Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study
Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones ("GOP"), mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GO...
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| Veröffentlicht in: | Diabetes care 2019-08, Vol.42 (8), p.1446-1453 |
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| creator | Behary, Preeshila Tharakan, George Alexiadou, Kleopatra Johnson, Nicholas Wewer Albrechtsen, Nicolai J Kenkre, Julia Cuenco, Joyceline Hope, David Anyiam, Oluwaseun Choudhury, Sirazum Alessimii, Haya Poddar, Ankur Minnion, James Doyle, Chedie Frost, Gary Le Roux, Carel Purkayastha, Sanjay Moorthy, Krishna Dhillo, Waljit Holst, Jens J Ahmed, Ahmed R Prevost, A Toby Bloom, Stephen R Tan, Tricia M |
| description | Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones ("GOP"), mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GOP on glycemia and body weight when given for 4 weeks to patients with diabetes and obesity.
In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (
= 15) or saline (
= 11) infusion for 4 weeks. We also studied 21 patients who had undergone RYGB and 22 patients who followed a very low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were
) body weight,
) fructosamine levels,
) glucose and insulin during a mixed meal test (MMT),
) energy expenditure (EE),
) energy intake (EI), and
) mean glucose and measures of glucose variability during continuous glucose monitoring.
GOP infusion was well tolerated over the 4-week period. There was a greater weight loss (
= 0.025) with GOP (mean change -4.4 [95% CI -5.3, -3.5] kg) versus saline (-2.5 [-4.1, -0.9] kg). GOP led to a greater improvement (
= 0.0026) in fructosamine (-44.1 [-62.7, -25.5] µmol/L) versus saline (-11.7 [-18.9, -4.5] µmol/L). Despite a smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose tolerance after a mixed-meal stimulus and reduced glycemic variability compared with RYGB and VLCD.
GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight. |
| doi_str_mv | 10.2337/dc19-0449 |
| format | Article |
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In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (
= 15) or saline (
= 11) infusion for 4 weeks. We also studied 21 patients who had undergone RYGB and 22 patients who followed a very low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were
) body weight,
) fructosamine levels,
) glucose and insulin during a mixed meal test (MMT),
) energy expenditure (EE),
) energy intake (EI), and
) mean glucose and measures of glucose variability during continuous glucose monitoring.
GOP infusion was well tolerated over the 4-week period. There was a greater weight loss (
= 0.025) with GOP (mean change -4.4 [95% CI -5.3, -3.5] kg) versus saline (-2.5 [-4.1, -0.9] kg). GOP led to a greater improvement (
= 0.0026) in fructosamine (-44.1 [-62.7, -25.5] µmol/L) versus saline (-11.7 [-18.9, -4.5] µmol/L). Despite a smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose tolerance after a mixed-meal stimulus and reduced glycemic variability compared with RYGB and VLCD.
GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight.</description><identifier>ISSN: 0149-5992</identifier><identifier>EISSN: 1935-5548</identifier><identifier>DOI: 10.2337/dc19-0449</identifier><identifier>PMID: 31177183</identifier><language>eng</language><publisher>United States: American Diabetes Association</publisher><subject>Adult ; Blood glucose ; Blood Glucose - drug effects ; Blood Glucose Self-Monitoring ; Body weight ; Body Weight - drug effects ; Body weight loss ; Comparators ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - drug therapy ; Drug Therapy, Combination ; Energy expenditure ; Energy intake ; Female ; Gastric bypass ; Glucagon ; Glucagon-like peptide 1 ; Glucagon-Like Peptide 1 - administration & dosage ; Glucose ; Glucose monitoring ; Glucose tolerance ; Hormones ; Humans ; Hypocaloric diet ; Hypoglycemia - blood ; Hypoglycemia - drug therapy ; Infusions, Subcutaneous ; Insulin ; Insulin - blood ; Male ; Meals ; Middle Aged ; Mimicry ; Nutrient deficiency ; Obesity ; Obesity - blood ; Obesity - drug therapy ; Oxyntomodulin - administration & dosage ; Peptide YY - administration & dosage ; Peptides ; Postprandial Period - drug effects ; Prediabetic State - blood ; Prediabetic State - drug therapy ; Randomization ; Research design ; Secretion ; Single-Blind Method ; Variability ; Weight control ; Weight Loss ; Weight reduction</subject><ispartof>Diabetes care, 2019-08, Vol.42 (8), p.1446-1453</ispartof><rights>2019 by the American Diabetes Association.</rights><rights>Copyright American Diabetes Association Aug 1, 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c348t-f0c327b01efb24c389f5b31683fc7b08fc3070635398bbc8a61e75998473a8af3</citedby><cites>FETCH-LOGICAL-c348t-f0c327b01efb24c389f5b31683fc7b08fc3070635398bbc8a61e75998473a8af3</cites><orcidid>0000-0001-6853-3805 ; 0000-0001-5873-3432 ; 0000-0001-5950-4316</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31177183$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Behary, Preeshila</creatorcontrib><creatorcontrib>Tharakan, George</creatorcontrib><creatorcontrib>Alexiadou, Kleopatra</creatorcontrib><creatorcontrib>Johnson, Nicholas</creatorcontrib><creatorcontrib>Wewer Albrechtsen, Nicolai J</creatorcontrib><creatorcontrib>Kenkre, Julia</creatorcontrib><creatorcontrib>Cuenco, Joyceline</creatorcontrib><creatorcontrib>Hope, David</creatorcontrib><creatorcontrib>Anyiam, Oluwaseun</creatorcontrib><creatorcontrib>Choudhury, Sirazum</creatorcontrib><creatorcontrib>Alessimii, Haya</creatorcontrib><creatorcontrib>Poddar, Ankur</creatorcontrib><creatorcontrib>Minnion, James</creatorcontrib><creatorcontrib>Doyle, Chedie</creatorcontrib><creatorcontrib>Frost, Gary</creatorcontrib><creatorcontrib>Le Roux, Carel</creatorcontrib><creatorcontrib>Purkayastha, Sanjay</creatorcontrib><creatorcontrib>Moorthy, Krishna</creatorcontrib><creatorcontrib>Dhillo, Waljit</creatorcontrib><creatorcontrib>Holst, Jens J</creatorcontrib><creatorcontrib>Ahmed, Ahmed R</creatorcontrib><creatorcontrib>Prevost, A Toby</creatorcontrib><creatorcontrib>Bloom, Stephen R</creatorcontrib><creatorcontrib>Tan, Tricia M</creatorcontrib><title>Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study</title><title>Diabetes care</title><addtitle>Diabetes Care</addtitle><description>Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones ("GOP"), mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GOP on glycemia and body weight when given for 4 weeks to patients with diabetes and obesity.
In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (
= 15) or saline (
= 11) infusion for 4 weeks. We also studied 21 patients who had undergone RYGB and 22 patients who followed a very low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were
) body weight,
) fructosamine levels,
) glucose and insulin during a mixed meal test (MMT),
) energy expenditure (EE),
) energy intake (EI), and
) mean glucose and measures of glucose variability during continuous glucose monitoring.
GOP infusion was well tolerated over the 4-week period. There was a greater weight loss (
= 0.025) with GOP (mean change -4.4 [95% CI -5.3, -3.5] kg) versus saline (-2.5 [-4.1, -0.9] kg). GOP led to a greater improvement (
= 0.0026) in fructosamine (-44.1 [-62.7, -25.5] µmol/L) versus saline (-11.7 [-18.9, -4.5] µmol/L). Despite a smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose tolerance after a mixed-meal stimulus and reduced glycemic variability compared with RYGB and VLCD.
GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight.</description><subject>Adult</subject><subject>Blood glucose</subject><subject>Blood Glucose - drug effects</subject><subject>Blood Glucose Self-Monitoring</subject><subject>Body weight</subject><subject>Body Weight - drug effects</subject><subject>Body weight loss</subject><subject>Comparators</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 - drug therapy</subject><subject>Drug Therapy, Combination</subject><subject>Energy expenditure</subject><subject>Energy intake</subject><subject>Female</subject><subject>Gastric bypass</subject><subject>Glucagon</subject><subject>Glucagon-like peptide 1</subject><subject>Glucagon-Like Peptide 1 - administration & dosage</subject><subject>Glucose</subject><subject>Glucose monitoring</subject><subject>Glucose tolerance</subject><subject>Hormones</subject><subject>Humans</subject><subject>Hypocaloric diet</subject><subject>Hypoglycemia - blood</subject><subject>Hypoglycemia - drug therapy</subject><subject>Infusions, Subcutaneous</subject><subject>Insulin</subject><subject>Insulin - blood</subject><subject>Male</subject><subject>Meals</subject><subject>Middle Aged</subject><subject>Mimicry</subject><subject>Nutrient deficiency</subject><subject>Obesity</subject><subject>Obesity - blood</subject><subject>Obesity - drug therapy</subject><subject>Oxyntomodulin - administration & dosage</subject><subject>Peptide YY - administration & dosage</subject><subject>Peptides</subject><subject>Postprandial Period - drug effects</subject><subject>Prediabetic State - blood</subject><subject>Prediabetic State - drug therapy</subject><subject>Randomization</subject><subject>Research design</subject><subject>Secretion</subject><subject>Single-Blind Method</subject><subject>Variability</subject><subject>Weight control</subject><subject>Weight Loss</subject><subject>Weight reduction</subject><issn>0149-5992</issn><issn>1935-5548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1vEzEQhi0EomnhwB9AlriAlKX2ej9sbm0oaaVIiWgR6mnlj9niatcOa2_F9mfxC3FIyoHTaEbPzLwzL0JvKPmYM1afGk1FRopCPEMzKliZlWXBn6MZoYXISiHyI3Qcwj0hieH8JTpilNY15WyGfi98r6wDg5erTUbneP1rctH33oyddXMsncEb2EZrAN_e4qt-O_gHCPjcmwl_B3v3I_5llt2kobcSW4fXCoKN0753AGOlggjh9GbaAs7x50P-CZ_hr4nxvX0EM8fX1t11kJ2nvWaXbzqpQfls4V0cfNcljddxNNMr9KKVXYDXh3iCvn25uFlcZqv18mpxtso0K3jMWqJZXitCoVV5oRkXbakYrThrdSrzVjNSk4qVTHClNJcVhTo9ixc1k1y27AS9389NJ_8cIcSmt0FD10kHfgxNnr5YFVVelgl99x9678fBJXVNnteMclGKIlEf9pQefAgDtM12sL0cpoaSZmdkszOy2RmZ2LeHiaPqwfwjn5xjfwCksJe8</recordid><startdate>201908</startdate><enddate>201908</enddate><creator>Behary, Preeshila</creator><creator>Tharakan, George</creator><creator>Alexiadou, Kleopatra</creator><creator>Johnson, Nicholas</creator><creator>Wewer Albrechtsen, Nicolai J</creator><creator>Kenkre, Julia</creator><creator>Cuenco, Joyceline</creator><creator>Hope, David</creator><creator>Anyiam, Oluwaseun</creator><creator>Choudhury, Sirazum</creator><creator>Alessimii, Haya</creator><creator>Poddar, Ankur</creator><creator>Minnion, James</creator><creator>Doyle, Chedie</creator><creator>Frost, Gary</creator><creator>Le Roux, Carel</creator><creator>Purkayastha, Sanjay</creator><creator>Moorthy, Krishna</creator><creator>Dhillo, Waljit</creator><creator>Holst, Jens J</creator><creator>Ahmed, Ahmed R</creator><creator>Prevost, A Toby</creator><creator>Bloom, Stephen R</creator><creator>Tan, Tricia M</creator><general>American Diabetes Association</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>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6853-3805</orcidid><orcidid>https://orcid.org/0000-0001-5873-3432</orcidid><orcidid>https://orcid.org/0000-0001-5950-4316</orcidid></search><sort><creationdate>201908</creationdate><title>Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study</title><author>Behary, Preeshila ; Tharakan, George ; Alexiadou, Kleopatra ; Johnson, Nicholas ; Wewer Albrechtsen, Nicolai J ; Kenkre, Julia ; Cuenco, Joyceline ; Hope, David ; Anyiam, Oluwaseun ; Choudhury, Sirazum ; Alessimii, Haya ; Poddar, Ankur ; Minnion, James ; Doyle, Chedie ; Frost, Gary ; Le Roux, Carel ; Purkayastha, Sanjay ; Moorthy, Krishna ; Dhillo, Waljit ; Holst, Jens J ; Ahmed, Ahmed R ; Prevost, A Toby ; Bloom, Stephen R ; Tan, Tricia M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c348t-f0c327b01efb24c389f5b31683fc7b08fc3070635398bbc8a61e75998473a8af3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Blood glucose</topic><topic>Blood Glucose - 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Academic</collection><jtitle>Diabetes care</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Behary, Preeshila</au><au>Tharakan, George</au><au>Alexiadou, Kleopatra</au><au>Johnson, Nicholas</au><au>Wewer Albrechtsen, Nicolai J</au><au>Kenkre, Julia</au><au>Cuenco, Joyceline</au><au>Hope, David</au><au>Anyiam, Oluwaseun</au><au>Choudhury, Sirazum</au><au>Alessimii, Haya</au><au>Poddar, Ankur</au><au>Minnion, James</au><au>Doyle, Chedie</au><au>Frost, Gary</au><au>Le Roux, Carel</au><au>Purkayastha, Sanjay</au><au>Moorthy, Krishna</au><au>Dhillo, Waljit</au><au>Holst, Jens J</au><au>Ahmed, Ahmed R</au><au>Prevost, A Toby</au><au>Bloom, Stephen R</au><au>Tan, Tricia M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study</atitle><jtitle>Diabetes care</jtitle><addtitle>Diabetes Care</addtitle><date>2019-08</date><risdate>2019</risdate><volume>42</volume><issue>8</issue><spage>1446</spage><epage>1453</epage><pages>1446-1453</pages><issn>0149-5992</issn><eissn>1935-5548</eissn><abstract>Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones ("GOP"), mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GOP on glycemia and body weight when given for 4 weeks to patients with diabetes and obesity.
In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (
= 15) or saline (
= 11) infusion for 4 weeks. We also studied 21 patients who had undergone RYGB and 22 patients who followed a very low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were
) body weight,
) fructosamine levels,
) glucose and insulin during a mixed meal test (MMT),
) energy expenditure (EE),
) energy intake (EI), and
) mean glucose and measures of glucose variability during continuous glucose monitoring.
GOP infusion was well tolerated over the 4-week period. There was a greater weight loss (
= 0.025) with GOP (mean change -4.4 [95% CI -5.3, -3.5] kg) versus saline (-2.5 [-4.1, -0.9] kg). GOP led to a greater improvement (
= 0.0026) in fructosamine (-44.1 [-62.7, -25.5] µmol/L) versus saline (-11.7 [-18.9, -4.5] µmol/L). Despite a smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose tolerance after a mixed-meal stimulus and reduced glycemic variability compared with RYGB and VLCD.
GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight.</abstract><cop>United States</cop><pub>American Diabetes Association</pub><pmid>31177183</pmid><doi>10.2337/dc19-0449</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-6853-3805</orcidid><orcidid>https://orcid.org/0000-0001-5873-3432</orcidid><orcidid>https://orcid.org/0000-0001-5950-4316</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0149-5992 |
| ispartof | Diabetes care, 2019-08, Vol.42 (8), p.1446-1453 |
| issn | 0149-5992 1935-5548 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2311646255 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adult Blood glucose Blood Glucose - drug effects Blood Glucose Self-Monitoring Body weight Body Weight - drug effects Body weight loss Comparators Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - drug therapy Drug Therapy, Combination Energy expenditure Energy intake Female Gastric bypass Glucagon Glucagon-like peptide 1 Glucagon-Like Peptide 1 - administration & dosage Glucose Glucose monitoring Glucose tolerance Hormones Humans Hypocaloric diet Hypoglycemia - blood Hypoglycemia - drug therapy Infusions, Subcutaneous Insulin Insulin - blood Male Meals Middle Aged Mimicry Nutrient deficiency Obesity Obesity - blood Obesity - drug therapy Oxyntomodulin - administration & dosage Peptide YY - administration & dosage Peptides Postprandial Period - drug effects Prediabetic State - blood Prediabetic State - drug therapy Randomization Research design Secretion Single-Blind Method Variability Weight control Weight Loss Weight reduction |
| title | Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T12%3A42%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Combined%20GLP-1,%20Oxyntomodulin,%20and%20Peptide%20YY%20Improves%20Body%20Weight%20and%20Glycemia%20in%20Obesity%20and%20Prediabetes/Type%202%20Diabetes:%20A%20Randomized,%20Single-Blinded,%20Placebo-Controlled%20Study&rft.jtitle=Diabetes%20care&rft.au=Behary,%20Preeshila&rft.date=2019-08&rft.volume=42&rft.issue=8&rft.spage=1446&rft.epage=1453&rft.pages=1446-1453&rft.issn=0149-5992&rft.eissn=1935-5548&rft_id=info:doi/10.2337/dc19-0449&rft_dat=%3Cproquest_cross%3E2311646255%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2273189594&rft_id=info:pmid/31177183&rfr_iscdi=true |