Oral semaglutide in patients with type 2 diabetes and cardiovascular disease, renal impairment, or other comorbidities, and in older patients
Open accessAbstract
Patients with type 2 diabetes (T2D) often have comorbidities, such as cardiovascular disease or chronic kidney disease, and a large and growing proportion of the T2D patient population is over 65 years. There are many therapies for the treatment of T2D but not all are suitable for patients with comorbidities. Oral semaglutide is a tablet formulation of a glucagon-like peptide-1 receptor agonist (GLP-1RA) and was recently approved for the treatment of T2D, representing an oral alternative to injectable GLP-1RAs. This article reviews data from: PIONEER 6, a phase 3a cardiovascular outcomes trial in patients at high cardiovascular risk; PIONEER 5, a phase 3a trial in patients with moderate renal impairment; a post-hoc analysis of PIONEER data by age; and pharmacokinetic trials investigating the effects of renal impairment, gastrointestinal disease, and hepatic impairment on the exposure of oral semaglutide. PIONEER 6 demonstrated the cardiovascular safety of oral semaglutide compared with placebo (hazard ratio: 0.79; 95% confidence interval [CI]: 0.57, 1.11; p < 0.001 for noninferiority), ruling out excess cardiovascular risk. In PIONEER 5, oral semaglutide was superior to placebo in decreasing glycated hemoglobin over 26 weeks (estimated treatment difference [ETD]: -0.8%; 95% CI: -1.0, -0.6; p < 0.0001) and body weight (ETD: -2.5 kg; 95% CI: -3.2, -1.8; p < 0.0001), and renal function was unchanged in both treatment groups. There was no effect of age on glycemic efficacy of oral semaglutide and the presence of upper gastrointestinal disease or hepatic impairment did not affect the pharmacokinetics of semaglutide. Across the trials, the safety profile of oral semaglutide was as expected for a GLP-1RA, with gastrointestinal adverse events most commonly reported. As such, oral semaglutide provides an effective oral GLP-1RA treatment option in older patients and/or those with comorbidities, with no requirements for dose adjustment.
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An exploratory analysis of oral semaglutide showed a tendency for higher rates of premature trial product discontinuation due to adverse events with increasing age.
“An exploratory analysis of evaluating the effect of patient age on the safety of oral semaglutide showed that there was a tendency for higher rates of premature trial product discontinuation due to AEs with increasing age (28).”
From Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system (2022) · cites this paper as [28]
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References 48 · Cited by 16
- Authors
- Mosenzon, O., Miller, E. M., & Warren, M. L.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Diabetes Nation, Bend, OR, USA
- Physicians East (US)
- Corresponding author
- Mosenzon, Ofri
- Venue
- Postgraduate Medicine
- Publisher
- Informa UK Limited
- Published
- 2020-09-08
- Volume
- 132
- Issue
- sup2
- Pages
- 37-47
- ISSN
- 0032-5481 (ISSN-L)
- 1941-9260
- OpenAlex
- W3081499157
- Cited by
- 16
- References
- 48
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 3
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Postgraduate Medicine (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk Inc
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- oral semaglutide, type 2 diabetes, GLP-1 receptor agonists, cardiovascular outcomes, Pioneer 6, renal dysfunction, chronic kidney disease, elderly patients, pharmacokinetics, liver dysfunction, upper gastrointestinal diseases, glycemic control, weight loss, comorbidities
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide, Age Factors, Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Humans, Hypoglycemic Agents, Kidney Failure, Chronic, Comorbidity, Randomized Controlled Trials as Topic
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