Long-term metabolic regulation in the era of GLP-1 receptor agonists: An integrative review of Ayurvedic and biomedical perspectives

Obesity and type 2 diabetes mellitus (T2DM) are chronic, relapsing, and multifactorial disorders arising from long-term dysregulation of metabolic, neuroendocrine, behavioral, and environmental systems. Glucagon-like peptide-1 (GLP-1) receptor agonists represent a major advance in contemporary metabolic pharmacotherapy. Among them, semaglutide has demonstrated robust efficacy in improving glycemic control, inducing clinically meaningful weight loss, and reducing cardiovascular and renal risk in high-risk populations through well-established molecular and physiological mechanisms. Despite these benefits, challenges related to long-term metabolic sustainability persist, including weight regain after discontinuation, loss of lean mass defined as the reduction in skeletal muscle and non-adipose body tissue and the need for prolonged or lifelong therapy. These observations highlight the adaptive nature of human energy homeostasis and underscore the importance of approaches that support durable metabolic regulation beyond appetite suppression alone. This discussion uses semaglutide as a case example to explore how integrative frameworks, particularly Ayurveda, may complement pharmacotherapy by offering systems-level perspectives on digestion, regulation, tissue integrity, and behavioral rhythms. Ayurvedic concepts are employed as interpretive analogues rather than mechanistic explanations, with the aim of contextualizing why short-term metabolic improvements may not always translate into long-term resilience. Rather than positioning traditional knowledge systems in opposition to evidence-based medicine, this paper argues for a complementary model in which pharmacotherapy stabilizes acute metabolic risk while integrative lifestyle-oriented strategies support sustained metabolic health.