Efficacy and Safety in a Real-World Study of the New Oral Formulation of Semaglutide in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus

<b>Background/Objectives:</b> GLP-1 receptor agonists (GLP-1RAs) have emerged as fundamental components in the treatment of type 2 diabetic patients (T2DM) with chronic kidney disease (CKD). The oral formulation represents a novel therapeutic tool but may affect drug efficacy. This study sought to compare the effectiveness of subcutaneous versus oral semaglutide formulations in patients with CKD. <b>Methods:</b> A retrospective study in a real-world setting compared type 2 diabetes and chronic kidney disease patients, initiating oral semaglutide treatment to a historically matched control group treated with subcutaneous semaglutide. The matching considered factors such as estimated glomerular filtration rate (eGFR), age, and sex. <b>Results:</b> Nineteen patients were included in both groups, with a mean age of 68.0. Seventy-two percent were males with a CKD-EPI eGFR of 49.9 mL/min/1.73 m² and a median urine albumin-to-creatinine ratio of 12.7 mg/g. Of the study participants, 94% and 79% of patients were on the maximum semaglutide sbc vs. oral dose, while 5.3% and 15.8% were on the sbc vs. oral low dose. Oral semaglutide significantly reduced HbA1C and BMI, identical to the control group (-0.9 and -1.4, <i>p</i> > 0.05). Renal function parameters and blood pressure remained stable throughout the follow-up in both groups. The main side effect was digestive intolerance (affecting three patients in the oral group and two patients in the subcutaneous group, <i>p</i> = 0.6), although the treatment abandonment percentage was similar. <b>Conclusions:</b> The oral formulation of semaglutide demonstrated equivalent effectiveness in glucose control and body weight management in patients with T2DM and CKD, even with a higher proportion of patients receiving low to medium doses. Gastrointestinal side effects were comparable between both oral and subcutaneous formulations.