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Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial

Mosenzon, Ofri; Blicher, Thalia Marie; Rosenlund, Signe; Eriksson, Jan W; Heller, Simon; Hels, Ole Holm; Pratley, Richard; Sathyapalan, Thozhukat; Desouza, Cyrus; Abramof, R; Alpenidze, D; Aronoff, S; Astamirova, K; Barker, B; Bedel, G; Belousova, L; Benson, M; Beshay, I; Biggs, W; Blaze, K; Bogdanski, P; Busch, R; Chaidarun, S; Chandran, S; Chang, A; Chilka, S; Cleland, A; Connery, L; Cornett, G; Delgado, B; Desouza, C; Donner, T; Eliasson, K; Eriksson, J; Folkerth, S; Forshaw, K; Frandsen, H A; Frolova, E; Gandy, W; Gatipon, G; Golovach, A; Gonzalez-Orozco, L; Gumprecht, J; Haddad, E; Hansen, T K; Hart, T; Hasan, S; Hella, B; Heller, S; Hellgren, M; Hewitt, M; Hietaniemi, S; Hitz, M; Houser, P; Huntley, R; Jackson, R; Jakobsen, P E; Kapoor, A; Kargina, L; Kazakova, E; Khan, K; Klein, E; Knoble, H; Krasnopeeva (Kabachkova), N; Krzeminski, A; Kunitsyna, M; Lawhead, J; Levin, K; Levin, P; Lewy-Alterbaum, L; Lindmark, S; Lindsay, R; Luts, A; Lysenko, T; Madsbad, S; Maxwell, T; Mbogua, C; Mcknight, J; Metsärinne, K; Milovanova, T; Morawski, E; Mosenzon, O; Nabriski, D; Nguyen, H; Nicol, P; Nieminen, S; Nikkola, A; Norwood, P; O'Donnell, P; Odugbesan, A; Parker, J; Pergaeva, Y; Peskov, A; Plevin, S; Pouzar, J; Pratley, R; Reed, J; Rossing, P; Sathyapalan, T; Sergeeva-Kondrachenko, M; Shaikh, Z; Shamkhalova, M; Shehadeh, N; Shlesinger, Y; Silver, R; Snyder, B; Soufer, J; Strand, J; Sulosaari, S; Tirosh, A; Traylor, H; Uhlenius, N; Vagapova, G; Yanovskaya, M; Zarutskaya, L; Zhdanova, E

Authors

Ofri Mosenzon

Thalia Marie Blicher

Signe Rosenlund

Jan W Eriksson

Simon Heller

Ole Holm Hels

Richard Pratley

Thozhukat Sathyapalan

Cyrus Desouza

R Abramof

D Alpenidze

S Aronoff

K Astamirova

B Barker

G Bedel

L Belousova

M Benson

I Beshay

W Biggs

K Blaze

P Bogdanski

R Busch

S Chaidarun

S Chandran

A Chang

S Chilka

A Cleland

L Connery

G Cornett

B Delgado

C Desouza

T Donner

K Eliasson

J Eriksson

S Folkerth

K Forshaw

H A Frandsen

E Frolova

W Gandy

G Gatipon

A Golovach

L Gonzalez-Orozco

J Gumprecht

E Haddad

T K Hansen

T Hart

S Hasan

B Hella

S Heller

M Hellgren

M Hewitt

S Hietaniemi

M Hitz

P Houser

R Huntley

R Jackson

P E Jakobsen

A Kapoor

L Kargina

E Kazakova

K Khan

E Klein

H Knoble

N Krasnopeeva (Kabachkova)

A Krzeminski

M Kunitsyna

J Lawhead

K Levin

P Levin

L Lewy-Alterbaum

S Lindmark

R Lindsay

A Luts

T Lysenko

S Madsbad

T Maxwell

C Mbogua

J Mcknight

K Metsärinne

T Milovanova

E Morawski

O Mosenzon

D Nabriski

H Nguyen

P Nicol

S Nieminen

A Nikkola

P Norwood

P O'Donnell

A Odugbesan

J Parker

Y Pergaeva

A Peskov

S Plevin

J Pouzar

R Pratley

J Reed

P Rossing

T Sathyapalan

M Sergeeva-Kondrachenko

Z Shaikh

M Shamkhalova

N Shehadeh

Y Shlesinger

R Silver

B Snyder

J Soufer

J Strand

S Sulosaari

A Tirosh

H Traylor

N Uhlenius

G Vagapova

M Yanovskaya

L Zarutskaya

E Zhdanova

Abstract

Background
Oral semaglutide is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for glycaemic control in patients with type 2 diabetes. Type 2 diabetes is commonly associated with renal impairment, restricting treatment options. We aimed to investigate the efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment.

Methods
This randomised, double-blind, phase 3a trial was undertaken at 88 sites in eight countries. Patients aged 18 years and older, with type 2 diabetes, an estimated glomerular filtration rate of 30–59 mL/min per 1·73 m2, and who had been receiving a stable dose of metformin or sulfonylurea, or both, or basal insulin with or without metformin for the past 90 days were eligible. Participants were randomly assigned (1:1) by use of an interactive web-response system, with stratification by glucose-lowering medication and renal function, to receive oral semaglutide (dose escalated to 14 mg once daily) or matching placebo for 26 weeks, in addition to background medication. Participants and site staff were masked to assignment. Two efficacy-related estimands were defined: treatment policy (regardless of treatment discontinuation or rescue medication) and trial product (on treatment without rescue medication) in all participants randomly assigned. Endpoints were change from baseline to week 26 in HbA1c (primary endpoint) and bodyweight (confirmatory secondary endpoint), assessed in all participants with sufficient data. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered on ClinicalTrials.gov, number NCT02827708, and the European Clinical Trials Registry, number EudraCT 2015-005326-19, and is now complete.

Journal Article Type Article
Publication Date 2019-07
Journal The Lancet Diabetes & Endocrinology
Print ISSN 2213-8587
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 7
Issue 7
Pages 515-527
Institution Citation Mosenzon, O., Blicher, T. M., Rosenlund, S., Eriksson, J. W., Heller, S., Hels, O. H., …Zhdanova, E. (2019). Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. Lancet Diabetes and Endocrinology, 7(7), 515-527. https://doi.org/10.1016/s2213-8587%2819%2930192-5
DOI https://doi.org/10.1016/s2213-8587%2819%2930192-5
Keywords Internal Medicine; Endocrinology, Diabetes and Metabolism; Endocrinology
Publisher URL https://www.sciencedirect.com/science/article/abs/pii/S2213858719301925?via%3Dihub

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This file is under embargo until Dec 10, 2019 due to copyright reasons.

Contact T.Sathyapalan@hull.ac.uk to request a copy for personal use.



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