Imaging in Semaglutide Study

Type 2 diabetes (T2D),characterized by insulin resistance and abnormal metabolic functions, is the most prevalent metabolic syndrome disease (1). Excess weight gain is the number one risk factor for development of T2D, in which 85% of individuals with T2D are either overweight or obese (2). While weight management through diet and exercise is foundational for treatment, genetic and environmental factors pose challenges (3). Recently, once-weekly subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), and tirzepatide, a gastric inhibitory peptide/glucagon-like peptide-1 dual receptor agonist (GIP/GLP-1RA), were approved for the treatment of T2D as well as obesity (4, 5). They have displayed significant efficacy in improving glycemic control and weight reduction in both individuals with overweight or obesity with or without T2D (6). However, the significant weight loss associated with these medications is not only related to reduction in body fat mass, but also loss of body lean mass, as observed in previous clinical studies (7). Indeed, this raises concern in older individuals for the development of sarcopenic obesity, a medical condition defined by the presence of both sarcopenia (loss of muscle) and obesity, a condition associated with poor morbidity and mortality (7, 8). However, it remains unclear whether the substantial reduction in body fat and lean mass is directly associated with changes in skeletal muscle volume, strength, quality and metabolic function. This proposal aims to address this gap by evaluating the longitudinal effect of semaglutide treatment on skeletal muscle metabolic function in individuals with T2D and obesity. The study will evaluate skeletal muscle strength of the patients of T2D and obesity undergoing semaglutide therapy and leverage MRI and phosphorus-31 magnetic resonance spectroscopy (31P-MRS) to assess changes in skeletal muscle volume, quality and metabolic functions pertaining to muscle mitochondria.