{"id":"https://openalex.org/W4281787239","doi":"https://doi.org/10.2337/db22-723-p","title":"723-P: The Dual Glucagon and Glucagon-Like Peptide-1 Receptor (GCGR/GLP-1R) Agonist BI 4569Reduces Body Weight in Diet-Induced Obese Mice Based on Food Intake Reduction and an Increase in Energy Expenditure","display_name":"723-P: The Dual Glucagon and Glucagon-Like Peptide-1 Receptor (GCGR/GLP-1R) Agonist BI 4569Reduces Body Weight in Diet-Induced Obese Mice Based on Food Intake Reduction and an Increase in Energy Expenditure","publication_year":2022,"publication_date":"2022-05-31","ids":{"openalex":"https://openalex.org/W4281787239","doi":"https://doi.org/10.2337/db22-723-p"},"language":"en","primary_location":{"id":"doi:10.2337/db22-723-p","doi":"https://doi.org/10.2337/db22-723-p","is_oa":false,"landing_page_url":"https://doi.org/10.2337/db22-723-p","pdf_url":null,"source":{"id":"https://openalex.org/S129060628","display_name":"Diabetes","issn_l":"0012-1797","issn":["0012-1797","1939-327X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320274","host_organization_name":"American Diabetes Association","host_organization_lineage":["https://openalex.org/P4310320274"],"host_organization_lineage_names":["American Diabetes Association"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Diabetes","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5062628939","display_name":"TINA ZIMMERMANN","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"TINA ZIMMERMANN","raw_affiliation_strings":["Biberach, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biberach, Germany","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5087697528","display_name":"LEO THOMAS","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"LEO THOMAS","raw_affiliation_strings":["Biberach, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biberach, Germany","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010246793","display_name":"Tamara Baader-Pagler","orcid":"https://orcid.org/0000-0002-1672-8739","observed_orcids":["https://orcid.org/0000-0002-1672-8739"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"TAMARA BAADER-PAGLER","raw_affiliation_strings":["Biberach, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biberach, Germany","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5072124896","display_name":"PETER HAEBEL","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"PETER HAEBEL","raw_affiliation_strings":["Biberach, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biberach, Germany","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073073730","display_name":"Heike Neubauer","orcid":"https://orcid.org/0000-0001-8470-968X","observed_orcids":["https://orcid.org/0000-0001-8470-968X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"HEIKE NEUBAUER","raw_affiliation_strings":["Biberach, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biberach, Germany","institution_ids":[]}]},{"author_position":"middle","author":{"id":null,"display_name":"ERIC SIMON","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"ERIC SIMON","raw_affiliation_strings":["Biberach, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biberach, Germany","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5029019028","display_name":"Wolfgang Reindl","orcid":"https://orcid.org/0000-0002-6982-8506","observed_orcids":["https://orcid.org/0000-0002-6982-8506"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"WOLFGANG REINDL","raw_affiliation_strings":["Biberach, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biberach, Germany","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5048547230","display_name":"Besnik Bajrami","orcid":"https://orcid.org/0000-0002-3827-8150","observed_orcids":["https://orcid.org/0000-0002-3827-8150"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"BESNIK BAJRAMI","raw_affiliation_strings":["Biberach, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biberach, Germany","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5039588975","display_name":"Wolfgang Rist","orcid":"https://orcid.org/0000-0002-0626-3544","observed_orcids":["https://orcid.org/0000-0002-0626-3544"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"WOLFGANG RIST","raw_affiliation_strings":["Biberach, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biberach, Germany","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5031652160","display_name":"Ingo Uphues","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"INGO UPHUES","raw_affiliation_strings":["Biberach, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biberach, Germany","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5083460732","display_name":"Robert Augustin","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"ROBERT AUGUSTIN","raw_affiliation_strings":["Biberach, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biberach, Germany","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.1245,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":{"value":0.31807895,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":93},"biblio":{"volume":"71","issue":"Supplement_1","first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10489","display_name":"Regulation of Appetite and Obesity","score":0.7167999744415283,"subfield":{"id":"https://openalex.org/subfields/2807","display_name":"Endocrine and Autonomic Systems"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10489","display_name":"Regulation of Appetite and Obesity","score":0.7167999744415283,"subfield":{"id":"https://openalex.org/subfields/2807","display_name":"Endocrine and Autonomic Systems"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10401","display_name":"Diabetes Treatment and Management","score":0.20190000534057617,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T12539","display_name":"Pharmacology and Obesity Treatment","score":0.06759999692440033,"subfield":{"id":"https://openalex.org/subfields/2736","display_name":"Pharmacology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/glucagon-receptor-agonist","display_name":"glucagon receptor agonist","score":0.800000011920929},{"id":"https://openalex.org/keywords/glp-1-receptor-agonists","display_name":"GLP-1 receptor agonists","score":0.9620000123977661},{"id":"https://openalex.org/keywords/dual-receptor-agonist","display_name":"dual receptor agonist","score":0.8090000152587891},{"id":"https://openalex.org/keywords/diet-induced-obesity","display_name":"diet-induced obesity","score":0.8309999704360962},{"id":"https://openalex.org/keywords/weight-loss","display_name":"weight loss","score":0.8799999952316284},{"id":"https://openalex.org/keywords/food-consumption","display_name":"dietary intake","score":0.7250000238418579},{"id":"https://openalex.org/keywords/energy-expenditure","display_name":"energy expenditure","score":0.968999981880188},{"id":"https://openalex.org/keywords/gastric-emptying","display_name":"gastric emptying","score":0.8330000042915344},{"id":"https://openalex.org/keywords/glucose-stimulated-insulin-secretion","display_name":"glucose-stimulated insulin secretion","score":0.9160000085830688},{"id":"https://openalex.org/keywords/nicotinamide-n-methyltransferase","display_name":"nicotinamide N-methyltransferase","score":0.5270000100135803},{"id":"https://openalex.org/keywords/fgf21","display_name":"FGF21","score":0.7609999775886536},{"id":"https://openalex.org/keywords/liver-lipid-content","display_name":"liver lipids","score":0.6729999780654907},{"id":"https://openalex.org/keywords/non-alcoholic-steatohepatitis","display_name":"nonalcoholic steatohepatitis","score":0.6370000243186951}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6734780073165894},{"id":"https://openalex.org/C2778542361","wikidata":"https://www.wikidata.org/wiki/Q14904911","display_name":"Glucagon receptor","level":4,"score":0.6438369750976562},{"id":"https://openalex.org/C2776398474","wikidata":"https://www.wikidata.org/wiki/Q424611","display_name":"Glucagon-like peptide-1","level":4,"score":0.6241301894187927},{"id":"https://openalex.org/C2909862629","wikidata":"https://www.wikidata.org/wiki/Q27261089","display_name":"Semaglutide","level":5,"score":0.5996474623680115},{"id":"https://openalex.org/C2778938600","wikidata":"https://www.wikidata.org/wiki/Q389934","display_name":"Agonist","level":3,"score":0.5494621396064758},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.5338766574859619},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.5280997157096863},{"id":"https://openalex.org/C2778563252","wikidata":"https://www.wikidata.org/wiki/Q170617","display_name":"Glucagon","level":3,"score":0.45636340975761414},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.4150257408618927},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3941907286643982},{"id":"https://openalex.org/C15744967","wikidata":"https://www.wikidata.org/wiki/Q9418","display_name":"Psychology","level":0,"score":0.37472236156463623},{"id":"https://openalex.org/C2777180221","wikidata":"https://www.wikidata.org/wiki/Q3025883","display_name":"Type 2 diabetes","level":3,"score":0.3481145203113556},{"id":"https://openalex.org/C555293320","wikidata":"https://www.wikidata.org/wiki/Q12206","display_name":"Diabetes mellitus","level":2,"score":0.33364295959472656},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.16429948806762695},{"id":"https://openalex.org/C71315377","wikidata":"https://www.wikidata.org/wiki/Q11364","display_name":"Hormone","level":2,"score":0.14790204167366028},{"id":"https://openalex.org/C2781308992","wikidata":"https://www.wikidata.org/wiki/Q2526479","display_name":"Liraglutide","level":4,"score":0.131337970495224},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.06463390588760376}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.2337/db22-723-p","doi":"https://doi.org/10.2337/db22-723-p","is_oa":false,"landing_page_url":"https://doi.org/10.2337/db22-723-p","pdf_url":null,"source":{"id":"https://openalex.org/S129060628","display_name":"Diabetes","issn_l":"0012-1797","issn":["0012-1797","1939-327X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320274","host_organization_name":"American Diabetes Association","host_organization_lineage":["https://openalex.org/P4310320274"],"host_organization_lineage_names":["American Diabetes Association"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Diabetes","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9763000011444092,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4381376491","https://openalex.org/W4308387643","https://openalex.org/W2053470401","https://openalex.org/W4381734495","https://openalex.org/W4311822262","https://openalex.org/W4361190240","https://openalex.org/W2049082976","https://openalex.org/W4402771411","https://openalex.org/W4382393568","https://openalex.org/W3175013534"],"abstract_inverted_index":{"BI":[0,14,41,64,90,129,155,179,212,240,267],"4569":[1,15,42,65,91,130,156,180,213,241,268],"is":[2,30],"a":[3,17,54,182,194],"synthetic":[4],"peptide":[5],"optimized":[6],"to":[7,244],"simultaneously":[8],"engage":[9],"the":[10,44,132,235,258,262],"GCGR":[11,46,219],"and":[12,29,47,60,77,101,113,125,232,252,280],"GLP-1R.":[13],"contains":[16],"fatty":[18],"acid-based":[19],"half-life":[20],"extension":[21],"that":[22],"supports":[23],"once-weekly":[24],"subcutaneous":[25],"injection":[26,86],"in":[27,32,35,49,87,121,143,169,218,247,276],"humans,":[28],"currently":[31],"clinical":[33,274],"investigation":[34],"patients":[36,277],"with":[37,53,107,164,193,216,278],"obesity":[38,279],"or":[39],"NASH.":[40],"activates":[43],"human":[45,51,82],"GLP-1R":[48,144],"100%":[50],"plasma":[52,126,229],"potency":[55],"(EC50)":[56],"of":[57,110,137,154,176,198,211,239,261],"6.3":[58],"nM":[59],"1":[61],"nM,":[62],"respectively.":[63,116],"potently":[66],"increases":[67],"glucose-stimulated":[68],"insulin":[69,78],"secretion":[70,79],"from":[71,80],"mouse":[72],"islets":[73],"(EC50":[74],"5.7":[75],"nM)":[76],"perifused":[81],"islets.":[83],"On":[84],"single":[85],"lean":[88],"mice,":[89],"dose-dependently":[92],"reduced":[93],"food":[94],"intake":[95],"(FI)":[96],",":[97],"gastric":[98],"emptying":[99],"(GE)":[100],"improved":[102],"oral":[103],"glucose":[104],"tolerance":[105],"(oGTT)":[106],"an":[108,245],"ED50":[109],"90,":[111],"41,":[112],"2.1":[114],"nmol/kg,":[115,189],"Based":[117],"on":[118],"dose-dependent":[119],"changes":[120,217],"liver":[122,225],"NNMT":[123,227],"mRNA":[124],"amino":[127],"acids,":[128],"engages":[131],"GCGR,":[133],"unlike":[134],"semaglutide.":[135],"Receptor-specificity":[136],"target":[138,220],"engagement":[139,221],"was":[140,162,214,242],"further":[141],"shown":[142],"knockout":[145],"mice":[146],"(FI,":[147],"GE,":[148],"oGTT)":[149],".":[150,206,255],"The":[151],"bodyweight-lowering":[152,184,209,237],"efficacy":[153,185,210,238],"(3,":[157],"10,":[158],"20,":[159],"30":[160,188],"nmol/kg)":[161,168,254],"compared":[163,192],"semaglutide":[165,199],"(20,":[166],"100":[167,202],"diet-induced":[170],"obese":[171],"mice.":[172],"After":[173],"4":[174],"weeks":[175],"daily":[177],"dosing,":[178],"showed":[181],"superior":[183,236],"(32%":[186],"at":[187,201,251],"p\u22640.0vs.":[190,204],"vehicle)":[191,205],"maximally":[195],"effective":[196],"dose":[197],"(27%":[200],"nmol/kg;":[203],"This":[207],"greater":[208],"associated":[215,281],"biomarkers,":[222],"such":[223],"as":[224],"lipids,":[226],"mRNA,":[228],"glucagon,":[230],"FGF21,":[231],"cholesterol.":[233],"Mechanistically,":[234],"attributed":[243],"increase":[246],"energy":[248],"expenditure":[249],"(measured":[250],"20":[253],"In":[256],"summary,":[257],"preclinical":[259],"characterization":[260],"novel":[263],"dual":[264],"GCGR/GLP-1R":[265],"agonist":[266],"provides":[269],"strong":[270],"evidence":[271],"for":[272],"its":[273],"benefit":[275],"comorbidities.":[282],"Disclosure":[283],"T.":[284,298],"Zimmermann:":[285],"Employee;":[286,293,300,307,314,321,329,339,346],"Boehringer":[287,294,301,308,315,322,330,340,347],"Ingelheim":[288,295,302,309,316,323,331,341,348],"Pharma":[289,324],"GmbH&Co.KG.":[290],"L.":[291],"Thomas:":[292],"International":[296,303,310,317,332,342,349],"GmbH.":[297,304,311,318,333,343,350],"Baader-Pagler:":[299],"P.":[305],"Haebel:":[306],"H.":[312],"Neubauer:":[313],"E.":[319],"Simon:":[320],"GmbH&Co":[325],"KG.":[326],"W.":[327,337],"Reindl:":[328],"B.":[334],"Bajrami:":[335],"None.":[336,353],"Rist:":[338],"I.":[344],"Uphues:":[345],"R.":[351],"Augustin:":[352]},"counts_by_year":[{"year":2025,"cited_by_count":1}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2022-06-13T00:00:00"}
