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Marie Oertel Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany

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Christian G Ziegler Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany
Department of Internal Medicine III, University Hospital Carl Gustav Carus Dresden, Dresden, Germany

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Michael Kohlhaas Comprehensive Heart Failure Center, Würzburg, Germany

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Alexander Nickel Comprehensive Heart Failure Center, Würzburg, Germany

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Simon Kloock Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany

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Christoph Maack Comprehensive Heart Failure Center, Würzburg, Germany

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Vasco Sequeira Comprehensive Heart Failure Center, Würzburg, Germany

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Martin Fassnacht Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany

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Ulrich Dischinger Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of Würzburg, Würzburg, Germany
Comprehensive Heart Failure Center, Würzburg, Germany

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, 20 ). Long-acting GLP-1 receptor (GLP-1-R) agonists, e.g. semaglutide, are already in clinical use for the treatment of obesity. In adults with overweight or obesity and without diabetes mellitus, semaglutide leads to a mean weight loss of about 10

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Jeppe Skov Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark
Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark

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Jens Juul Holst Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark

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Jens Peter Gøtze Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark

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Jørgen Frøkiær Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark
Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark

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Jens Sandahl Christiansen Department of Endocrinology and Internal Medicine, Novo Nordisk A/S, NNF center for Basic Metabolic Research, Department of Clinical Biochemistry, Department of Clinical Physiology and Molecular Imaging, Department of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark

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Introduction Glucagon-like peptide-1 (GLP1) is a gut-derived incretin hormone with multiple actions in addition to control of glucose homeostasis (1) . Synthetic GLP1 receptor (GLP1R) agonists lower blood pressure in patients with type 2 diabetes

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Christine Rode Andreasen Steno Diabetes Center Copenhagen, Gentofte, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Andreas Andersen Steno Diabetes Center Copenhagen, Gentofte, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Filip Krag Knop Steno Diabetes Center Copenhagen, Gentofte, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Tina Vilsbøll Steno Diabetes Center Copenhagen, Gentofte, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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neurodegenerative disease models ( 6 ). Deduced from both preclinical and human studies, GLP-1 has extra-pancreatic effects in the gut, kidney, nervous system, heart and immune system ( Fig. 1 ) ( 2 ). Multiple GLP-1R agonists (GLP-1RAs) utilising the plasma glucose

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L Ahlkvist
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K Brown Department of Clinical Sciences, GlaxoSmithKline, Biomedical Center, C11, Lund University, SE 22184 Lund, Sweden

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B Ahrén
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groups. Acute effect of GPR119 activation in CD and HFD-fed mice To determine changes in intestinal GLP1 secretion in insulin resistance, a GPR119 agonist (GSK706A, 10 mg/kg) or vehicle was given orally before (−10 min) an oral liquid test meal to CD and

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Giuseppe Lisco Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare, Bari, Italy

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Anna De Tullio Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare, Bari, Italy

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Olga Disoteo Diabetology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

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Giuseppina Piazzolla Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare, Bari, Italy

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Edoardo Guastamacchia Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare, Bari, Italy

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Carlo Sabbà Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare, Bari, Italy

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Vincenzo De Geronimo Unit of Endocrinology, Policlinico Morgagni CCD, Catania, Italy

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Enrico Papini Department of Endocrinology and Metabolism, Regina Apostolorum Hospital, Rome, Italy

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Vincenzo Triggiani Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare, Bari, Italy

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Background Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have relevant antihyperglycemic effects and provide significant improvement on diabetes-related outcomes such as overweight and obesity, cardiovascular and renal impairment, and

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Svjatoslavs Kistkins Pauls Stradiņš Clinical University Hospital, Riga, Latvia

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Othmar Moser Division of Exercise Physiology and Metabolism, Institute of Sport Science, University of Bayreuth, Bayreuth, Germany

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Vitālijs Ankudovičs Pauls Stradiņš Clinical University Hospital, Riga, Latvia

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Dmitrijs Blizņuks Institute of Smart Computing Technologies, Riga Technical University, Riga, Latvia

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Timurs Mihailovs Institute of Smart Computing Technologies, Riga Technical University, Riga, Latvia

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Sergejs Lobanovs Pauls Stradiņš Clinical University Hospital, Riga, Latvia

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Harald Sourij Trials Unit for Interdisciplinary Metabolic Medicine, Division of Endocrinology and Diabetolgoy, Medical University of Graz, Graz, Austria

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Andreas F H Pfeiffer Department of Endocrinology and Metabolic Medicine, Campus Benjamin Franklin, Charité University Medicine, Hindenburgdamm, Berlin, Germany

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Valdis Pīrāgs Pauls Stradiņš Clinical University Hospital, Riga, Latvia
Faculty of Medicine, University of Latvia, Riga, Latvia

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insulin sensitivity and beta-cell function and subsequently glycaemic control. GLP-1 receptor agonists and dual hormone therapies have exhibited promising outcomes in those with T2D and obesity. Tirzepatide, a dual GLP-1 and GIP receptor agonist, has

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Lili Liu Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China

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Zhuo Shao Department of General Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, Shanghai, China

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Ying Xia Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China

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Jiabi Qin Department of Epidemiology & Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China

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Yang Xiao Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China

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Zhiguang Zhou Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China

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Zubing Mei Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China

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. Incretin-based drugs, including glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 (DPP-4) inhibitors, may offer an opportunity to avoid these side effects. Theoretically, GLP-1 RAs are structurally and functionally similar to

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M Jensterle Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia

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A Podbregar University Rehabilitation Institute Republic of Slovenia, Ljubljana, Slovenia

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K Goricar University of Ljubljana, Faculty of Medicine, Institute of Biochemistry, Pharmacogenetics Laboratory, Ljubljana, Slovenia

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N Gregoric Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia

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A Janez Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia

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not yet been addressed in a prospective clinical study. There was only one retrospective observational study reporting that adding long-acting GLP1 receptor agonist liraglutide to LSM, metformin and TRT boosted erectile function in obese men with type

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Zhenyu Liu Department of Clinical Medicine, Beijing Luhe Hospital, Capital Medical University, Tongzhou District, Beijing, China

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Huixi Kong Department of Clinical Medicine, Beijing Shijitan Hospital, Capital Medical University, Haidian District, Beijing, China

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Baoyu Zhang Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Tongzhou District, Beijing, China

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response to an acute acid load ( 36 ). Glucagon-like peptide-1 receptor agonists Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exert hypoglycemic effects by activating the GLP-1 receptor in a glucose concentration-dependent manner

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Signe Frøssing Department of Internal Medicine, Center of Endocrinology and Metabolism, Herlev Gentofte Hospital, Copenhagen, Denmark
Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark

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Malin Nylander Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
Department of Obstetrics & Gynecology, Herlev Gentofte Hospital, Copenhagen, Denmark

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Caroline Kistorp Department of Internal Medicine, Center of Endocrinology and Metabolism, Herlev Gentofte Hospital, Copenhagen, Denmark
Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark

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Sven O Skouby Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
Department of Obstetrics & Gynecology, Herlev Gentofte Hospital, Copenhagen, Denmark

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Jens Faber Department of Internal Medicine, Center of Endocrinology and Metabolism, Herlev Gentofte Hospital, Copenhagen, Denmark
Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark

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agonists (GLP-1RA) were developed for treatment of hyperglycemia in T2D, but have additionally weight-reducing effect and have proven effective in smaller studies in women with PCOS ( 19 ). The LEADER study in high-risk patients with T2D reported that the

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