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
| العنوان: | 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 |
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| المؤلفون: | Robert Silver, G Bedel, M Yanovskaya, Simon Heller, T Hart, A Golovach, G Cornett, A Luts, A Chang, L Lewy-Alterbaum, H Nguyen, S Hasan, Amir Tirosh, W Biggs, R Pratley, K Blaze, Ole Holm Hels, A Peskov, P Houser, E Klein, Peter Rossing, H Knoble, T Milovanova, P O'Donnell, S Folkerth, H A Frandsen, S Chandran, A Krzeminski, Richard E. Pratley, J Reed, S Sulosaari, Torben Hansen, T Donner, Jan W. Eriksson, R Jackson, N Krasnopeeva, J Pouzar, E Kazakova, J Gumprecht, Thalia Marie Blicher, E Morawski, S Nieminen, Y Shlesinger, J Parker, Klaus Levin, T Maxwell, Z Shaikh, A Nikkola, E Zhdanova, D Nabriski, T Lysenko, P Norwood, G Vagapova, K Khan, J Eriksson, M Hellgren, Ofri Mosenzon, John Strand, M Hewitt, Naim Shehadeh, B Barker, E Haddad, K Eliasson, Y Pergaeva, T Sathyapalan, M Kunitsyna, Thozhukat Sathyapalan, W Gandy, J Soufer, S Chilka, J Lawhead, P Nicol, M Benson, A Odugbesan, S Aronoff, G Gatipon, R Abramof, L Gonzalez-Orozco, C Desouza, O Mosenzon, I Beshay, H Traylor, B Snyder, Robert S. Lindsay, A Cleland, K Metsärinne, Paweł Bogdański, K Forshaw, M Sergeeva-Kondrachenko, Cyrus Desouza, M Hitz, S Plevin, K Astamirova, N Uhlenius, R Huntley, D Alpenidze, B Delgado, L Zarutskaya, Signe Rosenlund, John A. McKnight, P Levin, E Frolova, S Heller, P E Jakobsen, A Kapoor, R Busch, S Chaidarun, L Connery, S Hietaniemi, Sten Madsbad, M. Shamkhalova, S Lindmark, B Hella, L Belousova, C Mbogua, L Kargina |
| المصدر: | Mosenzon, O, Blicher, T M, Rosenlund, S, Eriksson, J W, Heller, S, Hels, O H, Pratley, R, Sathyapalan, T, Desouza, C, PIONEER 5 Investigators, 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, Hansen, T K, Hitz, M, Jakobsen, P E, Levin, K, Madsbad, S, Nguyen, H, Parker, J, Reed, J, Rossing, P, Yanovskaya, M, Zarutskaya, L & 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 ', The Lancet Diabetes and Endocrinology, vol. 7, no. 7, pp. 515-527 . https://doi.org/10.1016/S2213-8587Test(19)30192-5 Mosenzon, O, Blicher, T M, Rosenlund, S, Eriksson, J W, Heller, S, Hels, O H, Pratley, R, Sathyapalan, T, Desouza, C & PIONEER 5 Investigators 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 ', The Lancet Diabetes & Endocrinology, vol. 7, no. 7, pp. 515-527 . https://doi.org/10.1016/S2213-8587Test(19)30192-5 |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, Glucagon-Like Peptides, Administration, Oral, 030209 endocrinology & metabolism, Type 2 diabetes, Placebo, Glucagon-Like Peptide-1 Receptor, law.invention, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Internal Medicine, medicine, Clinical endpoint, Humans, Diabetic Nephropathies, Renal Insufficiency, 030212 general & internal medicine, education, Aged, education.field_of_study, business.industry, Semaglutide, Middle Aged, medicine.disease, Discontinuation, Clinical trial, Treatment Outcome, Diabetes Mellitus, Type 2, Female, business |
| الوصف: | 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. Findings: Between Sept 20, 2016, and Sept 29, 2017, of 721 patients screened, 324 were eligible and randomly assigned to oral semaglutide (n=163) or placebo (n=161). Mean age at baseline was 70 years (SD 8), and 168 (52%) of participants were female. 133 (82%) participants in the oral semaglutide group and 141 (88%) in the placebo group completed 26 weeks on treatment. At 26 weeks, oral semaglutide was superior to placebo in decreasing HbA1c (estimated mean change of −1·0 percentage point (SE 0·1; −11 mmol/mol [SE 0·8]) vs −0·2 percentage points (SE 0·1; −2 mmol/mol [SE 0·8]); estimated treatment difference [ETD]: −0·8 percentage points, 95% CI −1·0 to −0·6; p1c −1·1 percentage points (SE 0·1; −12 mmol/mol [SE 0·8] versus −0·1 percentage points (SE 0·1; −1 mmol/mol [SE 0·8]; ETD −1·0 percentage points, 95% CI −1·2 to −0·8; p |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2213-8587 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6d569511b15de88f728dd8364203edd9Test https://curis.ku.dk/ws/files/251035512/Efficacy_and_safety_of_oral_semaglutide_in_patients_with_type_2_diabetes_and_moderate_renal_impairment_PIONEER_5_accepted_version_.pdfTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6d569511b15de88f728dd8364203edd9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22138587 |
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