Effect of liraglutide on ambulatory blood pressure in patients with hypertension and type 2 diabetes: A randomized, double‐blind, placebo‐controlled trial

Aims To assess the effect of liraglutide on 24‐hour ambulatory blood pressure and heart rate in patients with hypertension (pre‐ and stage 1 hypertension) and inadequately controlled Type 2 diabetes (glycated haemoglobin 7%–10% [53‐86 mmol/mol]). Materials and methods Eligible patients for this inve...

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Veröffentlicht in:Diabetes, obesity & metabolism obesity & metabolism, 2019-03, Vol.21 (3), p.517-524
Hauptverfasser: Liakos, Aris, Lambadiari, Vaia, Bargiota, Alexandra, Kitsios, Konstantinos, Avramidis, Iakovos, Kotsa, Kalliopi, Gerou, Spyridon, Boura, Panagiota, Tentolouris, Nikolaos, Dimitriadis, George, Tsapas, Apostolos
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container_end_page 524
container_issue 3
container_start_page 517
container_title Diabetes, obesity & metabolism
container_volume 21
creator Liakos, Aris
Lambadiari, Vaia
Bargiota, Alexandra
Kitsios, Konstantinos
Avramidis, Iakovos
Kotsa, Kalliopi
Gerou, Spyridon
Boura, Panagiota
Tentolouris, Nikolaos
Dimitriadis, George
Tsapas, Apostolos
description Aims To assess the effect of liraglutide on 24‐hour ambulatory blood pressure and heart rate in patients with hypertension (pre‐ and stage 1 hypertension) and inadequately controlled Type 2 diabetes (glycated haemoglobin 7%–10% [53‐86 mmol/mol]). Materials and methods Eligible patients for this investigator‐initiated, parallel‐group, randomized, double‐blind trial were on stable background antihyperglycaemic therapy excluding insulin, glucagon‐like peptide‐1 receptor agonists and dipeptidyl‐peptidase‐4 inhibitors. Participants were centrally randomized in a 1:1 ratio to daily liraglutide 0.6 mg, titrated to 1.2 mg after the first week, or placebo for 5 weeks. The primary outcome was change in 24‐hour ambulatory systolic blood pressure (SBP), and secondary outcomes included change in ambulatory diastolic blood pressure (DBP) and heart rate. We also assessed renal sodium handling. Results Of 87 patients assessed for eligibility, 62 (66.1% men) with a mean age of 60.2 years were randomized to liraglutide (n = 31) or placebo (n = 31). All participants received background therapy with metformin, whilst 35.5% were treated concomitantly with sulphonylureas and 14.5% with pioglitazone. Compared with placebo, liraglutide reduced 24‐hour SBP by −5.73 mm Hg (95% confidence interval [CI] –9.81 to −1.65) and had a neutral effect on 24‐hour DBP (mean difference − 1.42 mm Hg; 95% CI –4.25 to 1.40), whilst increasing 24‐hour heart rate by 6.16 beats/min (95% CI 3.25 to 9.07). Findings were consistent for daytime and night‐time measurements. Liraglutide did not increase urine sodium excretion. Conclusion Based on 24‐hour ambulatory measurements, short‐term treatment with liraglutide had a favourable effect on SBP whilst increasing heart rate.
doi_str_mv 10.1111/dom.13541
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Materials and methods Eligible patients for this investigator‐initiated, parallel‐group, randomized, double‐blind trial were on stable background antihyperglycaemic therapy excluding insulin, glucagon‐like peptide‐1 receptor agonists and dipeptidyl‐peptidase‐4 inhibitors. Participants were centrally randomized in a 1:1 ratio to daily liraglutide 0.6 mg, titrated to 1.2 mg after the first week, or placebo for 5 weeks. The primary outcome was change in 24‐hour ambulatory systolic blood pressure (SBP), and secondary outcomes included change in ambulatory diastolic blood pressure (DBP) and heart rate. We also assessed renal sodium handling. Results Of 87 patients assessed for eligibility, 62 (66.1% men) with a mean age of 60.2 years were randomized to liraglutide (n = 31) or placebo (n = 31). All participants received background therapy with metformin, whilst 35.5% were treated concomitantly with sulphonylureas and 14.5% with pioglitazone. Compared with placebo, liraglutide reduced 24‐hour SBP by −5.73 mm Hg (95% confidence interval [CI] –9.81 to −1.65) and had a neutral effect on 24‐hour DBP (mean difference − 1.42 mm Hg; 95% CI –4.25 to 1.40), whilst increasing 24‐hour heart rate by 6.16 beats/min (95% CI 3.25 to 9.07). Findings were consistent for daytime and night‐time measurements. Liraglutide did not increase urine sodium excretion. Conclusion Based on 24‐hour ambulatory measurements, short‐term treatment with liraglutide had a favourable effect on SBP whilst increasing heart rate.</description><identifier>ISSN: 1462-8902</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.13541</identifier><identifier>PMID: 30242948</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Aged ; Antidiabetics ; Blood Glucose - drug effects ; Blood pressure ; Blood Pressure - drug effects ; Blood Pressure Monitoring, Ambulatory ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - physiopathology ; Dipeptidyl-peptidase IV ; Double-Blind Method ; Double-blind studies ; Evidence-based medicine ; Excretion ; Female ; GLP-1 receptor agonists ; GLP‐1 ; Glucagon ; Heart rate ; Heart Rate - drug effects ; Hemoglobin ; Humans ; Hypertension ; Hypertension - blood ; Hypertension - complications ; Hypertension - drug therapy ; Insulin ; Lipids - blood ; liraglutide ; Liraglutide - pharmacology ; Liraglutide - therapeutic use ; Male ; Metformin ; Middle Aged ; Patients ; Peptidase ; Pioglitazone ; Placebos ; randomized trial ; Renal function ; Sodium ; type 2 diabetes ; Urine</subject><ispartof>Diabetes, obesity &amp; metabolism, 2019-03, Vol.21 (3), p.517-524</ispartof><rights>2018 John Wiley &amp; Sons Ltd</rights><rights>2018 John Wiley &amp; Sons Ltd.</rights><rights>2019 John Wiley &amp; Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3531-6bb283833226f8007dabe43a8c45f0537f7fef176faaf880be2691ceac9660c23</citedby><cites>FETCH-LOGICAL-c3531-6bb283833226f8007dabe43a8c45f0537f7fef176faaf880be2691ceac9660c23</cites><orcidid>0000-0003-3261-2979 ; 0000-0003-0221-4072</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdom.13541$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdom.13541$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30242948$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liakos, Aris</creatorcontrib><creatorcontrib>Lambadiari, Vaia</creatorcontrib><creatorcontrib>Bargiota, Alexandra</creatorcontrib><creatorcontrib>Kitsios, Konstantinos</creatorcontrib><creatorcontrib>Avramidis, Iakovos</creatorcontrib><creatorcontrib>Kotsa, Kalliopi</creatorcontrib><creatorcontrib>Gerou, Spyridon</creatorcontrib><creatorcontrib>Boura, Panagiota</creatorcontrib><creatorcontrib>Tentolouris, Nikolaos</creatorcontrib><creatorcontrib>Dimitriadis, George</creatorcontrib><creatorcontrib>Tsapas, Apostolos</creatorcontrib><title>Effect of liraglutide on ambulatory blood pressure in patients with hypertension and type 2 diabetes: A randomized, double‐blind, placebo‐controlled trial</title><title>Diabetes, obesity &amp; metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aims To assess the effect of liraglutide on 24‐hour ambulatory blood pressure and heart rate in patients with hypertension (pre‐ and stage 1 hypertension) and inadequately controlled Type 2 diabetes (glycated haemoglobin 7%–10% [53‐86 mmol/mol]). Materials and methods Eligible patients for this investigator‐initiated, parallel‐group, randomized, double‐blind trial were on stable background antihyperglycaemic therapy excluding insulin, glucagon‐like peptide‐1 receptor agonists and dipeptidyl‐peptidase‐4 inhibitors. Participants were centrally randomized in a 1:1 ratio to daily liraglutide 0.6 mg, titrated to 1.2 mg after the first week, or placebo for 5 weeks. The primary outcome was change in 24‐hour ambulatory systolic blood pressure (SBP), and secondary outcomes included change in ambulatory diastolic blood pressure (DBP) and heart rate. We also assessed renal sodium handling. Results Of 87 patients assessed for eligibility, 62 (66.1% men) with a mean age of 60.2 years were randomized to liraglutide (n = 31) or placebo (n = 31). All participants received background therapy with metformin, whilst 35.5% were treated concomitantly with sulphonylureas and 14.5% with pioglitazone. Compared with placebo, liraglutide reduced 24‐hour SBP by −5.73 mm Hg (95% confidence interval [CI] –9.81 to −1.65) and had a neutral effect on 24‐hour DBP (mean difference − 1.42 mm Hg; 95% CI –4.25 to 1.40), whilst increasing 24‐hour heart rate by 6.16 beats/min (95% CI 3.25 to 9.07). Findings were consistent for daytime and night‐time measurements. Liraglutide did not increase urine sodium excretion. Conclusion Based on 24‐hour ambulatory measurements, short‐term treatment with liraglutide had a favourable effect on SBP whilst increasing heart rate.</description><subject>Aged</subject><subject>Antidiabetics</subject><subject>Blood Glucose - drug effects</subject><subject>Blood pressure</subject><subject>Blood Pressure - drug effects</subject><subject>Blood Pressure Monitoring, Ambulatory</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - physiopathology</subject><subject>Dipeptidyl-peptidase IV</subject><subject>Double-Blind Method</subject><subject>Double-blind studies</subject><subject>Evidence-based medicine</subject><subject>Excretion</subject><subject>Female</subject><subject>GLP-1 receptor agonists</subject><subject>GLP‐1</subject><subject>Glucagon</subject><subject>Heart rate</subject><subject>Heart Rate - drug effects</subject><subject>Hemoglobin</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertension - blood</subject><subject>Hypertension - complications</subject><subject>Hypertension - drug therapy</subject><subject>Insulin</subject><subject>Lipids - blood</subject><subject>liraglutide</subject><subject>Liraglutide - pharmacology</subject><subject>Liraglutide - therapeutic use</subject><subject>Male</subject><subject>Metformin</subject><subject>Middle Aged</subject><subject>Patients</subject><subject>Peptidase</subject><subject>Pioglitazone</subject><subject>Placebos</subject><subject>randomized trial</subject><subject>Renal function</subject><subject>Sodium</subject><subject>type 2 diabetes</subject><subject>Urine</subject><issn>1462-8902</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctOVTEUhhuiAUQHvABp4kQTN_SyLz3OCOIlgTDR8U4vq1LS3W7a7pDjyEfwCXw4n8QeDjgwoZO2K1-_1fwLoUNKjmldJyZOx5R3Ld1B-7TteUM565_dn1kjVoTtoRc53xBCWi6GXbTHCWvZqhX76Pe5taALjhZ7l-R3vxRnAMeA5aQWL0tMa6x8jAbPCXJeEmAX8CyLg1AyvnPlGl-vZ0gFQnabd8HgUguYYeOkggL5PT7Fqdbj5H6AeYdNXJSHPz9_Ke9Cvc9ealCxFnQMJUXvoTqSk_4lem6lz_DqYT9A3z6efz373FxcffpydnrRaN5x2vRKMcEF54z1VhAymNq45VLotrOk44MdLFg69FZKKwRRwPoV1SD1qu-JZvwAvdl65xRvF8hlnFzW4L0MEJc8sk3ONTLaVfT1f-hNXFKov6vUMBAqBs4r9XZL6RRzTmDHOblJpvVIybiRjTWN8X5olT16MC5qAvOPfJxSBU62wJ3zsH7aNH64utwq_wJNLaTF</recordid><startdate>201903</startdate><enddate>201903</enddate><creator>Liakos, Aris</creator><creator>Lambadiari, Vaia</creator><creator>Bargiota, Alexandra</creator><creator>Kitsios, Konstantinos</creator><creator>Avramidis, Iakovos</creator><creator>Kotsa, Kalliopi</creator><creator>Gerou, Spyridon</creator><creator>Boura, Panagiota</creator><creator>Tentolouris, Nikolaos</creator><creator>Dimitriadis, George</creator><creator>Tsapas, Apostolos</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3261-2979</orcidid><orcidid>https://orcid.org/0000-0003-0221-4072</orcidid></search><sort><creationdate>201903</creationdate><title>Effect of liraglutide on ambulatory blood pressure in patients with hypertension and type 2 diabetes: A randomized, double‐blind, placebo‐controlled trial</title><author>Liakos, Aris ; Lambadiari, Vaia ; Bargiota, Alexandra ; Kitsios, Konstantinos ; Avramidis, Iakovos ; Kotsa, Kalliopi ; Gerou, Spyridon ; Boura, Panagiota ; Tentolouris, Nikolaos ; Dimitriadis, George ; Tsapas, Apostolos</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3531-6bb283833226f8007dabe43a8c45f0537f7fef176faaf880be2691ceac9660c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aged</topic><topic>Antidiabetics</topic><topic>Blood Glucose - drug effects</topic><topic>Blood pressure</topic><topic>Blood Pressure - drug effects</topic><topic>Blood Pressure Monitoring, Ambulatory</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - physiopathology</topic><topic>Dipeptidyl-peptidase IV</topic><topic>Double-Blind Method</topic><topic>Double-blind studies</topic><topic>Evidence-based medicine</topic><topic>Excretion</topic><topic>Female</topic><topic>GLP-1 receptor agonists</topic><topic>GLP‐1</topic><topic>Glucagon</topic><topic>Heart rate</topic><topic>Heart Rate - drug effects</topic><topic>Hemoglobin</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypertension - blood</topic><topic>Hypertension - complications</topic><topic>Hypertension - drug therapy</topic><topic>Insulin</topic><topic>Lipids - blood</topic><topic>liraglutide</topic><topic>Liraglutide - pharmacology</topic><topic>Liraglutide - therapeutic use</topic><topic>Male</topic><topic>Metformin</topic><topic>Middle Aged</topic><topic>Patients</topic><topic>Peptidase</topic><topic>Pioglitazone</topic><topic>Placebos</topic><topic>randomized trial</topic><topic>Renal function</topic><topic>Sodium</topic><topic>type 2 diabetes</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liakos, Aris</creatorcontrib><creatorcontrib>Lambadiari, Vaia</creatorcontrib><creatorcontrib>Bargiota, Alexandra</creatorcontrib><creatorcontrib>Kitsios, Konstantinos</creatorcontrib><creatorcontrib>Avramidis, Iakovos</creatorcontrib><creatorcontrib>Kotsa, Kalliopi</creatorcontrib><creatorcontrib>Gerou, Spyridon</creatorcontrib><creatorcontrib>Boura, Panagiota</creatorcontrib><creatorcontrib>Tentolouris, Nikolaos</creatorcontrib><creatorcontrib>Dimitriadis, George</creatorcontrib><creatorcontrib>Tsapas, Apostolos</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes, obesity &amp; metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liakos, Aris</au><au>Lambadiari, Vaia</au><au>Bargiota, Alexandra</au><au>Kitsios, Konstantinos</au><au>Avramidis, Iakovos</au><au>Kotsa, Kalliopi</au><au>Gerou, Spyridon</au><au>Boura, Panagiota</au><au>Tentolouris, Nikolaos</au><au>Dimitriadis, George</au><au>Tsapas, Apostolos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of liraglutide on ambulatory blood pressure in patients with hypertension and type 2 diabetes: A randomized, double‐blind, placebo‐controlled trial</atitle><jtitle>Diabetes, obesity &amp; metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2019-03</date><risdate>2019</risdate><volume>21</volume><issue>3</issue><spage>517</spage><epage>524</epage><pages>517-524</pages><issn>1462-8902</issn><eissn>1463-1326</eissn><abstract>Aims To assess the effect of liraglutide on 24‐hour ambulatory blood pressure and heart rate in patients with hypertension (pre‐ and stage 1 hypertension) and inadequately controlled Type 2 diabetes (glycated haemoglobin 7%–10% [53‐86 mmol/mol]). Materials and methods Eligible patients for this investigator‐initiated, parallel‐group, randomized, double‐blind trial were on stable background antihyperglycaemic therapy excluding insulin, glucagon‐like peptide‐1 receptor agonists and dipeptidyl‐peptidase‐4 inhibitors. Participants were centrally randomized in a 1:1 ratio to daily liraglutide 0.6 mg, titrated to 1.2 mg after the first week, or placebo for 5 weeks. The primary outcome was change in 24‐hour ambulatory systolic blood pressure (SBP), and secondary outcomes included change in ambulatory diastolic blood pressure (DBP) and heart rate. We also assessed renal sodium handling. Results Of 87 patients assessed for eligibility, 62 (66.1% men) with a mean age of 60.2 years were randomized to liraglutide (n = 31) or placebo (n = 31). All participants received background therapy with metformin, whilst 35.5% were treated concomitantly with sulphonylureas and 14.5% with pioglitazone. Compared with placebo, liraglutide reduced 24‐hour SBP by −5.73 mm Hg (95% confidence interval [CI] –9.81 to −1.65) and had a neutral effect on 24‐hour DBP (mean difference − 1.42 mm Hg; 95% CI –4.25 to 1.40), whilst increasing 24‐hour heart rate by 6.16 beats/min (95% CI 3.25 to 9.07). Findings were consistent for daytime and night‐time measurements. Liraglutide did not increase urine sodium excretion. Conclusion Based on 24‐hour ambulatory measurements, short‐term treatment with liraglutide had a favourable effect on SBP whilst increasing heart rate.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>30242948</pmid><doi>10.1111/dom.13541</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-3261-2979</orcidid><orcidid>https://orcid.org/0000-0003-0221-4072</orcidid></addata></record>
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subjects Aged
Antidiabetics
Blood Glucose - drug effects
Blood pressure
Blood Pressure - drug effects
Blood Pressure Monitoring, Ambulatory
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - physiopathology
Dipeptidyl-peptidase IV
Double-Blind Method
Double-blind studies
Evidence-based medicine
Excretion
Female
GLP-1 receptor agonists
GLP‐1
Glucagon
Heart rate
Heart Rate - drug effects
Hemoglobin
Humans
Hypertension
Hypertension - blood
Hypertension - complications
Hypertension - drug therapy
Insulin
Lipids - blood
liraglutide
Liraglutide - pharmacology
Liraglutide - therapeutic use
Male
Metformin
Middle Aged
Patients
Peptidase
Pioglitazone
Placebos
randomized trial
Renal function
Sodium
type 2 diabetes
Urine
title Effect of liraglutide on ambulatory blood pressure in patients with hypertension and type 2 diabetes: A randomized, double‐blind, placebo‐controlled trial
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