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Oral Semaglutide Reduces HbA(1c) and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses

INTRODUCTION: The efficacy and safety of oral semaglutide, the first oral glucagon-like peptide-1 receptor agonist, were investigated in patients with type 2 diabetes (T2D) in the Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) programme. The current post-hoc exploratory subgroup analyses...

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Autores principales: Pratley, Richard E., Crowley, Matthew J., Gislum, Mette, Hertz, Christin L., Jensen, Thomas B., Khunti, Kamlesh, Mosenzon, Ofri, Buse, John B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994454/
https://www.ncbi.nlm.nih.gov/pubmed/33660198
http://dx.doi.org/10.1007/s13300-020-00994-9
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author Pratley, Richard E.
Crowley, Matthew J.
Gislum, Mette
Hertz, Christin L.
Jensen, Thomas B.
Khunti, Kamlesh
Mosenzon, Ofri
Buse, John B.
author_facet Pratley, Richard E.
Crowley, Matthew J.
Gislum, Mette
Hertz, Christin L.
Jensen, Thomas B.
Khunti, Kamlesh
Mosenzon, Ofri
Buse, John B.
author_sort Pratley, Richard E.
collection PubMed
description INTRODUCTION: The efficacy and safety of oral semaglutide, the first oral glucagon-like peptide-1 receptor agonist, were investigated in patients with type 2 diabetes (T2D) in the Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) programme. The current post-hoc exploratory subgroup analyses evaluated outcomes by background medication and insulin regimen subgroups. METHODS: Data from patients in the PIONEER 3–5, 7 and 8 trials receiving once-daily oral semaglutide (14 mg/flexibly dosed) or a comparator (placebo, sitagliptin 100 mg or liraglutide 1.8 mg) were analysed for efficacy (glycated haemoglobin [HbA(1c)] and body weight changes from baseline to planned end of treatment) and safety outcomes. Patients were grouped according to background medication (metformin, sulphonylurea, thiazolidinedione, sodium-glucose cotransporter-2 inhibitor, insulin, or combinations thereof). Efficacy outcomes were analysed using the trial product estimand (which assumes that patients remained on the trial product without rescue medication use). A separate analysis by background insulin regimen (basal, premixed or basal-bolus) was done for PIONEER 8 using the treatment policy estimand (regardless of trial product discontinuation or rescue medication use). Safety outcomes were analysed descriptively for all patients. RESULTS: In total, 2836 patients receiving oral semaglutide 14 mg/flexibly dosed or comparators were included. Baseline characteristics were generally similar across background medication subgroups within each trial. Diabetes duration tended to be longer in patients receiving more background medications. Greater HbA(1c) and body weight reductions were seen across background medication subgroups with oral semaglutide (changes from baseline: − 1.0 to − 1.5% and − 2.2 to − 5.0 kg, respectively) than with comparators (except for similar HbA(1c) reductions vs liraglutide). There were no statistically significant interactions by treatment and background medication subgroup for change in HbA(1c) or body weight except for change in HbA(1c) (background insulin vs insulin plus metformin) in PIONEER 8 (p = 0.0408). Changes in HbA(1c) and body weight were generally similar across insulin regimen subgroups, without significant treatment interactions by subgroup, and the total daily insulin dose was decreased for patients receiving oral semaglutide. The incidence of adverse events was generally similar in background medication subgroups. CONCLUSION: Oral semaglutide was effective at lowering HbA(1c) and body weight, regardless of background medications, and appears suitable for a broad range of patients with T2D in combination with other glucose-lowering agents. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02607865 (PIONEER 3), NCT02863419 (PIONEER 4), NCT02827708 (PIONEER 5), NCT02849080 (PIONEER 7) and NCT03021187 (PIONEER 8). GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13300-020-00994-9.
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spelling pubmed-79944542021-04-16 Oral Semaglutide Reduces HbA(1c) and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses Pratley, Richard E. Crowley, Matthew J. Gislum, Mette Hertz, Christin L. Jensen, Thomas B. Khunti, Kamlesh Mosenzon, Ofri Buse, John B. Diabetes Ther Original Research INTRODUCTION: The efficacy and safety of oral semaglutide, the first oral glucagon-like peptide-1 receptor agonist, were investigated in patients with type 2 diabetes (T2D) in the Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) programme. The current post-hoc exploratory subgroup analyses evaluated outcomes by background medication and insulin regimen subgroups. METHODS: Data from patients in the PIONEER 3–5, 7 and 8 trials receiving once-daily oral semaglutide (14 mg/flexibly dosed) or a comparator (placebo, sitagliptin 100 mg or liraglutide 1.8 mg) were analysed for efficacy (glycated haemoglobin [HbA(1c)] and body weight changes from baseline to planned end of treatment) and safety outcomes. Patients were grouped according to background medication (metformin, sulphonylurea, thiazolidinedione, sodium-glucose cotransporter-2 inhibitor, insulin, or combinations thereof). Efficacy outcomes were analysed using the trial product estimand (which assumes that patients remained on the trial product without rescue medication use). A separate analysis by background insulin regimen (basal, premixed or basal-bolus) was done for PIONEER 8 using the treatment policy estimand (regardless of trial product discontinuation or rescue medication use). Safety outcomes were analysed descriptively for all patients. RESULTS: In total, 2836 patients receiving oral semaglutide 14 mg/flexibly dosed or comparators were included. Baseline characteristics were generally similar across background medication subgroups within each trial. Diabetes duration tended to be longer in patients receiving more background medications. Greater HbA(1c) and body weight reductions were seen across background medication subgroups with oral semaglutide (changes from baseline: − 1.0 to − 1.5% and − 2.2 to − 5.0 kg, respectively) than with comparators (except for similar HbA(1c) reductions vs liraglutide). There were no statistically significant interactions by treatment and background medication subgroup for change in HbA(1c) or body weight except for change in HbA(1c) (background insulin vs insulin plus metformin) in PIONEER 8 (p = 0.0408). Changes in HbA(1c) and body weight were generally similar across insulin regimen subgroups, without significant treatment interactions by subgroup, and the total daily insulin dose was decreased for patients receiving oral semaglutide. The incidence of adverse events was generally similar in background medication subgroups. CONCLUSION: Oral semaglutide was effective at lowering HbA(1c) and body weight, regardless of background medications, and appears suitable for a broad range of patients with T2D in combination with other glucose-lowering agents. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02607865 (PIONEER 3), NCT02863419 (PIONEER 4), NCT02827708 (PIONEER 5), NCT02849080 (PIONEER 7) and NCT03021187 (PIONEER 8). GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13300-020-00994-9. Springer Healthcare 2021-03-04 2021-04 /pmc/articles/PMC7994454/ /pubmed/33660198 http://dx.doi.org/10.1007/s13300-020-00994-9 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Original Research
Pratley, Richard E.
Crowley, Matthew J.
Gislum, Mette
Hertz, Christin L.
Jensen, Thomas B.
Khunti, Kamlesh
Mosenzon, Ofri
Buse, John B.
Oral Semaglutide Reduces HbA(1c) and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses
title Oral Semaglutide Reduces HbA(1c) and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses
title_full Oral Semaglutide Reduces HbA(1c) and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses
title_fullStr Oral Semaglutide Reduces HbA(1c) and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses
title_full_unstemmed Oral Semaglutide Reduces HbA(1c) and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses
title_short Oral Semaglutide Reduces HbA(1c) and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses
title_sort oral semaglutide reduces hba(1c) and body weight in patients with type 2 diabetes regardless of background glucose-lowering medication: pioneer subgroup analyses
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994454/
https://www.ncbi.nlm.nih.gov/pubmed/33660198
http://dx.doi.org/10.1007/s13300-020-00994-9
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