Safety and tolerability of semaglutide across the SUSTAIN and PIONEER phase IIIa clinical trial programmes
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Glucagon-like peptide-1 receptor agonists improve glycaemic control: some are now available as oral and subcutaneous formulations, and some have indications for reducing cardiovascular risk. The expanded scope for these therapies warrants comprehensive safety evaluations. We report the safety/tolerability of subcutaneous and oral semaglutide from the SUSTAIN and PIONEER clinical trial programmes, respectively.
Materials and methods
Adverse events (AEs) from 16 randomized placebo- or active-controlled phase IIIa trials in patients with type 2 diabetes (n = 11 159) including once-weekly subcutaneous semaglutide (n = 3150; SUSTAIN trials) or once-daily oral semaglutide (n = 4116; PIONEER trials) were analysed. Data pools were analysed for each programme, with separate analyses of cardiovascular outcomes trials (CVOTs; n = 6480).
Results
In the phase IIIa pools, gastrointestinal disorders were reported in 41.9%/39.1% of patients with subcutaneous/oral semaglutide, respectively (most prevalent during initiation/escalation) versus 22.0%/24.8% with comparators. Rates of kidney disorders, acute pancreatitis, malignant neoplasms, hypoglycaemia, diabetic retinopathy, heart failure and other cardiovascular events were similar for semaglutide versus comparators. Cholelithiasis incidence was higher with subcutaneous and oral semaglutide versus placebo. Diabetic retinopathy incidence was higher with subcutaneous semaglutide versus placebo in SUSTAIN 6. Small pulse rate increases occurred with both formulations; there was no increased rate of arrhythmias. Fatal AE incidence was similar between semaglutide and comparators. Versus placebo, CVOTs showed a reduced risk of major adverse cardiovascular events with subcutaneous semaglutide and non-inferiority criteria were met with oral semaglutide.
Conclusions
The most common AEs with semaglutide were gastrointestinal disorders, which decreased with continued therapy. These comprehensive safety/tolerability data may better inform patient selection and guidance in care.
Originalsprog | Engelsk |
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Tidsskrift | Diabetes, Obesity and Metabolism |
Vol/bind | 25 |
Udgave nummer | 5 |
Sider (fra-til) | 1385-1397 |
Antal sider | 13 |
ISSN | 1462-8902 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
The authors would like to recognize the extensive collaborative effort required to understand the comprehensive safety profile of any new therapeutic agent and thus extend appreciation to all trial participants, investigators and trial site staff, data monitoring committees and sponsor (Novo Nordisk) employees involved in these trials. The authors would like to thank Banafsheh Zahedi and Srikanth Deenadayalan for critically reviewing the manuscript. The authors would also like to thank Rebecca Bridgewater‐Gill, PhD, of Axis, a division of Spirit Medical Communications Group Limited, for assistance with medical writing and editorial support (funded by Novo Nordisk A/S).
Publisher Copyright:
© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
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