Effectiveness of oral semaglutide versus empagliflozin for the management of type 2 diabetes. PIONEER ‐2 trial emulation with real‐world data
Main finding · HbA1c changeResult — go to the resultMean difference - 0.35 %Authors' conclusion
Under 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.
Study context
- Population
- New users of oral semaglutide or empagliflozin with T2D, Italian diabetes clinics; mean age 65 years, diabetes duration 10 years, baseline HbA1c 7.6%, BMI 29 kg/m², 94% on metforminmatched 1:2
- Participants
- 105 vs 207
- Exposure
- Oral semaglutide vs empagliflozin
- Oral semaglutiden = 105
- Empagliflozinn = 207reference
- Outcome
- HbA1c change
- Follow-up
- Up to 18 months
Methodological detailstarget trial emulation of PIONEER-2, multicentre, electronic health records, matched 1:2, mixed models for repeated measures, treatment policy and trial product estimands
- Target trial emulation of PIONEER-2
- Multicentre
- Electronic health records
- Matched 1:2
- Mixed models for repeated measures
- Treatment policy and trial product estimands
Main finding
As reported in the abstract
Mean difference
- 0.35 %
P < 0.001
Observational data: associations, not effects.
Secondary outcomes
Weight change · up to 18 months
- Weight loss over time was similar, with oral semaglutide showing a modest advantage at 18 months among persistent patients
Treatment persistence
- Persistence lower for semaglutide; HR for discontinuation
- 1.47, p = 0.007
Original publication
Effectiveness of oral semaglutide versus empagliflozin for the management of type 2 diabetes. PIONEER ‐2 trial emulation with real‐world data. Diabetes Obes Metab. Published 24 September 2025. doi:10.
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