Effectiveness of oral semaglutide versus empagliflozin for the management of type 2 diabetes. PIONEER-2 trial emulation with real-world data
Abstract
BACKGROUND AND AIMS: Oral 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.
METHODS: This 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.
RESULTS: After 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).
CONCLUSIONS: Under routine care, new users of oral…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 207 participants or records.
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