Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial
Aims/hypothesis This study aimed to investigate the acute renal effects of the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide in type 2 diabetes patients. Methods We included overweight (BMI 25–40 kg/m 2 ) men and postmenopausal women, aged 35–75 years with type 2 diabetes (HbA 1c 48–7...
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| Veröffentlicht in: | Diabetologia 2016-07, Vol.59 (7), p.1412-1421 |
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| creator | Tonneijck, Lennart Smits, Mark M. Muskiet, Marcel H. A. Hoekstra, Trynke Kramer, Mark H. H. Danser, A. H. Jan Diamant, Michaela Joles, Jaap A. van Raalte, Daniël H. |
| description | Aims/hypothesis
This study aimed to investigate the acute renal effects of the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide in type 2 diabetes patients.
Methods
We included overweight (BMI 25–40 kg/m
2
) men and postmenopausal women, aged 35–75 years with type 2 diabetes (HbA
1c
48–75 mmol/mol; 6.5–9.0%) and estimated GFR ≥ 60 ml min
−1
1.73 m
−2
. Exenatide or placebo (NaCl solution, 154 mmol/l) was administrated intravenously in an acute, randomised, double-blind, placebo-controlled trial conducted at the Diabetes Center VU University Medical Center (VUMC). GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance, respectively, based on timed urine sampling. Filtration fraction (FF) and effective renal vascular resistance (ERVR) were calculated, and glomerular hydrostatic pressure (P
GLO
) and vascular resistance of the afferent (R
A
) and efferent (R
E
) renal arteriole were estimated. Tubular function was assessed by absolute and fractional excretion of sodium (FE
Na
), potassium (FE
K
) and urea (FE
U
), in addition to urine osmolality, pH and free water clearance. Renal damage markers, BP and plasma glucose were also determined.
Results
Of the 57 patients randomised by computer, 52 were included in the final analyses. Exenatide (
n
= 24) did not affect GFR (mean difference +2 ± 3 ml min
−1
1.73 m
−2
,
p
= 0.489), ERPF, FF, ERVR or P
GLO
, compared with placebo (
n
= 28). Exenatide increased R
A
(
p
|
| doi_str_mv | 10.1007/s00125-016-3938-z |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4901099</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4083697161</sourcerecordid><originalsourceid>FETCH-LOGICAL-c503t-f220b9bd9c0386c7b7b13a36d12cccef46803eeed4a93541e5747711d76671f43</originalsourceid><addsrcrecordid>eNqFkkFrFTEUhQdR7LP6A9xIwI0Lo7lJJjPjolCKVuGBLhTchUzmznspeZMxyVTbX-LPNY9XSxXEVQjnuyf3kFNVT4G9Asaa14kx4DVloKjoREuv71UrkIJTJnl7v1rtZQqt-npUPUrpgjEmaqkeVke8YaKVNayqn6d2yUgiTsYTHEe0OZEwkrxFcr7-RKFIFuccIjGbMLmUCf4ocHYDEjeRcInxO7rNNpN8NSPhZHCmx4yJzAXCKac3xJBopiHsXMLhJRnC0nukvXdTuc3eWOwDtWHKMXiPA8nRGf-4ejAan_DJzXlcfXn39vPZe7r-eP7h7HRNbc1EpiPnrO_6obMlkbJN3_QgjFADcGstjlK1TCDiIE1XwgPWjWwagKFRqoFRiuPq5OA7L_0OB1s2jsbrObqdiVc6GKf_VCa31ZtwqWXHgHVdMXhxYxDDtwVT1iWnRe_NhGFJGlrWKmi55P9Hm65uVQscCvr8L_QiLLF80oGSoga1N4QDZWNIKeJ4uzcwva-IPlREl4rofUX0dZl5djfw7cTvThSAH4BUpGmD8c7T_3T9BVPjyRk</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1795435162</pqid></control><display><type>article</type><title>Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Tonneijck, Lennart ; Smits, Mark M. ; Muskiet, Marcel H. A. ; Hoekstra, Trynke ; Kramer, Mark H. H. ; Danser, A. H. Jan ; Diamant, Michaela ; Joles, Jaap A. ; van Raalte, Daniël H.</creator><creatorcontrib>Tonneijck, Lennart ; Smits, Mark M. ; Muskiet, Marcel H. A. ; Hoekstra, Trynke ; Kramer, Mark H. H. ; Danser, A. H. Jan ; Diamant, Michaela ; Joles, Jaap A. ; van Raalte, Daniël H.</creatorcontrib><description>Aims/hypothesis
This study aimed to investigate the acute renal effects of the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide in type 2 diabetes patients.
Methods
We included overweight (BMI 25–40 kg/m
2
) men and postmenopausal women, aged 35–75 years with type 2 diabetes (HbA
1c
48–75 mmol/mol; 6.5–9.0%) and estimated GFR ≥ 60 ml min
−1
1.73 m
−2
. Exenatide or placebo (NaCl solution, 154 mmol/l) was administrated intravenously in an acute, randomised, double-blind, placebo-controlled trial conducted at the Diabetes Center VU University Medical Center (VUMC). GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance, respectively, based on timed urine sampling. Filtration fraction (FF) and effective renal vascular resistance (ERVR) were calculated, and glomerular hydrostatic pressure (P
GLO
) and vascular resistance of the afferent (R
A
) and efferent (R
E
) renal arteriole were estimated. Tubular function was assessed by absolute and fractional excretion of sodium (FE
Na
), potassium (FE
K
) and urea (FE
U
), in addition to urine osmolality, pH and free water clearance. Renal damage markers, BP and plasma glucose were also determined.
Results
Of the 57 patients randomised by computer, 52 were included in the final analyses. Exenatide (
n
= 24) did not affect GFR (mean difference +2 ± 3 ml min
−1
1.73 m
−2
,
p
= 0.489), ERPF, FF, ERVR or P
GLO
, compared with placebo (
n
= 28). Exenatide increased R
A
(
p
< 0.05), but did not change R
E
. Exenatide increased FE
Na
, FE
K
, urine osmolality and pH, while FE
U
, urinary flow and free water clearance were decreased (all
p
< 0.05). Osmolar clearance and renal damage makers were not affected. Diastolic BP and mean arterial pressure increased by 3 ± 1 and 6 ± 2 mmHg, respectively, whereas plasma glucose decreased by 1.4 ± 0.1 mmol/l (all
p
< 0.05).
Conclusions/interpretation
Exenatide infusion does not acutely affect renal haemodynamics in overweight type 2 diabetes patients at normal filtration levels. Furthermore, acute GLP-1RA administration increases proximal sodium excretion in these patients.
Trial registration
ClincialTrials.gov NCT01744236
Funding
The research leading to these results has been funded from: (1) the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 282521 – the SAFEGUARD project; and (2) the Dutch Kidney Foundation, under grant agreement IP12.87.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-016-3938-z</identifier><identifier>PMID: 27038451</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Aged ; Blood Pressure - drug effects ; Clinical trials ; Diabetes ; Diabetes Mellitus, Type 2 - drug therapy ; Double-Blind Method ; Female ; Glomerular Filtration Rate - drug effects ; Glucagon ; Glucagon-Like Peptide-1 Receptor - antagonists & inhibitors ; Glucose ; Hemodynamics ; Hemodynamics - drug effects ; Human Physiology ; Humans ; Hypoglycemic Agents - therapeutic use ; Internal Medicine ; Kidney - drug effects ; Kidney - metabolism ; Male ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Middle Aged ; Overweight ; Overweight - physiopathology ; Peptides ; Peptides - therapeutic use ; Placebo Effect ; Plasma ; Potassium ; Urine ; Venoms - therapeutic use</subject><ispartof>Diabetologia, 2016-07, Vol.59 (7), p.1412-1421</ispartof><rights>The Author(s) 2016</rights><rights>Springer-Verlag Berlin Heidelberg 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-f220b9bd9c0386c7b7b13a36d12cccef46803eeed4a93541e5747711d76671f43</citedby><cites>FETCH-LOGICAL-c503t-f220b9bd9c0386c7b7b13a36d12cccef46803eeed4a93541e5747711d76671f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-016-3938-z$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-016-3938-z$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27038451$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tonneijck, Lennart</creatorcontrib><creatorcontrib>Smits, Mark M.</creatorcontrib><creatorcontrib>Muskiet, Marcel H. A.</creatorcontrib><creatorcontrib>Hoekstra, Trynke</creatorcontrib><creatorcontrib>Kramer, Mark H. H.</creatorcontrib><creatorcontrib>Danser, A. H. Jan</creatorcontrib><creatorcontrib>Diamant, Michaela</creatorcontrib><creatorcontrib>Joles, Jaap A.</creatorcontrib><creatorcontrib>van Raalte, Daniël H.</creatorcontrib><title>Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
This study aimed to investigate the acute renal effects of the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide in type 2 diabetes patients.
Methods
We included overweight (BMI 25–40 kg/m
2
) men and postmenopausal women, aged 35–75 years with type 2 diabetes (HbA
1c
48–75 mmol/mol; 6.5–9.0%) and estimated GFR ≥ 60 ml min
−1
1.73 m
−2
. Exenatide or placebo (NaCl solution, 154 mmol/l) was administrated intravenously in an acute, randomised, double-blind, placebo-controlled trial conducted at the Diabetes Center VU University Medical Center (VUMC). GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance, respectively, based on timed urine sampling. Filtration fraction (FF) and effective renal vascular resistance (ERVR) were calculated, and glomerular hydrostatic pressure (P
GLO
) and vascular resistance of the afferent (R
A
) and efferent (R
E
) renal arteriole were estimated. Tubular function was assessed by absolute and fractional excretion of sodium (FE
Na
), potassium (FE
K
) and urea (FE
U
), in addition to urine osmolality, pH and free water clearance. Renal damage markers, BP and plasma glucose were also determined.
Results
Of the 57 patients randomised by computer, 52 were included in the final analyses. Exenatide (
n
= 24) did not affect GFR (mean difference +2 ± 3 ml min
−1
1.73 m
−2
,
p
= 0.489), ERPF, FF, ERVR or P
GLO
, compared with placebo (
n
= 28). Exenatide increased R
A
(
p
< 0.05), but did not change R
E
. Exenatide increased FE
Na
, FE
K
, urine osmolality and pH, while FE
U
, urinary flow and free water clearance were decreased (all
p
< 0.05). Osmolar clearance and renal damage makers were not affected. Diastolic BP and mean arterial pressure increased by 3 ± 1 and 6 ± 2 mmHg, respectively, whereas plasma glucose decreased by 1.4 ± 0.1 mmol/l (all
p
< 0.05).
Conclusions/interpretation
Exenatide infusion does not acutely affect renal haemodynamics in overweight type 2 diabetes patients at normal filtration levels. Furthermore, acute GLP-1RA administration increases proximal sodium excretion in these patients.
Trial registration
ClincialTrials.gov NCT01744236
Funding
The research leading to these results has been funded from: (1) the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 282521 – the SAFEGUARD project; and (2) the Dutch Kidney Foundation, under grant agreement IP12.87.</description><subject>Adult</subject><subject>Aged</subject><subject>Blood Pressure - drug effects</subject><subject>Clinical trials</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Glomerular Filtration Rate - drug effects</subject><subject>Glucagon</subject><subject>Glucagon-Like Peptide-1 Receptor - antagonists & inhibitors</subject><subject>Glucose</subject><subject>Hemodynamics</subject><subject>Hemodynamics - drug effects</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Internal Medicine</subject><subject>Kidney - drug effects</subject><subject>Kidney - metabolism</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Middle Aged</subject><subject>Overweight</subject><subject>Overweight - physiopathology</subject><subject>Peptides</subject><subject>Peptides - therapeutic use</subject><subject>Placebo Effect</subject><subject>Plasma</subject><subject>Potassium</subject><subject>Urine</subject><subject>Venoms - therapeutic use</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkkFrFTEUhQdR7LP6A9xIwI0Lo7lJJjPjolCKVuGBLhTchUzmznspeZMxyVTbX-LPNY9XSxXEVQjnuyf3kFNVT4G9Asaa14kx4DVloKjoREuv71UrkIJTJnl7v1rtZQqt-npUPUrpgjEmaqkeVke8YaKVNayqn6d2yUgiTsYTHEe0OZEwkrxFcr7-RKFIFuccIjGbMLmUCf4ocHYDEjeRcInxO7rNNpN8NSPhZHCmx4yJzAXCKac3xJBopiHsXMLhJRnC0nukvXdTuc3eWOwDtWHKMXiPA8nRGf-4ejAan_DJzXlcfXn39vPZe7r-eP7h7HRNbc1EpiPnrO_6obMlkbJN3_QgjFADcGstjlK1TCDiIE1XwgPWjWwagKFRqoFRiuPq5OA7L_0OB1s2jsbrObqdiVc6GKf_VCa31ZtwqWXHgHVdMXhxYxDDtwVT1iWnRe_NhGFJGlrWKmi55P9Hm65uVQscCvr8L_QiLLF80oGSoga1N4QDZWNIKeJ4uzcwva-IPlREl4rofUX0dZl5djfw7cTvThSAH4BUpGmD8c7T_3T9BVPjyRk</recordid><startdate>20160701</startdate><enddate>20160701</enddate><creator>Tonneijck, Lennart</creator><creator>Smits, Mark M.</creator><creator>Muskiet, Marcel H. A.</creator><creator>Hoekstra, Trynke</creator><creator>Kramer, Mark H. H.</creator><creator>Danser, A. H. Jan</creator><creator>Diamant, Michaela</creator><creator>Joles, Jaap A.</creator><creator>van Raalte, Daniël H.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160701</creationdate><title>Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial</title><author>Tonneijck, Lennart ; Smits, Mark M. ; Muskiet, Marcel H. A. ; Hoekstra, Trynke ; Kramer, Mark H. H. ; Danser, A. H. Jan ; Diamant, Michaela ; Joles, Jaap A. ; van Raalte, Daniël H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c503t-f220b9bd9c0386c7b7b13a36d12cccef46803eeed4a93541e5747711d76671f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Blood Pressure - drug effects</topic><topic>Clinical trials</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Glomerular Filtration Rate - drug effects</topic><topic>Glucagon</topic><topic>Glucagon-Like Peptide-1 Receptor - antagonists & inhibitors</topic><topic>Glucose</topic><topic>Hemodynamics</topic><topic>Hemodynamics - drug effects</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Internal Medicine</topic><topic>Kidney - drug effects</topic><topic>Kidney - metabolism</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Middle Aged</topic><topic>Overweight</topic><topic>Overweight - physiopathology</topic><topic>Peptides</topic><topic>Peptides - therapeutic use</topic><topic>Placebo Effect</topic><topic>Plasma</topic><topic>Potassium</topic><topic>Urine</topic><topic>Venoms - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tonneijck, Lennart</creatorcontrib><creatorcontrib>Smits, Mark M.</creatorcontrib><creatorcontrib>Muskiet, Marcel H. A.</creatorcontrib><creatorcontrib>Hoekstra, Trynke</creatorcontrib><creatorcontrib>Kramer, Mark H. H.</creatorcontrib><creatorcontrib>Danser, A. H. Jan</creatorcontrib><creatorcontrib>Diamant, Michaela</creatorcontrib><creatorcontrib>Joles, Jaap A.</creatorcontrib><creatorcontrib>van Raalte, Daniël H.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tonneijck, Lennart</au><au>Smits, Mark M.</au><au>Muskiet, Marcel H. A.</au><au>Hoekstra, Trynke</au><au>Kramer, Mark H. H.</au><au>Danser, A. H. Jan</au><au>Diamant, Michaela</au><au>Joles, Jaap A.</au><au>van Raalte, Daniël H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2016-07-01</date><risdate>2016</risdate><volume>59</volume><issue>7</issue><spage>1412</spage><epage>1421</epage><pages>1412-1421</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
This study aimed to investigate the acute renal effects of the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide in type 2 diabetes patients.
Methods
We included overweight (BMI 25–40 kg/m
2
) men and postmenopausal women, aged 35–75 years with type 2 diabetes (HbA
1c
48–75 mmol/mol; 6.5–9.0%) and estimated GFR ≥ 60 ml min
−1
1.73 m
−2
. Exenatide or placebo (NaCl solution, 154 mmol/l) was administrated intravenously in an acute, randomised, double-blind, placebo-controlled trial conducted at the Diabetes Center VU University Medical Center (VUMC). GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance, respectively, based on timed urine sampling. Filtration fraction (FF) and effective renal vascular resistance (ERVR) were calculated, and glomerular hydrostatic pressure (P
GLO
) and vascular resistance of the afferent (R
A
) and efferent (R
E
) renal arteriole were estimated. Tubular function was assessed by absolute and fractional excretion of sodium (FE
Na
), potassium (FE
K
) and urea (FE
U
), in addition to urine osmolality, pH and free water clearance. Renal damage markers, BP and plasma glucose were also determined.
Results
Of the 57 patients randomised by computer, 52 were included in the final analyses. Exenatide (
n
= 24) did not affect GFR (mean difference +2 ± 3 ml min
−1
1.73 m
−2
,
p
= 0.489), ERPF, FF, ERVR or P
GLO
, compared with placebo (
n
= 28). Exenatide increased R
A
(
p
< 0.05), but did not change R
E
. Exenatide increased FE
Na
, FE
K
, urine osmolality and pH, while FE
U
, urinary flow and free water clearance were decreased (all
p
< 0.05). Osmolar clearance and renal damage makers were not affected. Diastolic BP and mean arterial pressure increased by 3 ± 1 and 6 ± 2 mmHg, respectively, whereas plasma glucose decreased by 1.4 ± 0.1 mmol/l (all
p
< 0.05).
Conclusions/interpretation
Exenatide infusion does not acutely affect renal haemodynamics in overweight type 2 diabetes patients at normal filtration levels. Furthermore, acute GLP-1RA administration increases proximal sodium excretion in these patients.
Trial registration
ClincialTrials.gov NCT01744236
Funding
The research leading to these results has been funded from: (1) the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 282521 – the SAFEGUARD project; and (2) the Dutch Kidney Foundation, under grant agreement IP12.87.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>27038451</pmid><doi>10.1007/s00125-016-3938-z</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-186X |
| ispartof | Diabetologia, 2016-07, Vol.59 (7), p.1412-1421 |
| issn | 0012-186X 1432-0428 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4901099 |
| source | MEDLINE; SpringerNature Journals |
| subjects | Adult Aged Blood Pressure - drug effects Clinical trials Diabetes Diabetes Mellitus, Type 2 - drug therapy Double-Blind Method Female Glomerular Filtration Rate - drug effects Glucagon Glucagon-Like Peptide-1 Receptor - antagonists & inhibitors Glucose Hemodynamics Hemodynamics - drug effects Human Physiology Humans Hypoglycemic Agents - therapeutic use Internal Medicine Kidney - drug effects Kidney - metabolism Male Medicine Medicine & Public Health Metabolic Diseases Middle Aged Overweight Overweight - physiopathology Peptides Peptides - therapeutic use Placebo Effect Plasma Potassium Urine Venoms - therapeutic use |
| title | Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T10%3A48%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Acute%20renal%20effects%20of%20the%20GLP-1%20receptor%20agonist%20exenatide%20in%20overweight%20type%202%20diabetes%20patients:%20a%20randomised,%20double-blind,%20placebo-controlled%20trial&rft.jtitle=Diabetologia&rft.au=Tonneijck,%20Lennart&rft.date=2016-07-01&rft.volume=59&rft.issue=7&rft.spage=1412&rft.epage=1421&rft.pages=1412-1421&rft.issn=0012-186X&rft.eissn=1432-0428&rft_id=info:doi/10.1007/s00125-016-3938-z&rft_dat=%3Cproquest_pubme%3E4083697161%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1795435162&rft_id=info:pmid/27038451&rfr_iscdi=true |