Postprandial renal haemodynamic effects of the dipeptidyl peptidase‐4 inhibitor linagliptin versus the sulphonylurea glimepiride in adults with type 2 diabetes (RENALIS): A predefined substudy of a randomized, double‐blind trial

Aim To determine the effect of the dipeptidyl peptidase‐4 inhibitor linagliptin on postprandial glomerular hyperfiltration compared with the sulphonylurea glimepiride in adults with type 2 diabetes (T2D). Materials and Methods In this predefined substudy within a randomized, double‐blind, parallel‐g...

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Veröffentlicht in:Diabetes, obesity & metabolism obesity & metabolism, 2022-01, Vol.24 (1), p.115-124
Hauptverfasser: Muskiet, Marcel H. A., Tonneijck, Lennart, Smits, Mark M., Kramer, Mark H. H., Ouwens, D. Margriet, Hartmann, Bolette, Holst, Jens J., Danser, A. H. Jan, Joles, Jaap A., Raalte, Daniël H.
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container_end_page 124
container_issue 1
container_start_page 115
container_title Diabetes, obesity & metabolism
container_volume 24
creator Muskiet, Marcel H. A.
Tonneijck, Lennart
Smits, Mark M.
Kramer, Mark H. H.
Ouwens, D. Margriet
Hartmann, Bolette
Holst, Jens J.
Danser, A. H. Jan
Joles, Jaap A.
Raalte, Daniël H.
description Aim To determine the effect of the dipeptidyl peptidase‐4 inhibitor linagliptin on postprandial glomerular hyperfiltration compared with the sulphonylurea glimepiride in adults with type 2 diabetes (T2D). Materials and Methods In this predefined substudy within a randomized, double‐blind, parallel‐group, intervention trial, overweight people with T2D without renal impairment were treated with once‐daily linagliptin 5 mg (N = 10) or glimepiride 1 mg (N = 13) as an add‐on to metformin for 8 weeks. After a standardized liquid protein‐rich meal, the glomerular filtration rate (GFR) and effective renal plasma flow were determined by inulin and para‐aminohippuric acid clearance, respectively, based on timed urine sampling. Intrarenal haemodynamics were estimated using the Gomez equations. Glucoregulatory/vasoactive hormones, urinary pH and fractional excretions (FE) of sodium, potassium and urea were measured. Results Compared with glimepiride, linagliptin increased the postprandial filtration fraction (FF; mean difference 2.1%‐point; P = .016) and estimated glomerular hydraulic pressure (mean difference 3.0 mmHg; P = .050), and tended to increase GFR (P = .08) and estimated efferent renal arteriolar resistance (RE; P = .08) from baseline to week 8. No differences in FE were noted. Glimepiride reduced HbA1c more than linagliptin (mean difference −0.40%; P = .004), without between‐group differences in time‐averaged postprandial glucose levels. In the linagliptin group, change in FF correlated with change in mean arterial pressure (R = 0.807; P = .009) and time‐averaged mean glucagon (R = 0.782; P = .008), but not with changes in glucose, insulin, intact glucagon‐like peptide‐1, renin or FENa. Change in glucagon was associated with change in RE (R = 0.830; P = .003). Conclusions In contrast to our hypothesis, compared with glimepiride, linagliptin does not reduce postprandial hyperfiltration, yet appears to increase FF after meal ingestion by increasing blood pressure or RE.
doi_str_mv 10.1111/dom.14557
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A. ; Tonneijck, Lennart ; Smits, Mark M. ; Kramer, Mark H. H. ; Ouwens, D. Margriet ; Hartmann, Bolette ; Holst, Jens J. ; Danser, A. H. Jan ; Joles, Jaap A. ; Raalte, Daniël H.</creator><creatorcontrib>Muskiet, Marcel H. A. ; Tonneijck, Lennart ; Smits, Mark M. ; Kramer, Mark H. H. ; Ouwens, D. Margriet ; Hartmann, Bolette ; Holst, Jens J. ; Danser, A. H. Jan ; Joles, Jaap A. ; Raalte, Daniël H.</creatorcontrib><description>Aim To determine the effect of the dipeptidyl peptidase‐4 inhibitor linagliptin on postprandial glomerular hyperfiltration compared with the sulphonylurea glimepiride in adults with type 2 diabetes (T2D). Materials and Methods In this predefined substudy within a randomized, double‐blind, parallel‐group, intervention trial, overweight people with T2D without renal impairment were treated with once‐daily linagliptin 5 mg (N = 10) or glimepiride 1 mg (N = 13) as an add‐on to metformin for 8 weeks. After a standardized liquid protein‐rich meal, the glomerular filtration rate (GFR) and effective renal plasma flow were determined by inulin and para‐aminohippuric acid clearance, respectively, based on timed urine sampling. Intrarenal haemodynamics were estimated using the Gomez equations. Glucoregulatory/vasoactive hormones, urinary pH and fractional excretions (FE) of sodium, potassium and urea were measured. Results Compared with glimepiride, linagliptin increased the postprandial filtration fraction (FF; mean difference 2.1%‐point; P = .016) and estimated glomerular hydraulic pressure (mean difference 3.0 mmHg; P = .050), and tended to increase GFR (P = .08) and estimated efferent renal arteriolar resistance (RE; P = .08) from baseline to week 8. No differences in FE were noted. Glimepiride reduced HbA1c more than linagliptin (mean difference −0.40%; P = .004), without between‐group differences in time‐averaged postprandial glucose levels. In the linagliptin group, change in FF correlated with change in mean arterial pressure (R = 0.807; P = .009) and time‐averaged mean glucagon (R = 0.782; P = .008), but not with changes in glucose, insulin, intact glucagon‐like peptide‐1, renin or FENa. Change in glucagon was associated with change in RE (R = 0.830; P = .003). Conclusions In contrast to our hypothesis, compared with glimepiride, linagliptin does not reduce postprandial hyperfiltration, yet appears to increase FF after meal ingestion by increasing blood pressure or RE.</description><identifier>ISSN: 1462-8902</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.14557</identifier><identifier>PMID: 34580975</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Blood Glucose ; Blood pressure ; Body weight ; Clinical trials ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 ; dipeptidyl peptidase‐4 ; Dipeptidyl-peptidase IV ; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases ; Double-Blind Method ; Double-blind studies ; DPP‐4 inhibitor ; Glomerular filtration rate ; Glucagon ; Glycated Hemoglobin A ; Hemodynamics ; Humans ; Hypoglycemic Agents - therapeutic use ; Inhibitor drugs ; Insulin ; linagliptin ; Linagliptin - therapeutic use ; Meals ; Metformin ; Original ; Overweight ; Peptidase ; postrandial hyperfiltration ; Renin ; Sulfonylurea Compounds ; sulphonylurea ; Treatment Outcome ; type 2 diabetes ; Vasoactive agents</subject><ispartof>Diabetes, obesity &amp; metabolism, 2022-01, Vol.24 (1), p.115-124</ispartof><rights>2021 The Authors. published by John Wiley &amp; Sons Ltd.</rights><rights>2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley &amp; Sons Ltd.</rights><rights>2021. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). 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A.</creatorcontrib><creatorcontrib>Tonneijck, Lennart</creatorcontrib><creatorcontrib>Smits, Mark M.</creatorcontrib><creatorcontrib>Kramer, Mark H. H.</creatorcontrib><creatorcontrib>Ouwens, D. Margriet</creatorcontrib><creatorcontrib>Hartmann, Bolette</creatorcontrib><creatorcontrib>Holst, Jens J.</creatorcontrib><creatorcontrib>Danser, A. H. Jan</creatorcontrib><creatorcontrib>Joles, Jaap A.</creatorcontrib><creatorcontrib>Raalte, Daniël H.</creatorcontrib><title>Postprandial renal haemodynamic effects of the dipeptidyl peptidase‐4 inhibitor linagliptin versus the sulphonylurea glimepiride in adults with type 2 diabetes (RENALIS): A predefined substudy of a randomized, double‐blind trial</title><title>Diabetes, obesity &amp; metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aim To determine the effect of the dipeptidyl peptidase‐4 inhibitor linagliptin on postprandial glomerular hyperfiltration compared with the sulphonylurea glimepiride in adults with type 2 diabetes (T2D). Materials and Methods In this predefined substudy within a randomized, double‐blind, parallel‐group, intervention trial, overweight people with T2D without renal impairment were treated with once‐daily linagliptin 5 mg (N = 10) or glimepiride 1 mg (N = 13) as an add‐on to metformin for 8 weeks. After a standardized liquid protein‐rich meal, the glomerular filtration rate (GFR) and effective renal plasma flow were determined by inulin and para‐aminohippuric acid clearance, respectively, based on timed urine sampling. Intrarenal haemodynamics were estimated using the Gomez equations. Glucoregulatory/vasoactive hormones, urinary pH and fractional excretions (FE) of sodium, potassium and urea were measured. Results Compared with glimepiride, linagliptin increased the postprandial filtration fraction (FF; mean difference 2.1%‐point; P = .016) and estimated glomerular hydraulic pressure (mean difference 3.0 mmHg; P = .050), and tended to increase GFR (P = .08) and estimated efferent renal arteriolar resistance (RE; P = .08) from baseline to week 8. No differences in FE were noted. Glimepiride reduced HbA1c more than linagliptin (mean difference −0.40%; P = .004), without between‐group differences in time‐averaged postprandial glucose levels. In the linagliptin group, change in FF correlated with change in mean arterial pressure (R = 0.807; P = .009) and time‐averaged mean glucagon (R = 0.782; P = .008), but not with changes in glucose, insulin, intact glucagon‐like peptide‐1, renin or FENa. Change in glucagon was associated with change in RE (R = 0.830; P = .003). Conclusions In contrast to our hypothesis, compared with glimepiride, linagliptin does not reduce postprandial hyperfiltration, yet appears to increase FF after meal ingestion by increasing blood pressure or RE.</description><subject>Adult</subject><subject>Blood Glucose</subject><subject>Blood pressure</subject><subject>Body weight</subject><subject>Clinical trials</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2</subject><subject>dipeptidyl peptidase‐4</subject><subject>Dipeptidyl-peptidase IV</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - therapeutic use</subject><subject>Dipeptidyl-Peptidases and Tripeptidyl-Peptidases</subject><subject>Double-Blind Method</subject><subject>Double-blind studies</subject><subject>DPP‐4 inhibitor</subject><subject>Glomerular filtration rate</subject><subject>Glucagon</subject><subject>Glycated Hemoglobin A</subject><subject>Hemodynamics</subject><subject>Humans</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Inhibitor drugs</subject><subject>Insulin</subject><subject>linagliptin</subject><subject>Linagliptin - therapeutic use</subject><subject>Meals</subject><subject>Metformin</subject><subject>Original</subject><subject>Overweight</subject><subject>Peptidase</subject><subject>postrandial hyperfiltration</subject><subject>Renin</subject><subject>Sulfonylurea Compounds</subject><subject>sulphonylurea</subject><subject>Treatment Outcome</subject><subject>type 2 diabetes</subject><subject>Vasoactive agents</subject><issn>1462-8902</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp1kstu1DAUhi0EomVgwQsgS2xaiWmT2I4TFkijUqDSQBGXdeTYJ40rxw620yqseASekRWPgWemVICEF77ofOf3f-yD0OM8O8rTOFZuOMopY_wO2s9pSZY5Kcq7232xrOqs2EMPQrjMsoySit9He4SyKqs520c_37sQRy-s0sJgDzbNvYDBqdmKQUsMXQcyBuw6HHvASo8wRq1mg3cbEeDHt-8Ua9vrVkfnsdFWXBidghZfgQ9T2GaGyYy9s7OZPAicgAFG7bWClIqFmky65FrHHsd5BFykm0QLEQI--HD6brU--3j4HK_w6EFBpy2oJNiGOKl5Y03gTQlu0F9BPcPKTa3Z2GqTF4WjT7U9RPc6YQI8ulkX6POr008nb5br89dnJ6v1UlJK-LKUpZSkFLkqCbBSMgY0I1SoXLWcKKaySlVdLVk6yKpjwCvOcxAdV21RtBlZoBc73XFqB1ASbPTCNKPXg_Bz44Ru_o5Y3TcX7qqpi5qQJLtABzcC3n2ZIMRm0EGCMcKCm0JTMM4pIzUpE_r0H_TSTT59YaLKjNe0ounHF-hwR0nvQvDQ3ZrJs2bTP016uGbbP4l98qf7W_J3wyTgeAdcawPz_5Wal-dvd5K_ANad2CY</recordid><startdate>202201</startdate><enddate>202201</enddate><creator>Muskiet, Marcel H. A.</creator><creator>Tonneijck, Lennart</creator><creator>Smits, Mark M.</creator><creator>Kramer, Mark H. H.</creator><creator>Ouwens, D. Margriet</creator><creator>Hartmann, Bolette</creator><creator>Holst, Jens J.</creator><creator>Danser, A. H. Jan</creator><creator>Joles, Jaap A.</creator><creator>Raalte, Daniël H.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><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><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8236-8842</orcidid><orcidid>https://orcid.org/0000-0003-4116-555X</orcidid><orcidid>https://orcid.org/0000-0001-5637-910X</orcidid></search><sort><creationdate>202201</creationdate><title>Postprandial renal haemodynamic effects of the dipeptidyl peptidase‐4 inhibitor linagliptin versus the sulphonylurea glimepiride in adults with type 2 diabetes (RENALIS): A predefined substudy of a randomized, double‐blind trial</title><author>Muskiet, Marcel H. A. ; Tonneijck, Lennart ; Smits, Mark M. ; Kramer, Mark H. H. ; Ouwens, D. Margriet ; Hartmann, Bolette ; Holst, Jens J. ; Danser, A. H. 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A.</creatorcontrib><creatorcontrib>Tonneijck, Lennart</creatorcontrib><creatorcontrib>Smits, Mark M.</creatorcontrib><creatorcontrib>Kramer, Mark H. H.</creatorcontrib><creatorcontrib>Ouwens, D. Margriet</creatorcontrib><creatorcontrib>Hartmann, Bolette</creatorcontrib><creatorcontrib>Holst, Jens J.</creatorcontrib><creatorcontrib>Danser, A. H. 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A.</au><au>Tonneijck, Lennart</au><au>Smits, Mark M.</au><au>Kramer, Mark H. H.</au><au>Ouwens, D. Margriet</au><au>Hartmann, Bolette</au><au>Holst, Jens J.</au><au>Danser, A. H. Jan</au><au>Joles, Jaap A.</au><au>Raalte, Daniël H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Postprandial renal haemodynamic effects of the dipeptidyl peptidase‐4 inhibitor linagliptin versus the sulphonylurea glimepiride in adults with type 2 diabetes (RENALIS): A predefined substudy of a randomized, double‐blind trial</atitle><jtitle>Diabetes, obesity &amp; metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2022-01</date><risdate>2022</risdate><volume>24</volume><issue>1</issue><spage>115</spage><epage>124</epage><pages>115-124</pages><issn>1462-8902</issn><eissn>1463-1326</eissn><abstract>Aim To determine the effect of the dipeptidyl peptidase‐4 inhibitor linagliptin on postprandial glomerular hyperfiltration compared with the sulphonylurea glimepiride in adults with type 2 diabetes (T2D). Materials and Methods In this predefined substudy within a randomized, double‐blind, parallel‐group, intervention trial, overweight people with T2D without renal impairment were treated with once‐daily linagliptin 5 mg (N = 10) or glimepiride 1 mg (N = 13) as an add‐on to metformin for 8 weeks. After a standardized liquid protein‐rich meal, the glomerular filtration rate (GFR) and effective renal plasma flow were determined by inulin and para‐aminohippuric acid clearance, respectively, based on timed urine sampling. Intrarenal haemodynamics were estimated using the Gomez equations. Glucoregulatory/vasoactive hormones, urinary pH and fractional excretions (FE) of sodium, potassium and urea were measured. Results Compared with glimepiride, linagliptin increased the postprandial filtration fraction (FF; mean difference 2.1%‐point; P = .016) and estimated glomerular hydraulic pressure (mean difference 3.0 mmHg; P = .050), and tended to increase GFR (P = .08) and estimated efferent renal arteriolar resistance (RE; P = .08) from baseline to week 8. No differences in FE were noted. Glimepiride reduced HbA1c more than linagliptin (mean difference −0.40%; P = .004), without between‐group differences in time‐averaged postprandial glucose levels. In the linagliptin group, change in FF correlated with change in mean arterial pressure (R = 0.807; P = .009) and time‐averaged mean glucagon (R = 0.782; P = .008), but not with changes in glucose, insulin, intact glucagon‐like peptide‐1, renin or FENa. Change in glucagon was associated with change in RE (R = 0.830; P = .003). Conclusions In contrast to our hypothesis, compared with glimepiride, linagliptin does not reduce postprandial hyperfiltration, yet appears to increase FF after meal ingestion by increasing blood pressure or RE.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>34580975</pmid><doi>10.1111/dom.14557</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-8236-8842</orcidid><orcidid>https://orcid.org/0000-0003-4116-555X</orcidid><orcidid>https://orcid.org/0000-0001-5637-910X</orcidid><oa>free_for_read</oa></addata></record>
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ispartof Diabetes, obesity & metabolism, 2022-01, Vol.24 (1), p.115-124
issn 1462-8902
1463-1326
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9293357
source MEDLINE; Wiley Journals
subjects Adult
Blood Glucose
Blood pressure
Body weight
Clinical trials
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2
dipeptidyl peptidase‐4
Dipeptidyl-peptidase IV
Dipeptidyl-Peptidase IV Inhibitors - therapeutic use
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Double-Blind Method
Double-blind studies
DPP‐4 inhibitor
Glomerular filtration rate
Glucagon
Glycated Hemoglobin A
Hemodynamics
Humans
Hypoglycemic Agents - therapeutic use
Inhibitor drugs
Insulin
linagliptin
Linagliptin - therapeutic use
Meals
Metformin
Original
Overweight
Peptidase
postrandial hyperfiltration
Renin
Sulfonylurea Compounds
sulphonylurea
Treatment Outcome
type 2 diabetes
Vasoactive agents
title Postprandial renal haemodynamic effects of the dipeptidyl peptidase‐4 inhibitor linagliptin versus the sulphonylurea glimepiride in adults with type 2 diabetes (RENALIS): A predefined substudy of a randomized, double‐blind trial
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