Mounjaro® Re-define treatment expectations on chronic weight management

Abstract

Obesity is a chronic, progressive disease driven by adipocyte dysfunction and ectopic fat accumulation. Diet-induced weight loss triggers powerful compensatory biological mechanisms that favor weight regain. At the cellular level, the progression of obesity is dictated by adipocyte dysfunction. As adipocytes increase in size and number, they trigger local inflammation through the infiltration of inflammatory cells (e.g., macrophages) and the secretion of pro-inflammatory cytokines, specifically Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Monocyte Chemoattractant Protein-1 (MCP-1). This inflammatory cascade is a primary driver of systemic insulin resistance. When the storage capacity of subcutaneous fat is exceeded, "lipid overflow" occurs, resulting in the deposition of ectopic fat in vital metabolic sites, including the liver, pancreas, epicardial, and intermuscular regions. Tirzepatide 15 mg achieved an average body weight reduction of 22.5% at 72 weeks, which was sustained at 22.9% through 176 weeks. In the head-to-head SURMOUNT-5 trial, tirzepatide maximum tolerated dose (MTD) demonstrated superior weight loss compared to semaglutide MTD (-21.6% vs. -15.4% at week 72; p<0.001). Systolic and diastolic blood pressure decreased by 10.2 mmHg and 4.6 mmHg with tirzepatide versus 7.7 mmHg and 3.2 mmHg with semaglutide. In SURMOUNT-MAINTAIN, continuing tirzepatide MTD achieved 100% maintenance of initial weight loss at week 112, compared to significant weight regain upon discontinuation (+14.8% from week 36 to 88). Gastrointestinal events (nausea, diarrhea) were mostly mild-to-moderate and occurred primarily during dose escalation. Once-weekly tirzepatide provides robust, sustained weight reduction, superior efficacy over semaglutide, and clinically meaningful cardiometabolic improvements. Continued treatment is essential to maintain therapeutic benefits and counteract compensatory physiology.

[J Assoc Clin Endocrinol Diabetol Bangladesh, 2026;5(Suppl 1): S29]