Subcutaneous semaglutide, at a 2.4 mg once-weekly maintenance dose, is approved in the United States for weight management in individuals with a body mass index (BMI) of 30 kg/mor higher, or with a BMI of 27 kg/mor higher and at least one obesity-related co-morbidity. To investigate the usability of the semaglutide pen-injector in individuals who met these criteria, we report post hoc analysis of the summative (human factors validation) usability testing and safety analysis involving patients with type 2 diabetes (an obesity-related co-morbidity) with the same pen-injector, limited to the 26 out of 30 patients with a BMI of 27 kg/mor higher (11 pen-injector-naïve, 15 pen-injector-experienced) and 15 non-pharmacist healthcare professionals (HCPs). Participants performed two simulated injections into an injection pad. No potentially serious use errors occurred. Mean subjective ease-of-use rating on a seven-point scale, where 1 = difficult and 7 = easy, was 6.9 for the second injection in all three groups. These results suggest that the semaglutide pen-injector is easy to use and not associated with serious use errors when used by pen-injector-naïve or pen-injector-experienced patients meeting the requirement for weight management with semaglutide treatment, and by non-pharmacist HCPs.