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Study · Observational study · 2026

5 results

Sex specific responses to oral vs. subcutaneous semaglutide in type 2 diabetes mellitus: A 12-month real-world study.

Piccione A, Bonsangue M, Barone M, Vigneri E, Mineo MI, Tomasello L, Maniscalco L, Pantò F, Arnaldi G, Guarnotta V

Nutrition, metabolism, and cardiovascular diseases : NMCD15 Nov 2025

PMID41475990 (opens in a new tab)DOI10.1016/j.numecd.2025.104462 (opens in a new tab)PepBankPUB-41475990
Publisher pagePubMedAsk about this study
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Summary

Background and aimSemaglutide therapy improves glycaemic control, weight loss, and cardiovascular risk reduction in patients with type 2 diabetes mellitus (T2D). Sex-specific differences in the response to oral versus subcutaneous formulation remain unexplored in real-world settings. This interventional pilot study compares the 12-month effectiveness of oral and subcutaneous semaglutide in a real-world cohort of T2D patients, with focus to sex-based differences in treatment outcomes.Methods and resultsTwo-hundred and twelve T2D patients, equally assigned to oral or subcutaneous semaglutide (n = 106 per group), were enrolled. The primary endpoint was the change in HbA1c. Secondary endpoints included variations in anthropometric and metabolic parameters, analysed both in the overall cohort and through a sex-stratified approach. Two-hundred and eight patients completed the study. In men, subcutaneous semaglutide resulted in significant reductions in delta(Δ)_weight (p = 0.010), Δ_HbA1c (p = 0.037), and Δ_LDL (p = 0.038) compared to the oral formulation. In women, subcutaneous semaglutide led to significantly lower Δ_hepatic steatosis index (p = 0.024). Additionally, women treated with subcutaneous semaglutide showed a significantly greater reduction in Δ_GOT (p = 0.035) compared to men.ConclusionsThis real-world study suggests that subcutaneous semaglutide provides greater metabolic benefits than the oral formulation, particularly in men. Women treated with subcutaneous semaglutide experience more favorable liver responses, emphasizing the personalization of T2D treatment.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

5 results from studies that gave the peptide. 5 results from people.

  1. 01HumanObservational studyEfficacy outcome

    In men with type 2 diabetes, subcutaneous semaglutide reduced HbA1c more than oral semaglutide over 12 months (p = 0.037).

    In plain wordsIn men with type 2 diabetes, injected semaglutide lowered HbA1c more than the oral form over 12 months.

    Peptide
    Semaglutide
    Outcome
    DecreaseHbA1c change in men, subcutaneous versus oral
    Study

    n: not reported in source

    Comparator
    Oral semaglutide
    Analysis
    Primary
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated · subcutaneous · 12 monthsAs given in this study (human).

    Source sentences

    Summary
    In men, subcutaneous semaglutide resulted in significant reductions in delta(Δ)_weight (p = 0.010), Δ_HbA1c (p = 0.037), and Δ_LDL (p = 0.038) compared to the oral formulation.
    2 context sentences
    Summary · context
    The primary endpoint was the change in HbA1c.
    Summary · context
    Two-hundred and twelve T2D patients, equally assigned to oral or subcutaneous semaglutide (n = 106 per group), were enrolled.
  2. 02HumanObservational studyEfficacy outcome

    In men with type 2 diabetes, subcutaneous semaglutide reduced weight more than oral semaglutide over 12 months (p = 0.010).

    In plain wordsIn men with type 2 diabetes, injected semaglutide led to more weight loss than the oral form over 12 months.

    Peptide
    Semaglutide
    Outcome
    DecreaseWeight change in men, subcutaneous versus oral
    Study

    n: not reported in source

    Comparator
    Oral semaglutide
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · subcutaneous · 12 monthsAs given in this study (human).

    Source sentences

    Summary
    In men, subcutaneous semaglutide resulted in significant reductions in delta(Δ)_weight (p = 0.010), Δ_HbA1c (p = 0.037), and Δ_LDL (p = 0.038) compared to the oral formulation.
    1 context sentence
    Summary · context
    Two-hundred and twelve T2D patients, equally assigned to oral or subcutaneous semaglutide (n = 106 per group), were enrolled.
  3. 03HumanObservational studyEfficacy outcome

    In men with type 2 diabetes, subcutaneous semaglutide reduced LDL cholesterol more than oral semaglutide over 12 months (p = 0.038).

    In plain wordsIn men with type 2 diabetes, injected semaglutide lowered LDL cholesterol more than the oral form over 12 months.

    Peptide
    Semaglutide
    Outcome
    DecreaseLDL cholesterol change in men, subcutaneous versus oral
    Study

    n: not reported in source

    Comparator
    Oral semaglutide
    Analysis
    Secondary
    Outcome group
    Lipids · Metabolic and weight
    Studied dose
    Dose not stated · subcutaneous · 12 monthsAs given in this study (human).

    Source sentences

    Summary
    In men, subcutaneous semaglutide resulted in significant reductions in delta(Δ)_weight (p = 0.010), Δ_HbA1c (p = 0.037), and Δ_LDL (p = 0.038) compared to the oral formulation.
    2 context sentences
    Summary · context
    Secondary endpoints included variations in anthropometric and metabolic parameters, analysed both in the overall cohort and through a sex-stratified approach.
    Summary · context
    Two-hundred and twelve T2D patients, equally assigned to oral or subcutaneous semaglutide (n = 106 per group), were enrolled.
  4. 04HumanObservational studyEfficacy outcome

    In women with type 2 diabetes, subcutaneous semaglutide lowered the hepatic steatosis index more than oral semaglutide (p = 0.024).

    In plain wordsIn women with type 2 diabetes, injected semaglutide lowered a fatty liver score more than the oral form.

    Peptide
    Semaglutide
    Outcome
    DecreaseHepatic steatosis index change in women, subcutaneous versus oral
    Study

    n: not reported in source

    Comparator
    Oral semaglutide
    Analysis
    Secondary
    Outcome group
    Liver fat and liver function · Liver
    Studied dose
    Dose not stated · subcutaneous · 12 monthsAs given in this study (human).

    Source sentences

    Summary
    In women, subcutaneous semaglutide led to significantly lower Δ_hepatic steatosis index (p = 0.024).
    2 context sentences
    Summary · context
    Secondary endpoints included variations in anthropometric and metabolic parameters, analysed both in the overall cohort and through a sex-stratified approach.
    Summary · context
    Two-hundred and twelve T2D patients, equally assigned to oral or subcutaneous semaglutide (n = 106 per group), were enrolled.
  5. 05HumanObservational studyEfficacy outcome

    In patients with type 2 diabetes, women on subcutaneous semaglutide had a greater GOT reduction than men on the same treatment (p = 0.035).

    In plain wordsIn people with type 2 diabetes on injected semaglutide, women had a larger fall in a liver enzyme than men.

    Peptide
    Semaglutide
    Outcome
    DecreaseGOT change, women versus men on subcutaneous semaglutide
    Study

    n: not reported in source

    Comparator
    Men treated with subcutaneous semaglutide
    Analysis
    Secondary
    Outcome group
    Liver fat and liver function · Liver
    Studied dose
    Dose not stated · subcutaneous · 12 monthsAs given in this study (human).

    Source sentences

    Summary
    Additionally, women treated with subcutaneous semaglutide showed a significantly greater reduction in Δ_GOT (p = 0.035) compared to men.
    2 context sentences
    Summary · context
    Secondary endpoints included variations in anthropometric and metabolic parameters, analysed both in the overall cohort and through a sex-stratified approach.
    Summary · context
    Two-hundred and twelve T2D patients, equally assigned to oral or subcutaneous semaglutide (n = 106 per group), were enrolled.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    11 Oct 2026, 00:04 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:06 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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