Background: The number of people with type 2 diabetes is increasing daily, and therefore, effective therapy is needed to successfully regulate glycemia and reduce the risk of associated complications. Recently, an oral formulation of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide has become available. Therefore, the aim of our study was to compare the effectiveness of the new oral formulation and the existing injectable formulation of semaglutide in terms of glycemic and body weight control in a real-world setting. Patients and methods: This was a single-center retrospective observational study conducted at the Rijeka Clinical Hospital Centre. A total of 106 patients with inadequately controlled type 2 diabetes (HbA1c ≥ 7%) on different oral or basal insulin supported oral therapy were enrolled in the study, and data from electronic medical records were retrospectively collected and analyzed from May 2021 to November 2022. All subjects were GLP-1 RA-naive and consequently prescribed 0.5 or 1.0 mg of once weekly injectable semaglutide (IS) or 7 mg or 14 mg of once daily oral semaglutide (OS) for at least 6 months. Glycated hemoglobin (HbA1c), body weight, and body mass index (BMI) were assessed prior to semaglutide administration and after a 6-month follow-up period. The primary endpoint was the change from baseline in HbA1c, and secondary endpoints were the change in body weight and the proportion of participants with a reduction in body weight of ≥5% and ≥10%, respectively, 6 months after the initiation of semaglutide treatment. Results: At the 6-month follow-up, no significant difference was observed between the two formulations in terms of HbA1c reduction (IS −1.1% vs. OS −1.4%, p = 0.126) and weight loss (IS −6.50 kg vs. OS −5.90 kg, p = 0.714). Exactly the same proportion of participants in both groups achieved a weight loss of ≥5% (56.7%, n = 30). A weight loss ≥ 10% was observed in 20.7% (n = 11) of participants administered IS and 15.1% (n = 8) of participants administered OS, respectively (p = 0.454). Conclusion: In a real-world setting, oral semaglutide as an add-on therapy to ongoing antihyperglycemic treatment in patients with inadequately controlled type 2 diabetes who had not previously received GLP-1 RA demonstrated a similar effectiveness as injectable semaglutide in terms of glycemic control and weight loss after 6 months of treatment.