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Differential Effects of DPP-4 Inhibitors, Anagliptin and Sitagliptin, on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy
Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Treatment with a statin leads to a compensatory increase in circulating PCSK9 level. Anagliptin, a dipeptidyl peptidase-4 (DPP-4) i...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Japan Atherosclerosis Society
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8737073/ https://www.ncbi.nlm.nih.gov/pubmed/33342939 http://dx.doi.org/10.5551/jat.58396 |
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author | Furuhashi, Masato Sakuma, Ichiro Morimoto, Takeshi Higashiura, Yukimura Sakai, Akiko Matsumoto, Megumi Sakuma, Mio Shimabukuro, Michio Nomiyama, Takashi Arasaki, Osamu Node, Koichi Ueda, Shinichiro |
author_facet | Furuhashi, Masato Sakuma, Ichiro Morimoto, Takeshi Higashiura, Yukimura Sakai, Akiko Matsumoto, Megumi Sakuma, Mio Shimabukuro, Michio Nomiyama, Takashi Arasaki, Osamu Node, Koichi Ueda, Shinichiro |
author_sort | Furuhashi, Masato |
collection | PubMed |
description | Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Treatment with a statin leads to a compensatory increase in circulating PCSK9 level. Anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to decrease LDL cholesterol (LDL-C) levels to a greater extent than that by sitagliptin, another DPP-4 inhibitor, in the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. We investigated PCSK9 concentration in type 2 diabetes mellitus (T2DM) and the impact of treatment with anagliptin or sitagliptin on PCSK9 level as a sub-analysis of the REASON trial. Methods: PCSK9 concentration was measured at baseline and after 52 weeks of treatment with anagliptin ( n =122) or sitagliptin ( n =128) in patients with T2DM who were receiving statin therapy. All of the included patients had been treated with a DPP-4 inhibitor prior to randomization. Results: Baseline PCSK9 level was positively, but not significantly, correlated with LDL-C and was independently associated with platelet count and level of triglycerides. Concomitant with reduction of LDL-C, but not hemoglobin A1c (HbA1c), by anagliptin, PCSK9 level was significantly increased by treatment with sitagliptin (218±98 vs. 242±115 ng/mL, P =0.01), but not anagliptin (233±97 vs. 250±106 ng/mL, P =0.07). Conclusions: PCSK9 level is independently associated with platelet count and level of triglycerides, but not LDL-C, in patients with T2DM. Anagliptin reduces LDL-C level independent of HbA1c control in patients with T2DM who are on statin therapy possibly by suppressing excess statin-mediated PCSK9 induction and subsequent degradation of the LDL receptor. |
format | Online Article Text |
id | pubmed-8737073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Japan Atherosclerosis Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-87370732022-01-25 Differential Effects of DPP-4 Inhibitors, Anagliptin and Sitagliptin, on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy Furuhashi, Masato Sakuma, Ichiro Morimoto, Takeshi Higashiura, Yukimura Sakai, Akiko Matsumoto, Megumi Sakuma, Mio Shimabukuro, Michio Nomiyama, Takashi Arasaki, Osamu Node, Koichi Ueda, Shinichiro J Atheroscler Thromb Original Article Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Treatment with a statin leads to a compensatory increase in circulating PCSK9 level. Anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to decrease LDL cholesterol (LDL-C) levels to a greater extent than that by sitagliptin, another DPP-4 inhibitor, in the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. We investigated PCSK9 concentration in type 2 diabetes mellitus (T2DM) and the impact of treatment with anagliptin or sitagliptin on PCSK9 level as a sub-analysis of the REASON trial. Methods: PCSK9 concentration was measured at baseline and after 52 weeks of treatment with anagliptin ( n =122) or sitagliptin ( n =128) in patients with T2DM who were receiving statin therapy. All of the included patients had been treated with a DPP-4 inhibitor prior to randomization. Results: Baseline PCSK9 level was positively, but not significantly, correlated with LDL-C and was independently associated with platelet count and level of triglycerides. Concomitant with reduction of LDL-C, but not hemoglobin A1c (HbA1c), by anagliptin, PCSK9 level was significantly increased by treatment with sitagliptin (218±98 vs. 242±115 ng/mL, P =0.01), but not anagliptin (233±97 vs. 250±106 ng/mL, P =0.07). Conclusions: PCSK9 level is independently associated with platelet count and level of triglycerides, but not LDL-C, in patients with T2DM. Anagliptin reduces LDL-C level independent of HbA1c control in patients with T2DM who are on statin therapy possibly by suppressing excess statin-mediated PCSK9 induction and subsequent degradation of the LDL receptor. Japan Atherosclerosis Society 2022-01-01 2020-12-18 /pmc/articles/PMC8737073/ /pubmed/33342939 http://dx.doi.org/10.5551/jat.58396 Text en 2022 Japan Atherosclerosis Society https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.http://creativecommons.org/licenses/by-nc-sa/4.0/ (https://creativecommons.org/licenses/by-nc-sa/4.0/) |
spellingShingle | Original Article Furuhashi, Masato Sakuma, Ichiro Morimoto, Takeshi Higashiura, Yukimura Sakai, Akiko Matsumoto, Megumi Sakuma, Mio Shimabukuro, Michio Nomiyama, Takashi Arasaki, Osamu Node, Koichi Ueda, Shinichiro Differential Effects of DPP-4 Inhibitors, Anagliptin and Sitagliptin, on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy |
title | Differential Effects of DPP-4 Inhibitors, Anagliptin and Sitagliptin, on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy |
title_full | Differential Effects of DPP-4 Inhibitors, Anagliptin and Sitagliptin, on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy |
title_fullStr | Differential Effects of DPP-4 Inhibitors, Anagliptin and Sitagliptin, on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy |
title_full_unstemmed | Differential Effects of DPP-4 Inhibitors, Anagliptin and Sitagliptin, on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy |
title_short | Differential Effects of DPP-4 Inhibitors, Anagliptin and Sitagliptin, on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy |
title_sort | differential effects of dpp-4 inhibitors, anagliptin and sitagliptin, on pcsk9 levels in patients with type 2 diabetes mellitus who are receiving statin therapy |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8737073/ https://www.ncbi.nlm.nih.gov/pubmed/33342939 http://dx.doi.org/10.5551/jat.58396 |
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