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May 24, 2026International Journal of Molecular SciencesOpen Access

Retrospective Comparative Study of Oral Versus Subcutaneous Semaglutide in Patients with Type 2 Diabetes Mellitus

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Key result

Oral semaglutide matches subcutaneous semaglutide for HbA1c and BMI reduction in type 2 diabetes.

  • n=434

Why the study?

Does oral semaglutide compare effectively to subcutaneous semaglutide in reducing HbA1c and BMI in adult patients with type 2 diabetes mellitus?

Population

434 adult patients with type 2 diabetes mellitus followed at the ASUGI Diabetes Center, median age 70 years…

Comparison

Oral semaglutide vs Subcutaneous (sc) semaglutide

Design

Cohort

Follow-up

18 months

Authors

BTBarbara ToffoliOspedale di CattinaraMMMatteo MichielettoOspedale di CattinaraSBStella BernardiOspedale di Cattinara

Discussion

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Implication

Oral and subcutaneous semaglutide demonstrate comparable real-world effectiveness in reducing HbA1c and BMI in patients with type 2 diabetes.

Key Points

  • This study aims to compare the effectiveness of oral versus subcutaneous semaglutide on metabolic parameters in patients with type 2 diabetes mellitus.
  • Retrospective real-world study including 434 patients with type 2 diabetes taking either oral (n=232) or subcutaneous (n=202) semaglutide.
  • Data analysis involved multivariate linear regression models and propensity score matching to address BMI imbalances.
  • Follow-up at 18 months for both treatment groups.
  • Both oral and subcutaneous semaglutide effectively reduced HbA1c and BMI without significant differences.
  • Oral semaglutide showed a greater reduction in diastolic blood pressure compared to subcutaneous semaglutide.
  • Concomitant therapy with SGLT2 inhibitors enhanced reductions in total and LDL cholesterol.

Study Design

Type

Cohort (n=434)

Multicenter

No

Structured PICO

Does oral semaglutide compare effectively to subcutaneous semaglutide in reducing HbA1c and BMI in adult patients with type 2 diabetes mellitus?

P
Population
434 adult patients with type 2 diabetes mellitus (median age 70 years) treated with oral or subcutaneous semaglutide, with a subset followed for 18 months.
E
Exposure
Oral semaglutide
C
Comparator
Subcutaneous (sc) semaglutide
O
Outcome
Change in HbA1c and BMI at 18-month follow-upsurrogate

Oral and subcutaneous semaglutide demonstrate comparable real-world effectiveness in reducing HbA1c and BMI in patients with type 2 diabetes.

Cite This Study

Toffoli et al. (2026) conducted a cohort in Type 2 diabetes mellitus (n=434). Oral semaglutide vs. Subcutaneous semaglutide was evaluated on Change in HbA1c and BMI. Oral semaglutide was comparably effective to subcutaneous semaglutide in reducing HbA1c and BMI among 434 patients with type 2 diabetes in a real-world setting.

synapsesocial.com/papers/6a1295e248a0ea1665672438https://doi.org/10.3390/ijms27114694
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes2016 · 6,939 citations
  2. 2Real-World Use of Oral and Subcutaneous Semaglutide in Routine Clinical Practice in the UK: A Single-Centre, Retrospective Observational Study2024 · 18 citations
  3. 3Sex specific responses to oral vs. subcutaneous semaglutide in type 2 diabetes mellitus: A 12-month real-world study2025 · 2 citations
  4. 4Oral versus subcutaneous semaglutide weight loss outcomes after two years among patients with type 2 diabetes in a real-world database2025 · 6 citations
  5. 5Efficacy of oral semaglutide: overview of the PIONEER clinical trial program and implications for managed care2020 · 42 citations