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. 2025 Jun 8;18(6):856.
doi: 10.3390/ph18060856.

Real-World Analysis of Short-Term Effectiveness of Oral Semaglutide: Impact on Glycometabolic Control and Cardiovascular Risk

Sara Palazzi  1 , Federica Sentinelli  1 , Antonella Zugaro  2 , Sara Morgante  2 , Livia Santarelli  3 , Sandra Melanzi  3 , Annamaria De Mutiis  3 , Deamaria Piersanti  4 , Barbara Macerola  4 , Marco Iezzi  4 , Pietro Mercuri  4 , Alessandro Ferranti  1 , Daniele Tienforti  1 , Maria Gisella Cavallo  5 , Arcangelo Barbonetti  1 , Marco Giorgio Baroni  1   2   6
Affiliations

Real-World Analysis of Short-Term Effectiveness of Oral Semaglutide: Impact on Glycometabolic Control and Cardiovascular Risk

Sara Palazzi et al. Pharmaceuticals (Basel). .

Abstract

Background: Oral semaglutide, a GLP1-receptor agonist (GLP1-RA), shows promise in efficacy and compliance, especially amid the global shortage of injectable GLP-1 RAs. Its short-term effectiveness remains unexplored. Objective: This real-world observational study assessed the short-term effectiveness of oral semaglutide after three months of therapy. Methods: Patients with type 2 diabetes from four Italian diabetes centers, who received an initial prescription of oral semaglutide, were reassessed after three months. Primary outcomes included glycated hemoglobin (HbA1c) and body weight reduction; secondary outcomes involved changes in lipid parameters and cardiovascular risk. Results: Among 167 participants (mean age 66.5 years, mostly obese, baseline HbA1c 8.4% ± 1.5), 83.2% received a 7 mg dose. After three months, HbA1c significantly declined (8.4% to 7.1%, -1.3%, p < 0.001), alongside body mass index (BMI) (30.9 kg/m2 to 29.6 kg/m2, p < 0.0001). The target HbA1c ≤ 7% was achieved by 54.5%, and 34.7% reached ≤6.5%. Patients losing >5% of their initial weight (30.5%) saw the largest HbA1c drop (-1.9%). Those with newly diagnosed diabetes or a duration < 5 years showed superior responses (p = 0.001), while no significant differences were found based on the timing of drug administration. Oral semaglutide replaced or supplemented prior therapies, allowing discontinuation of dipeptidyl peptidase 4 inhibitors (DPP4i), sulfonylureas, glinides, and acarbose, and deprescription of thiazolidinediones. A significant reduction in cardiovascular risk was observed (p = 0.04), together with a significant reduction in lipid parameters. Conclusions: Oral semaglutide showed significant short-term efficacy, reducing HbA1c, body weight, and cardiovascular risk in three months, making it a valuable therapeutic option.

Keywords: BMI; GLP1-receptor agonist; HbA1c; duration of diabetes; type 2 diabetes; weight.

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Conflict of interest statement

The authors declare no conflicts of interest. The funder had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Graphical representation of changes in frequency of use of oral and/or injectable hypoglycemic agents before (T0, grey columns) and after (T1, black columns) introduction of oral semaglutide. Abbreviations: DPP4i: dipeptidyl peptidase 4 inhibitors, SGLT2i: sodium-glucose cotransporter 2 inhibitors, GLP1ra: glucagon-like peptide-1 receptor agonists.
Figure 2
Figure 2
(A) Mean HbA1c values (expressed as percentages) at T0 (white columns) and T1 (grey columns) based on different classes of diabetes duration (* p < 0.001; paired t-test); (B) mean HbA1c values at T1 in subjects with diabetes diagnosis <5 years and >5 years (* p < 0.001; t-test).
Figure 3
Figure 3
Changes in cardiovascular risk classes between T0 and T1. Data are reported as percentages.
See this image and copyright information in PMC

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