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It binds to ActRIIB with approximately 200-fold greater affinity than to ActRIIA and has been shown to induce skeletal muscle hypertrophy by 7% while preserving muscle function when administered in vivo .[77,78] This antibody was initially tested in muscle-related disorders such as inclusion body myositis [79] and sarcopenia.[78] Then, in 2017, its metabolic effects were explored by Novartis, demonstrating a 20.5% reduction in fat mass and a 3.6% increase in lean mass after 48 weeks of monthly administration with lifestyle intervention in obese patients with type 2 diabetes (NCT03005288).[80] This is currently being followed by an ongoing clinical trial sponsored by Eli Lilly and Company (NCT05616013), in which both bimagrumab and semaglutide are being tested in obese adults to evaluate their combined effects with GLP-1 agonists

GLP-1 receptors in the hypothalamus and brainstem modulate hunger and satiety signaling

Tirzepatide dosing protocols typically start at low levels and increase gradually over months

Tirzepatide had been removed from the shortage list earlier, with wind-downs in early 2025