Skip to content

Study · Observational study · n = 312 · 2025

5 results

Effectiveness of oral semaglutide versus empagliflozin for the management of type 2 diabetes. PIONEER-2 trial emulation with real-world data.

Fadini GP, Longato E, Poletto S, Giaccari A, Ghiani M, Strazzabosco M, Trombetta M, Penno G, Avogaro A, Solini A, Consoli A

Diabetes, obesity & metabolism24 Sept 2025Cited by 2 (Europe PMC)

PMID40990044 (opens in a new tab)PMCIDPMC12587239 (opens in a new tab)DOI10.1111/dom.70151 (opens in a new tab)PepBankPUB-40990044
Download PDFPubMedAsk about this study
Jump to 5 results

Summary

Background and aimsOral semaglutide and empagliflozin are commonly used for the management of type 2 diabetes (T2D), but head-to-head comparisons in real-world settings are limited. We aimed to emulate the PIONEER-2 trial using electronic health records to compare the effectiveness and persistence of oral semaglutide versus empagliflozin.MethodsThis was a retrospective multicentre study using electronic health records from Italian diabetes clinics. New users of oral semaglutide or empagliflozin were matched 1:2 and followed for up to 18 months. The primary outcome was HbA1c change; secondary outcomes included weight change and treatment persistence. Analyses used mixed models for repeated measures under both treatment policy and trial product estimands.ResultsAfter matching, we included new users of oral semaglutide (n = 105) or empagliflozin (n = 207). Mean age was 65 years, diabetes duration 10 years, baseline HbA1c 7.6%, BMI 29 kg/m2, and 94% were on metformin. Only 28.6% of new users of oral semaglutide reached the 14 mg dose and 31.4% of empagliflozin new users reached the 25 mg dose. HbA1c reduction was significantly greater with oral semaglutide than with empagliflozin (mean difference - 0.35%, p <0.001). Weight loss over time was similar, with oral semaglutide showing a modest advantage at 18 months among persistent patients. Persistence was lower for semaglutide (HR for discontinuation 1.47, p = 0.007).ConclusionsUnder routine care, new users of oral semaglutide achieved better glycaemic control compared with empagliflozin new users, with similar weight loss but lower treatment persistence. These findings support the results of PIONEER-2 and its transferability to clinical practice.
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 adults with type 2 diabetes in routine care, HbA1c fell more with oral semaglutide than with empagliflozin.

    In plain wordsIn adults with type 2 diabetes in routine care, oral semaglutide lowered HbA1c more than empagliflozin did.

    Peptide
    Semaglutide
    Outcome
    DecreaseHbA1c reduction
    Study

    n = 312

    Comparator
    Empagliflozin
    Analysis
    Primary
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated · oral · up to 18 monthsAs given in this study (human).

    Measurements

    HbA1c mean difference
    −0.35%
    oral semaglutide vs empagliflozin

    Source sentences

    Summary
    HbA1c reduction was significantly greater with oral semaglutide than with empagliflozin (mean difference - 0.35%, p <0.001).
    2 context sentences
    Summary · context
    This was a retrospective multicentre study using electronic health records from Italian diabetes clinics.
    Summary · context
    New users of oral semaglutide or empagliflozin were matched 1:2 and followed for up to 18 months.
  2. 02HumanObservational studyEfficacy outcome

    In adults with type 2 diabetes in routine care, weight loss over time was similar with oral semaglutide and empagliflozin.

    In plain wordsIn adults with type 2 diabetes in routine care, weight loss over time was similar with oral semaglutide and empagliflozin.

    Peptide
    Semaglutide
    Outcome
    No significant changeWeight change over time
    Study

    n = 312

    Comparator
    Empagliflozin
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · oral · up to 18 monthsAs given in this study (human).

    Source sentences

    Summary
    Weight loss over time was similar
    2 context sentences
    Summary · context
    This was a retrospective multicentre study using electronic health records from Italian diabetes clinics.
    Summary · context
    New users of oral semaglutide or empagliflozin were matched 1:2 and followed for up to 18 months.
  3. 03HumanObservational studyEfficacy outcome

    In adults with type 2 diabetes in routine care, discontinuation was more likely with oral semaglutide than with empagliflozin.

    In plain wordsIn adults with type 2 diabetes in routine care, people stopped oral semaglutide more often than empagliflozin.

    Peptide
    Semaglutide
    Outcome
    IncreaseTreatment persistence (discontinuation)
    Study

    n = 312

    Comparator
    Empagliflozin
    Analysis
    Secondary
    Outcome group
    Patterns of use · Whole body
    Studied dose
    Dose not stated · oral · up to 18 monthsAs given in this study (human).

    Measurements

    Hazard ratio for discontinuation
    1.47 HR
    oral semaglutide vs empagliflozin

    Source sentences

    Summary
    Persistence was lower for semaglutide (HR for discontinuation 1.47, p = 0.007).
    2 context sentences
    Summary · context
    This was a retrospective multicentre study using electronic health records from Italian diabetes clinics.
    Summary · context
    New users of oral semaglutide or empagliflozin were matched 1:2 and followed for up to 18 months.
  4. 04HumanObservational studyEfficacy outcome

    Among persistent patients with type 2 diabetes, oral semaglutide showed a modest weight-loss advantage over empagliflozin at 18 months.

    In plain wordsAmong people who stayed on treatment, oral semaglutide gave a small extra weight loss compared with empagliflozin at 18 months.

    Peptide
    Semaglutide
    Outcome
    DecreaseWeight change at 18 months among persistent patients
    Study

    n: not reported in source

    Comparator
    Empagliflozin
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · oral · up to 18 monthsAs given in this study (human).

    Source sentences

    Summary
    with oral semaglutide showing a modest advantage at 18 months among persistent patients.
    2 context sentences
    Summary · context
    This was a retrospective multicentre study using electronic health records from Italian diabetes clinics.
    Summary · context
    New users of oral semaglutide or empagliflozin were matched 1:2 and followed for up to 18 months.
  5. 05HumanObservational studyOther

    Only 28.6% of new users of oral semaglutide reached the 14 mg dose.

    In plain wordsIn routine care, fewer than a third of new oral semaglutide users reached the 14 mg dose.

    Peptide
    Semaglutide
    Outcome
    Not applicableProportion reaching the 14 mg dose
    Study

    n = 105

    Outcome group
    Patterns of use · Pharmacology
    Studied dose
    Dose not stated · oral · up to 18 monthsAs given in this study (human).

    Measurements

    Proportion reaching 14 mg
    28.6%
    oral semaglutide new users

    Source sentences

    Summary
    Only 28.6% of new users of oral semaglutide reached the 14 mg dose
    2 context sentences
    Summary · context
    This was a retrospective multicentre study using electronic health records from Italian diabetes clinics.
    Summary · context
    New users of oral semaglutide or empagliflozin were matched 1:2 and followed for up to 18 months.

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.

PepBank is a research reference. Talk to a doctor before you use any peptide.