Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: Rationale, design and patient baseline characteristics for the PIONEER 6 trial

Aims To assess the cardiovascular (CV) safety of oral semaglutide, the first tablet formulation of a glucagon‐like peptide‐1 receptor agonist. Materials and methods PIONEER 6 is a multinational, randomized, placebo‐controlled, double‐blind trial in patients with type 2 diabetes at high risk of CV ev...

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Published in:Diabetes, obesity & metabolism obesity & metabolism, 2019-03, Vol.21 (3), p.499-508
Main Authors: Bain, Stephen C., Mosenzon, Ofri, Arechavaleta, Rosario, Bogdański, Pawel, Comlekci, Abdurrahman, Consoli, Agostino, Deerochanawong, Chaicharn, Dungan, Kathleen, Faingold, Maria C., Farkouh, Michael E., Franco, Denise R., Gram, Jeppe, Guja, Cristian, Joshi, Pankaj, Malek, Rachid, Merino‐Torres, Juan F., Nauck, Michael A., Pedersen, Sue D., Sheu, Wayne H. ‐H., Silver, Robert J., Tack, Cees J., Tandon, Nikhil, Jeppesen, Ole K., Strange, Mette, Thomsen, Mette, Husain, Mansoor
Format: Article
Language:English
Subjects:
Administration, Oral
Aged
Aged, 80 and over
Antidiabetics
cardiovascular disease
Cardiovascular Diseases - epidemiology
Cardiovascular Diseases - prevention & control
cardiovascular outcomes trial
Cardiovascular System - drug effects
Cerebral infarction
Clinical Trial Design
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - epidemiology
Diabetic Angiopathies - epidemiology
Diabetic Angiopathies - prevention & control
Double-Blind Method
Female
GLP‐1 receptor agonist
Glucagon
Glucagon-Like Peptides - administration & dosage
Glucagon-Like Peptides - adverse effects
Hemoglobin
Humans
Hypoglycemic Agents - administration & dosage
Hypoglycemic Agents - adverse effects
Kidney diseases
Male
Metformin - administration & dosage
Metformin - adverse effects
Middle Aged
Myocardial infarction
oral semaglutide
Placebos
Renal Insufficiency, Chronic - complications
Renal Insufficiency, Chronic - drug therapy
Renal Insufficiency, Chronic - epidemiology
Safety
type 2 diabetes
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Summary:Aims To assess the cardiovascular (CV) safety of oral semaglutide, the first tablet formulation of a glucagon‐like peptide‐1 receptor agonist. Materials and methods PIONEER 6 is a multinational, randomized, placebo‐controlled, double‐blind trial in patients with type 2 diabetes at high risk of CV events (defined as being aged ≥50 years and having established CV disease [CVD] or moderate [stage 3] chronic kidney disease [CKD], or being aged ≥60 years with ≥1 other CV risk factor). Patients were randomized to once‐daily oral semaglutide (up to 14 mg) or placebo added to standard of care. The primary composite endpoint is time to first occurrence of CV death or non‐fatal myocardial infarction or non‐fatal stroke. The primary hypothesis was to exclude an excess in CV risk with oral semaglutide by assessing non‐inferiority versus placebo for the primary endpoint (non‐inferiority margin of 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio). PIONEER 6 is event‐driven, with follow‐up continuing until accrual of at least 122 primary outcome events. There is no pre‐defined minimal duration. Results Overall, 3183 patients have been enrolled (mean age 66.1 years, 31.6% females) in 214 sites across 21 countries. At baseline, the mean duration of diabetes was 14.9 years, mean glycated haemoglobin concentration was 66 mmol/mol (8.2%), and 84.6% of patients had established CVD/moderate CKD. Conclusions PIONEER 6 will provide evidence regarding the CV safety of oral semaglutide in patients with type 2 diabetes and high CV risk.
ISSN:1462-8902
1463-1326
DOI:10.1111/dom.13553