Patients were 3.2 times more likely to follow all administration instructions correctly with weekly injectable dulaglutide (96.8% compliance) than with daily oral semaglutide (90.4%) in Spanish clinical practice.
3.2x higher odds of full compliancePatients on weekly injectable dulaglutide were 3.2 times more likely to follow all administration instructions correctly compared to those on daily oral semaglutide.
What the researchers found
Among 95 dulaglutide users and 135 oral semaglutide users, compliance with all package leaflet administration instructions was 96.8% for weekly injectable dulaglutide versus 90.4% for daily oral semaglutide. After adjusting for potential between-group imbalances, the odds ratio for higher compliance with dulaglutide was 3.2 (95% CI: 1.4-21.3), indicating significantly better adherence to administration instructions.
The lower compliance with oral semaglutide is attributed to its complex administration requirements: taking it first thing in the morning on an empty stomach with no more than 120 mL of plain water, then waiting at least 30 minutes before eating, drinking, or taking other medications.
Why it matters
Medication compliance directly affects treatment outcomes. If patients don't take oral semaglutide correctly (especially the fasting and waiting requirements), absorption is reduced and the drug may not work as well. This real-world data helps clinicians choose between GLP-1 drug formulations based on which their patients are more likely to use correctly — not just which is theoretically more convenient.
How the study worked
Observational cross-sectional study conducted in Endocrinology Units across Spain. Patients with T2D who had been on weekly dulaglutide or daily oral semaglutide for 3-12 months were consecutively recruited during routine visits. Clinical data were extracted from medical records. An ad-hoc questionnaire assessed how often patients followed each administration instruction. Compliance was compared between groups using logistic regression with adjustment for sociodemographic and clinical imbalances.
What this study cannot tell us
The wide confidence interval (1.4-21.3) suggests imprecision, likely due to the small sample size. The study was observational and cross-sectional, not randomized, so inherent differences between patients who were prescribed each drug may influence results. Self-reported compliance may overestimate actual adherence. The study was conducted in Spanish Endocrinology Units and may not generalize to primary care or other countries. The study was supported by Eli Lilly (manufacturer of dulaglutide), which is a potential conflict of interest.
How to read the evidence
This is a real-world observational cross-sectional study with self-reported compliance data. The sample size is modest (230 patients) and the wide confidence interval limits precision. The industry sponsorship by Eli Lilly (dulaglutide manufacturer) should be noted when interpreting results.
When this study was published
Published in 2025, this is current and addresses an active clinical question as oral GLP-1 formulations become more widely prescribed.
The bigger picture
The availability of oral semaglutide was expected to improve adherence by eliminating injections. This study suggests the opposite may be true — the complex oral administration requirements create compliance challenges that offset the convenience of avoiding needles. This is important as the GLP-1 market expands with more oral formulations in development. The finding aligns with broader adherence research showing that simpler, less-frequent dosing regimens generally produce better compliance.
Questions still open
- Does the compliance difference between these formulations translate into measurable differences in glycemic control in real-world practice?
- Would newer oral GLP-1 formulations with simplified administration requirements achieve higher compliance rates?
- How does patient preference and satisfaction compare between the two formulations independent of compliance outcomes?
Common questions
Why is taking oral semaglutide more complicated than an injection?
Does this mean injections are better than pills for GLP-1 drugs?
Read the original research
Higher Compliance with Treatment Administration Instructions for Injectable Dulaglutide versus Oral Semaglutide Reported by People with Type 2 Diabetes in Clinical Practice Settings in Spain: The TRU-Experience Study.
Patient preference and adherence, 19, 1231-1244
Citation
Díaz-Cerezo, Silvia; Artime, Esther; Redondo-Antón, Jennifer; Duque, Natalia; Spaepen, Erik; Mangas Cruz, Miguel Ángel; Arnas-Leon, Claudia; Olveira, Gabriel; Rodríguez, Irene Rodríguez; Julián Alagarda, María Teresa; Valdés, Nuria; Merchante, Agustín Ángel; Masmiquel, Lluís; Rubio-de Santos, Miriam. (2025). Higher Compliance with Treatment Administration Instructions for Injectable Dulaglutide versus Oral Semaglutide Reported by People with Type 2 Diabetes in Clinical Practice Settings in Spain: The TRU-Experience Study.. Patient preference and adherence, 19, 1231-1244. https://doi.org/10.2147/PPA.S509483