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Background/Objectives: 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. Methods: 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. Results: 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 m 2 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, p > 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, p = 0.6), although the treatment abandonment percentage was similar. Conclusions: 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.

(1) Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) increase uric acid excretion. The intensity of uricosuria is linked to glycosuria. (2) Methods: We aim to analyze the effect of SGLT2 inhibitors on urinary fractional excretion (FE) of uric acid and glucose in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in a single-center retrospective study with patients with T2DM and CKD who started on treatment with SGLT2is. Patients on renal replacement therapy or with glucagon-like peptide-1 (GLP1) analogs were excluded. Subgroup analysis was performed according to the estimated glomerular filtration rate (eGFR), the SGLT2i molecule, the main comorbidities, and concomitant treatment. As a secondary objective, the study analyzed the effect of SGLT2 inhibitors on uricemia levels. (3) Results: Seventy-three patients were analyzed, with a mean follow-up of 1.2 years. Uric acid and glucose FE significantly increased after the initiation of SGLT2is. This increase remained stable during the follow-up without differences among eGFR groups. No significant reduction in uricemia was observed. However, a trend towards a decrease was observed. (4) Conclusion: The use of SGLT2is in patients with CKD and T2DM is associated with an increase in uric acid FE, which maintains stability irrespective of glomerular filtration loss at least during 24 months of follow-up.