{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T13:50:15Z","timestamp":1782395415018,"version":"3.54.5"},"reference-count":90,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Semaglutide and tirzepatide demonstrate substantial efficacy in obesity treatment, yet individual responses vary markedly. The incretin system\u2014comprising glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)\u2014is frequently dysregulated in obesity, but whether fasting incretin levels predict differential pharmacological responses remains unexplored. We investigated whether combinatorial fasting GLP-1\/GIP tertile profiles predict the initial weight-loss response to semaglutide versus tirzepatide in patients with severe obesity. Methods: This prospective, parallel-group, open-label pilot study enrolled 90 treatment-na\u00efve patients with BMI &gt; 40 kg\/m2 (mean 42.5 \u00b1 3.5 kg\/m2) at the University of Catania, Italy. Fasting serum GLP-1 (0.8\u201350 pg\/mL) and GIP (1\u201316 ng\/mL) were measured by chemiluminescence immunoassay and distributed into tertiles, generating nine combinatorial profiles (P1\u2013P9; n = 10 per profile). Within each profile, five patients were randomly assigned to semaglutide (escalated to 2.4 mg\/week) or tirzepatide (escalated to 15 mg\/week). Primary outcome was pharmacological response category at six months: low (&lt;5% body weight reduction), intermediate (5\u201315%), or optimal (&gt;15%). Results: Baseline characteristics were balanced across profiles (age 48 \u00b1 8 years, BMI 42.5 \u00b1 3.5 kg\/m2, waist circumference 134 \u00b1 12 cm, HOMA-IR 8.5 \u00b1 3.0; all p &gt; 0.05). Tirzepatide achieved optimal response in profiles with low GIP tertile regardless of GLP-1 level (P1, P6, P8), while semaglutide achieved optimal response when GLP-1 was low and GIP was intermediate-to-high (P4, P5). Both drugs showed low response in the high GLP-1\/high GIP profile (P3). Mean weight loss in optimal-response groups was 18.2 \u00b1 2.1% for tirzepatide and 16.8 \u00b1 1.9% for semaglutide. Waist circumference reductions paralleled weight loss patterns. HOMA-IR decreased significantly in all optimal-response groups (mean reduction 4.2 \u00b1 1.1 units). Conclusions: In this hypothesis-generating pilot study, fasting GLP-1\/GIP combinatorial profiling, obtained from a single fasting blood sample, was associated with differential pharmacological responses to semaglutide and tirzepatide in severe obesity. Low GIP levels were tentatively associated with optimal tirzepatide response; low GLP-1 with intermediate-to-high GIP was tentatively associated with optimal semaglutide response. These preliminary findings provide proof-of-concept for incretin-guided personalised obesity pharmacotherapy but require confirmation in larger, adequately powered randomised trials before any clinical recommendations can be made. The inability to discriminate incretin secretory deficiency from receptor resistance using fasting measurements alone, the absence of a placebo control, and the six-month follow-up (shorter than the 12\u201318 months at which maximal efficacy is typically observed) remain critical limitations.<\/jats:p>","DOI":"10.3390\/diagnostics16131979","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T12:37:55Z","timestamp":1782391075000},"page":"1979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Do Fasting GLP-1 and GIP Levels Predict the Initial Pharmacological Response to Semaglutide and Tirzepatide?"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-2372","authenticated-orcid":false,"given":"Sandro","family":"La Vignera","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Fioriglio","sequence":"additional","affiliation":[{"name":"MEDISAN, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5217-9343","authenticated-orcid":false,"given":"Rosita A.","family":"Condorelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022, May 15). Obesity and Overweight. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41574-019-0176-8","article-title":"Obesity: Global epidemiology and pathogenesis","volume":"15","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.mcna.2017.08.012","article-title":"Maintenance of Lost Weight and Long-Term Management of Obesity","volume":"102","author":"Hall","year":"2018","journal-title":"Med. Clin. N. Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1017\/S0029665122002695","article-title":"A new era in gut hormone-based pharmacotherapy for people with obesity","volume":"81","author":"Firman","year":"2022","journal-title":"Proc. Nutr. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"206","DOI":"10.3803\/EnM.2024.1940","article-title":"Glucagon-Like Peptide-1 Based Therapies: A New Horizon in Obesity Management","volume":"39","author":"Son","year":"2024","journal-title":"Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"138","DOI":"10.23736\/S0031-0808.25.05339-X","article-title":"Glucagon-like peptide-1 receptor analogues and beyond: Emerging obesity pharmacotherapies","volume":"67","author":"Abburi","year":"2025","journal-title":"Panminerva Medica"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1056\/NEJMoa2032183","article-title":"Once-Weekly Semaglutide in Adults with Overweight or Obesity","volume":"384","author":"Wilding","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1001\/jama.2021.3224","article-title":"Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity","volume":"325","author":"Rubino","year":"2021","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1056\/NEJMoa2206038","article-title":"Tirzepatide Once Weekly for the Treatment of Obesity","volume":"387","author":"Jastreboff","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3400","DOI":"10.1111\/dom.15239","article-title":"A 1-year pilot study of intralymphatic injections of GAD-alum in individuals with latent autoimmune diabetes in adults (LADA) with signs of high immunity: No safety concerns and resemblance to juvenile type 1 diabetes","volume":"25","author":"Hals","year":"2023","journal-title":"Diabetes Obes. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.57237\/j.cmf.2026.01.001","article-title":"Management of Overweight and Obese People with the Dual GIP\/GLP-1 Receptor Agonist Tirzepatide: A Systematic Review","volume":"5","author":"Fu","year":"2026","journal-title":"Clin. Med. Front."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s13679-023-00502-7","article-title":"Beyond Weight Loss: Added Benefits Could Guide the Choice of Anti-Obesity Medications","volume":"12","author":"Guglielmi","year":"2023","journal-title":"Curr. Obes. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/oby.24089","article-title":"Sensory nutrition: Lessons learned and opportunities","volume":"32","author":"Mattes","year":"2024","journal-title":"Obesity"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1002\/oby.24156","article-title":"Combined diet and exercise training decreases serum lipids associated with insulin resistance","volume":"32","author":"Broussard","year":"2024","journal-title":"Obesity"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1111\/dom.70315","article-title":"Association of baseline characteristics with clinical outcomes of tirzepatide treatment in Japanese patients with obesity disease: A subgroup analysis of the SURMOUNT-J trial","volume":"28","author":"Yokote","year":"2025","journal-title":"Diabetes Obes. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1001\/jama.2021.1831","article-title":"Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity","volume":"325","author":"Wadden","year":"2021","journal-title":"JAMA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/dom.16247","article-title":"Novel pharmacotherapies for weight loss: Understanding the role of incretins to enable weight loss and improved health outcomes","volume":"27","author":"Forst","year":"2025","journal-title":"Diabetes Obes. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1080\/14656566.2024.2436595","article-title":"Tirzepatide for overweight and obesity management","volume":"26","author":"Hamza","year":"2024","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yamanouchi, D. (2025). The Roles of Incretin Hormones GIP and GLP-1 in Metabolic and Cardiovascular Health: A Comprehensive Review. Int. J. Mol. Sci., 27.","DOI":"10.20944\/preprints202511.1408.v2"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2710","DOI":"10.1210\/clinem\/dgaa327","article-title":"GIP as a Therapeutic Target in Diabetes and Obesity: Insight From Incretin Co-agonists","volume":"105","author":"Holst","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.molmet.2019.09.010","article-title":"Glucagon-like peptide 1 (GLP-1)","volume":"30","author":"Finan","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1172\/JCI75276","article-title":"The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss","volume":"124","author":"Secher","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/s12933-021-01412-5","article-title":"The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: A novel cardiometabolic therapeutic prospect","volume":"20","author":"Fisman","year":"2021","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/s12933-022-01604-7","article-title":"Tirzepatide, a dual GIP\/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction","volume":"21","author":"Nauck","year":"2022","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1002\/oby.23521","article-title":"Glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, and glucagon receptor poly-agonists: A new era in obesity pharmacotherapy","volume":"30","author":"Malik","year":"2022","journal-title":"Obesity"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3803\/EnM.2023.103","article-title":"Incretin and Pancreatic \u03b2-Cell Function in Patients with Type 2 Diabetes","volume":"38","author":"Ahn","year":"2023","journal-title":"Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3346","DOI":"10.2337\/dc13-0465","article-title":"Secretion of Glucose-Dependent Insulinotropic Polypeptide in Patients with Type 2 Diabetes","volume":"36","author":"Calanna","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"906","DOI":"10.2337\/db18-1123","article-title":"Separate and Combined Glucometabolic Effects of Endogenous Glucose-Dependent Insulinotropic Polypeptide and Glucagon-like Peptide 1 in Healthy Individuals","volume":"68","author":"Gasbjerg","year":"2019","journal-title":"Diabetes"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"678","DOI":"10.2337\/db07-1124","article-title":"Predictors of Incretin Concentrations in Subjects With Normal, Impaired, and Diabetic Glucose Tolerance","volume":"57","author":"Vollmer","year":"2008","journal-title":"Diabetes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1210\/jc.2009-2054","article-title":"Secretion and Dipeptidyl Peptidase-4-Mediated Metabolism of Incretin Hormones after a Mixed Meal or Glucose Ingestion in Obese Compared to Lean, Nondiabetic Men","volume":"95","author":"Carr","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1080\/14656566.2023.2192865","article-title":"GLP-1\/GIP analogs: Potential impact in the landscape of obesity pharmacotherapy","volume":"24","author":"Lafferty","year":"2023","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"126","DOI":"10.37349\/eds.2024.00039","article-title":"Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonists for the treatment of obesity and diabetes mellitus","volume":"2","author":"Martins","year":"2024","journal-title":"Explor. Drug Sci."},{"key":"ref_33","first-page":"e140532","article-title":"Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist","volume":"5","author":"Willard","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zaffina, I., Pelle, M.C., Armentaro, G., Giofr\u00e8, F., Cassano, V., Sciacqua, A., and Arturi, F. (2023). Effect of dual glucose-dependent insulinotropic peptide\/glucagon-like peptide-1 receptor agonist on weight loss in subjects with obesity. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1095753"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/dom.16106","article-title":"Why does GLP -1 agonist combined with GIP and\/or GCG agonist have greater weight loss effect than GLP -1 agonist alone in obese adults without type 2 diabetes?","volume":"27","author":"Jiang","year":"2024","journal-title":"Diabetes Obes. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"57712","DOI":"10.12775\/JEHS.2025.78.57712","article-title":"Glucagon-like peptide 1 receptor agonists in obesity treatment\u2014A literature review","volume":"78","author":"Jentkiewicz","year":"2025","journal-title":"J. Educ. Health Sport"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1007\/s40618-023-02125-0","article-title":"Pharmacological modulation of adaptive thermogenesis: New clues for obesity management?","volume":"46","author":"Genchi","year":"2023","journal-title":"J. Endocrinol. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1042\/CS20160136","article-title":"Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity","volume":"130","author":"Pigeyre","year":"2016","journal-title":"Clin. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1056\/NEJMra1514009","article-title":"Mechanisms, Pathophysiology, and Management of Obesity","volume":"376","author":"Heymsfield","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4158\/EP161365.GL","article-title":"Reviewers of the AACE\/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity","volume":"22","author":"Garvey","year":"2016","journal-title":"Endocr. Pract."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Shin, M.H., Jeong, J.W., Ha, S.E., Singh, R., Lee, M.Y., Ro, S., and Yu, T.Y. (2026). Multidimensional Predictors of Tirzepatide Efficacy: Clinical, Genetic, and Molecular Biomarkers for Glycemic, Weight, and Organ Protection. Pharmaceuticals, 19.","DOI":"10.3390\/ph19050791"},{"key":"ref_42","first-page":"e38379","article-title":"Tirzepatide: A Promising Drug for Type 2 Diabetes and Beyond","volume":"15","author":"Dutta","year":"2023","journal-title":"Cureus"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s13679-017-0262-y","article-title":"Weight Loss and Improvement in Comorbidity: Differences at 5%, 10%, 15%, and Over","volume":"6","author":"Ryan","year":"2017","journal-title":"Curr. Obes. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.tem.2020.02.006","article-title":"How May GIP Enhance the Therapeutic Efficacy of GLP-1?","volume":"31","author":"Samms","year":"2020","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.molmet.2018.12.001","article-title":"Optimized GIP analogs promote body weight lowering in mice through GIPR agonism not antagonism","volume":"20","author":"Mroz","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1007\/s00125-002-0878-6","article-title":"Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients","volume":"45","author":"Krarup","year":"2002","journal-title":"Diabetologia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.2337\/db13-1563","article-title":"Chronic Reduction of GIP Secretion Alleviates Obesity and Insulin Resistance Under High-Fat Diet Conditions","volume":"63","author":"Nasteska","year":"2014","journal-title":"Diabetes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1210\/en.2014-1710","article-title":"An Analysis of Cosecretion and Coexpression of Gut Hormones From Male Rat Proximal and Distal Small Intestine","volume":"156","author":"Svendsen","year":"2015","journal-title":"Endocrinology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.cmet.2018.03.001","article-title":"Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1","volume":"27","author":"Drucker","year":"2018","journal-title":"Cell Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"209ra151","DOI":"10.1126\/scitranslmed.3007218","article-title":"Unimolecular Dual Incretins Maximize Metabolic Benefits in Rodents, Monkeys, and Humans","volume":"5","author":"Finan","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_51","first-page":"199","article-title":"Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes","volume":"52","author":"Knop","year":"2008","journal-title":"Diabetologia"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.2337\/db06-1033","article-title":"Downregulation of GLP-1 and GIP Receptor Expression by Hyperglycemia","volume":"56","author":"Xu","year":"2007","journal-title":"Diabetes"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/nature05482","article-title":"Mechanisms linking obesity to insulin resistance and type 2 diabetes","volume":"444","author":"Kahn","year":"2006","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1007\/s00125-014-3219-7","article-title":"Altered pattern of the incretin effect as assessed by modelling in individuals with glucose tolerance ranging from normal to diabetic","volume":"57","author":"Tura","year":"2014","journal-title":"Diabetologia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1007\/s13300-024-01598-3","article-title":"Addressing the Burden of Multiple Daily Insulin Injections in Type 2 Diabetes with Insulin Pump Technology: A Narrative Review","volume":"15","author":"Brixner","year":"2024","journal-title":"Diabetes Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.molmet.2018.06.003","article-title":"Pancreatic deletion of the interleukin-1 receptor disrupts whole body glucose homeostasis and promotes islet \u03b2-cell de-differentiation","volume":"14","author":"Burke","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/nm727","article-title":"Inhibition of gastric inhibitory polypeptide signaling prevents obesity","volume":"8","author":"Miyawaki","year":"2002","journal-title":"Nat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1016\/S0140-6736(18)32260-8","article-title":"Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: A randomised, placebo-controlled and active comparator-controlled phase 2 trial","volume":"392","author":"Frias","year":"2018","journal-title":"Lancet"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.molmet.2018.09.009","article-title":"LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept","volume":"18","author":"Coskun","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.2337\/db07-1315","article-title":"Separate Impact of Obesity and Glucose Tolerance on the Incretin Effect in Normal Subjects and Type 2 Diabetic Patients","volume":"57","author":"Muscelli","year":"2008","journal-title":"Diabetes"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.2337\/db07-0100","article-title":"Reduced Incretin Effect in Type 2 Diabetes","volume":"56","author":"Knop","year":"2007","journal-title":"Diabetes"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.2337\/diabetes.50.11.2497","article-title":"Reduced Insulinotropic Effect of Gastric Inhibitory Polypeptide in First-Degree Relatives of Patients with Type 2 Diabetes","volume":"50","author":"Meier","year":"2001","journal-title":"Diabetes"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"43062","DOI":"10.1074\/jbc.M111.289009","article-title":"Gastric Inhibitory Peptide Controls Adipose Insulin Sensitivity via Activation of cAMP-response Element-binding Protein and p110\u03b2 Isoform of Phosphatidylinositol 3-Kinase","volume":"286","author":"Mohammad","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.1210\/jcem.86.8.7750","article-title":"Determinants of the Impaired Secretion of Glucagon-Like Peptide-1 in Type 2 Diabetic Patients","volume":"86","author":"Damholt","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.2337\/dc06-1549","article-title":"Incretin Levels and Effect Are Markedly Enhanced 1 Month After Roux-en-Y Gastric Bypass Surgery in Obese Patients With Type 2 Diabetes","volume":"30","author":"Heshka","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1172\/JCI116186","article-title":"Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus","volume":"91","author":"Nauck","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1210\/jcem-24-10-1076","article-title":"Plasma Insulin Response to Oral and Intravenous Glucose Administration1","volume":"24","author":"Elrick","year":"1964","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"E214","DOI":"10.1152\/ajpendo.1979.237.3.E214","article-title":"Glucose clamp technique: A method for quantifying insulin secretion and resistance","volume":"237","author":"DeFronzo","year":"1979","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.beem.2009.03.006","article-title":"Immunoassays for the incretin hormones GIP and GLP-1","volume":"23","author":"Deacon","year":"2009","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1038\/s41591-022-02026-4","article-title":"Two-year effects of semaglutide in adults with overweight or obesity: The STEP 5 trial","volume":"28","author":"Garvey","year":"2022","journal-title":"Nat. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41576-021-00414-z","article-title":"The genetics of obesity: From discovery to biology","volume":"23","author":"Loos","year":"2022","journal-title":"Nat. Rev. Genet."},{"key":"ref_72","first-page":"418","article-title":"Obesity: A multifaceted disease requiring a precision medicine approach","volume":"9","author":"Sorensen","year":"2021","journal-title":"Lancet Diabetes Endocrinol"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/oby.23120","article-title":"Selection of Antiobesity Medications Based on Phenotypes Enhances Weight Loss: A Pragmatic Trial in an Obesity Clinic","volume":"29","author":"Acosta","year":"2021","journal-title":"Obesity"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.cmet.2018.09.022","article-title":"Profound Perturbation of the Metabolome in Obesity Is Associated with Health Risk","volume":"29","author":"Cirulli","year":"2019","journal-title":"Cell Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/4441022a","article-title":"Human Gut Microbes Associated with Obesity","volume":"444","author":"Ley","year":"2006","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.2337\/dc10-0200","article-title":"Common genetic variation in GLP1R and insulin secretion in response to exogenous GLP-1 in nondiabetic subjects: A pilot study","volume":"33","author":"Sathananthan","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.3945\/jn.115.210617","article-title":"Six and 12 Weeks of Caloric Restriction Increases \u03b2 Cell Function and Lowers Fasting and Postprandial Glucose Concentrations in People with Type 2 Diabetes","volume":"145","author":"Sathananthan","year":"2015","journal-title":"J. Nutr."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.cell.2019.03.028","article-title":"Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood","volume":"177","author":"Khera","year":"2019","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1111\/dom.14725","article-title":"Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension","volume":"24","author":"Wilding","year":"2022","journal-title":"Diabetes Obes. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1210\/jc.2011-0266","article-title":"Incretin Hormone and Insulin Responses to Oral Versus Intravenous Lipid Administration in Humans","volume":"96","author":"Lindgren","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1002\/oby.22756","article-title":"Time-Restricted Eating Effects on Body Composition and Metabolic Measures in Humans who are Overweight: A Feasibility Study","volume":"28","author":"Chow","year":"2020","journal-title":"Obesity"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1056\/NEJMoa1607141","article-title":"Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"R823","DOI":"10.1152\/ajpregu.1986.250.5.R823","article-title":"Energy expenditure by doubly labeled water: Validation in humans and proposed calculation","volume":"250","author":"Schoeller","year":"1986","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S2213-8587(18)30051-2","article-title":"Novel subgroups of adult-onset diabetes and their association with outcomes: A data-driven cluster analysis of six variables","volume":"6","author":"Ahlqvist","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/cob.12203","article-title":"A systematic review of reviews: Exploring the relationship between obesity, weight loss and health-related quality of life","volume":"7","author":"Kolotkin","year":"2017","journal-title":"Clin. Obes."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.celrep.2018.10.018","article-title":"Insulin Secretion Depends on Intra-islet Glucagon Signaling","volume":"25","author":"Svendsen","year":"2018","journal-title":"Cell Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"S221","DOI":"10.2337\/diabetes.51.2007.S221","article-title":"Assessing Insulin Secretion by Modeling in Multiple-Meal Tests: Role of potentiation","volume":"51","author":"Mari","year":"2002","journal-title":"Diabetes"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1001\/jama.2016.7602","article-title":"Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis","volume":"315","author":"Khera","year":"2016","journal-title":"JAMA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1056\/NEJMp1405158","article-title":"Updating Cost-Effectiveness\u2014The Curious Resilience of the $50,000-per-QALY Threshold","volume":"371","author":"Neumann","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa1916038","article-title":"A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity","volume":"382","author":"Kelly","year":"2020","journal-title":"N. Engl. J. 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