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In this study we evaluated heterogeneity in body weight and glycaemic responses to the initiation of liraglutide, semaglutide or dulaglutide in real-world clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from 4467 adults with type 2 diabetes in the Diabetes Patient Follow-up (DPV) registry were analysed, focusing on changes in HbA\n                      <jats:sub>1c<\/jats:sub>\n                      and body weight over 6 months following initiation of a GLP-1 RA. We categorised participants based on their response: HbA\n                      <jats:sub>1c<\/jats:sub>\n                      reduction only, weight loss only, both or neither. This analysis was part of the IMI-Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (IMI-SOPHIA) project.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At 6 months\u2019 follow-up the median absolute HbA\n                      <jats:sub>1c<\/jats:sub>\n                      reduction was 5.3 mmol\/mol (IQR 13.9, \u22121.0) (0.49% [1.27, \u22120.09]) and relative body weight reduction was 1.43% (4.26, 0). Only 14% of participants achieved meaningful reductions in both HbA\n                      <jats:sub>1c<\/jats:sub>\n                      (absolute reduction \u22655.5 mmol\/mol [0.5%]) and body weight (relative reduction \u22655%). Men and those with a higher baseline HbA\n                      <jats:sub>1c<\/jats:sub>\n                      were more likely to show an HbA\n                      <jats:sub>1c<\/jats:sub>\n                      only response (36% of participants; both\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001), while older individuals and those with a longer diabetes duration were more likely to experience a weight-only response (7% of participants; both\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001). Higher baseline body weight and lower eGFR (both\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.05) correlated with greater weight reduction, whereas lower baseline HbA\n                      <jats:sub>1c<\/jats:sub>\n                      and longer diabetes duration were linked to smaller HbA\n                      <jats:sub>1c<\/jats:sub>\n                      reductions (both\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>\n                      There is significant heterogeneity in responses to GLP-1 RA therapy among individuals with type 2 diabetes in routine clinical practice. However, in our study a substantial proportion achieved a reduction in either body weight or HbA\n                      <jats:sub>1c<\/jats:sub>\n                      . Future studies should explore why some individuals achieve either weight loss or HbA\n                      <jats:sub>1c<\/jats:sub>\n                      reduction but not both.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-025-06448-w","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T15:01:42Z","timestamp":1747926102000},"page":"1666-1673","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Heterogeneity in response to GLP-1 receptor agonists in type 2 diabetes in real-world clinical practice: insights from the DPV register \u2013 an IMI-SOPHIA study"],"prefix":"10.1007","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8462-3832","authenticated-orcid":false,"given":"Martin","family":"Heni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Fr\u00fchwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram","family":"Karges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Naudorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Niem\u00f6ller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Pagnia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Reindel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Seufert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisa","family":"Ufer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard W.","family":"Holl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7570-9095","authenticated-orcid":false,"given":"Nicole","family":"Prinz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"issue":"10","key":"6448_CR1","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1007\/s00125-023-05956-x","volume":"66","author":"MA Nauck","year":"2023","unstructured":"Nauck MA, M\u00fcller TD (2023) Incretin hormones and type 2 diabetes. 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Hungele and R. Ranz for support and development of the DPV documentation software (both clinical data managers, Ulm University). The authors further wish to express their special gratitude to all DPV centres participating in the initiative. Centres contributing data to the present analysis were Aachen \u2013 Innere RWTH, Aidlingen Praxisgemeinschaft, Asbach Kamillus-Klinik Innere, Augsburg IV, Medizinische Uni-Klinik, Bad Aibling Internist, Praxis, Bad Aibling Internistische Praxis-2, Bad Oeynhausen Herz-und Diabeteszentrum NRW, Bad Reichenhall Kreisklinik Innere Medizin, Bayreuth Innere Medizin, Berchtesgaden CJD, Bergen Gemeinschaftspraxis, Berlin DRK-Kliniken Mitte Innere, Berlin Endokrinologikum, Berlin Klinik St. Hedwig Innere, Berlin Oskar Zieten Krankenhaus Innere, Berlin Schlosspark-Klinik Innere, Berlin Vivantes Hellersdorf Innere, Bodnegg \u2013 MVZ Wollmarsh\u00f6he, Bonn Schwerpunktpraxis, Bottrop Knappschaftskrankenhaus Innere, Bremen \u2013 Mitte Innere, Bremerhaven Kinderklinik, Castrop-Rauxel Rochus-Hospital, Chemnitz-Hartmannsdorf Innere Medizin \u2013 DIAKOMED-1, Coburg Innere Medizin, Coesfeld\/D\u00fclmen Innere Medizin, Darmstadt Innere Medizin, Deggendorf Gemeinschaftspraxis, Dortmund Johannes Hospital, Dortmund Knappschaftskrankenhaus Innere, Dortmund Medizinische Kliniken Nord, Dortmund-St. Josefshospital Innere, Dortmund-West Innere, Duisburg Homberg Helios Rhein-Ruhr Kliniken GmbH, Duisburg St. Anna Innere Helios Rhein-Ruhr Kliniken GmbH, Duisburg-Huckingen, Eckernf\u00f6rde Gemeinschaftspraxis, Eisleben Lutherstadt Helios-Klinik, Erlangen Uni Innere Medizin, Essen Diabetes-SPP, Essen Diabetes-Schwerpunktpraxis, Forchheim Diabeteszentrum SPP, Frankfurt Diabeteszentrum Rhein-Main-Erwachsenendiabetologie (B\u00fcrgerhospital), Frankfurt Uni-Klinik Innere, Frankfurt-Sachsenhausen Innere, Frankfurt-Sachsenhausen Innere MVZ, Freiburg Uni Innere, Geislingen Klinik Helfenstein Innere, Gie\u00dfen Evangelisches Krankenhaus Mittelhessen, G\u00f6ttingen Uni Gastroenterologie, G\u00fcstrow Innere, Halberstadt Innere Medizin AMEOS Klinik, Hanau diabetolologische Schwerpunktpraxis, Heide Westk\u00fcstenklinikum Innere Medizin, Heidelberg St. Josefskrankenhaus, Heidenheim Arztpraxis Allgemeinmedizin, Heilbronn Innere Klinik, Herford Innere Med I, Herne Evanangelisches Krankenhaus Innere, Hildesheim GmbH \u2013 Innere, Idar Oberstein Schwerpunktpraxis, Jena diabetologische Schwerpunktpraxis, Kamen Klinikum Westfalen Hellmig Krankenhaus, Kamen MKK \u2013 Medizinisches Kompetenzkollegium, Karlsburg Klinik f\u00fcr Diabetes und Stoffwechsel, Karlsruhe Schwerpunktpraxis, Kirchheim-N\u00fcrtingen Innere, Koblenz Kemperhof 1. Medizinische Klinik, Konstanz Innere Klinik, Krefeld-Uerdingen St. Josef Innere, Landau Innere, Lilienthal Diabeteszentrum, Limburg Innere Medizin, Lindlar DM-Zentrum, Linz Krankenhaus Barmherzige Schwestern Kardiologie Abt. Int. II, Ludwigshafen diabetol. SPP, Luxembourg \u2013 Centre Hospitalier, L\u00fcbeck Uni-Klinik Innere Medizin, L\u00fcnen Klinik am Park, Magdeburg St\u00e4dtisches Klinikum Innere, Manderscheid Rathauspraxis, Marktredwitz Innere Medizin, Memmingen Internistische Praxis, Murnau am Staffelsee \u2013 diabetol. SPP, M\u00fchlheim an der Ruhr Evang. Krankenhaus Medizinische Klinik, M\u00fcnchen Diabetes-Zentrum S\u00fcd, M\u00fcnchen Schwerpunktpraxis, M\u00fcnster Herz Jesu Innere, M\u00fcnster Ludgerus-Kliniken GmbH, Neunkirchen Innere Medizin, Neuwied Marienhaus Klinikum St. Elisabeth Innere, Oberndorf Gastroenterologische Praxis Schwerpunkt Diabetologie, Pirmasens St\u00e4dtisches Krankenhaus Innere, Prenzlau Krankenhaus Innere, Prien am Chiemsee Innere, Rosenheim Innere Medizin, Rosenheim Schwerpunktpraxis, Rottweil Gemeinschaftspraxis f\u00fcr Innere Medizin, Saaldorf-Surheim Diabetespraxis, Schwerin Innere Medizin, Spaichingen Innere, Stuttgart Sana Klinik Bethesda, Tettnang Innere Medizin, Traunstein diabetologische Schwerpunktpraxis, Trostberg Innere, Ulm Schwerpunktpraxis Bahnhofsplatz, Ulm Uni Innere Medizin, Ulm Uni-Kinderklinik, Viersen internist. Praxis, Villingen-Schwenningen Schwarzwald-Baar-Klinikum Innere, Wangen Oberschwabenklinik Innere Medizin, Weisswasser Kreiskrankenhaus, Wernberg-K\u00f6blitz SPP, Wien Uni Innere Medizin III, Wittlich DSP, Worms Schwerpunktpraxis.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"The data are not publicly available because they contain information that could compromise research participant privacy\/consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"Open Access funding enabled and organized by Projekt DEAL. The DPV initiative is funded by the German Center for Diabetes Research (DZD, grant no. 82DZD14E1G), the Robert Koch Institute (RKI, grant no. 1368-1711) and the German Diabetes Association (DDG). In addition, this study is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (SOPHIA) project (\n                      \n                      ). SOPHIA has received funding from the Innovative Medicines Initiative (IMI) 2 Joint Undertaking under grant agreement no. 875534. This Joint Undertaking receives support from the European Union\u2019s Horizon 2020 research and innovation program and EFPIA and the T1D Exchange, JDRF and Obesity Action Coalition. This article reflects the authors\u2019 views and neither the IMI nor the European Union, EFPIA or any associated partners are responsible for any use that may be made of the information contained therein.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Outside the current work, MH reports lecture fees from Chiesi\/Amryt, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk and Sanofi. He has also served on advisory boards for Chiesi\/Amryt, Boehringer Ingelheim and Sanofi. He is also currently a board member of the German Diabetes Association (DDG). Outside the current work, MN reports lecture fees from AstraZeneca and Dexcom. He is a member of the scientific committee of the Arbeitsgemeinschaft Diabetes & Technologie of the German Diabetes Association (DDG). Outside the current work, JR reports lecture fees from AstraZeneca and Sanofi. Outside the current work, JS has received honoraria for talks and\/or consultancy and\/or research funding from Apitope, AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Bristol-Meyers Squibb, Eli Lilly, GI Dynamics, GlaxoSmithKline, Intarcia, Ipsen, Janssen, LifeScan, MedScape, MSD, Novartis, Novo Nordisk, OmniaMed, Pfizer, Roche, Sanofi, Servier, Takeda and Ypsomed. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"MH and NP designed\/performed the analyses, discussed the findings and drafted the manuscript. LF, WK, MN, KN, FP, JR, JS, GU and CW were responsible for acquisition of the data and reviewed the manuscript critically for important intellectual content. RWH made substantial contributions to the initial conception of the work and reviewed the manuscript critically for important intellectual content. All authors approved the final version of the manuscript prior to submission. NP and RWH are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}