Oral Semaglutide Induces Loss of Body Fat Mass Without Affecting Muscle Mass in Patients With Type 2 Diabetes

<bold>Background: </bold>Excessive body fat may be a major cause of insulin resistance and diabetes. But body weight reduction by energy restriction may simultaneously reduce both fat and muscle. Skeletal muscle is an important organ for glucose metabolism regulation, and loss of muscle may deteriorate glucose metabolism. Therefore, it is preferable to predominantly reduce fat without significant loss of muscle with weight loss in patients with type 2 diabetes. Previously, the anti-diabetic agent glucagon-like peptide-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide given by injection were reported to decrease fat with less effect on muscle in diabetic patients. Recently oral semaglutide was developed and was reported to decrease body weight, but the effect on muscle has not been fully evaluated.<bold>Methods: </bold>This was a non-interventional retrospective longitudinal study. We evaluated the effect of 24-week treatment with oral semaglutide on body fat and muscle mass in 25 Japanese patients with type 2 diabetes. Laboratory examination and body composition test by bioelectrical impedance analysis (BIA) were performed at baseline, 12 weeks, and 24 weeks, and the effects on glycemic control and body composition were assessed.<bold>Results: </bold>Hemoglobin A1c significantly decreased at 12 weeks and further ameliorated at 24 weeks (8.7 +/- 0.87% at baseline; 7.6 +/- 1.00% at 12 weeks; 7.0 +/- 0.80% at 24 weeks; mean +/- standard error (SE)). While body fat significantly decreased (28.3 +/- 1.52 kg at baseline; 26.8 +/- 1.59 kg at 12 weeks; 25.5 +/- 1.57 kg at 24 weeks; mean +/- SE), whole-body lean mass was not significantly changed (48.1 +/- 1.92 kg at baseline; 47.7 +/- 1.93 kg at 12 weeks; 47.6 +/- 1.89 kg at 24 weeks; mean +/- SE). Furthermore, the appendicular skeletal muscle index (SMI) defined as appendicular skeletal muscle mass (ASM)/height squared (units; kg/m(2)) was also unchanged.<bold>Conclusion: </bold>The 24-week treatment with oral semaglutide ameliorated glycemic control with reduction of body fat but not muscle mass in Japanese patients with type 2 diabetes.