes (T2D) presents a growing global health challenge, with escalating clinical and economic burdens driven largely by progressive disease and costly complications. This comprehensive review evaluates liraglutide combined with metformin as a second-line treatment option, contrasting its clinical benefits, safety profile, patient-centered outcomes, and economic value against established therapies, including sulfonylureas, DPP-4 inhibitors, and standard care. Evidence from randomized controlled trials, meta-analyses, and landmark cardiovascular outcome studies (e.g., LEAD, LEADER) demonstrates that liraglutide achieves durable glycemic control comparable or superior to sulfonylureas and DPP-4 inhibitors, while offering significant weight reduction and a markedly lower risk of hypoglycemia. Notably, liraglutide confers cardioprotective effects characterized by reductions in major adverse cardiovascular events and mortality. Despite a higher acquisition cost, economic models validate its cost-effectiveness within widely accepted thresholds, primarily through avoidance of diabetes-related complications and hospitalizations. Patient-reported satisfaction correlates positively with clinical efficacy, although real-world adherence varies due to multifactorial influences. While newer agents such as semaglutide show promise for even greater benefits, liraglutide remains a valuable, evidence-based option in contemporary T2D management strategies. Comprehensive individualization of treatment and supportive care are critical to optimizing outcomes and healthcare value.