MON-572 Characterization of Individuals With Difficult-to-Control Type 2 Diabetes and Post-Dexamethasone Suppression Test Cortisol Values <1.2, 1.2-1.8, and >1.8 µg/dL: Findings From the CATALYST Part 1 Study

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Abstract Disclosure: R.J. Auchus: Neurocrine Biosciences/Neurocrine UK, LTD, Spruce Biosciences, Corcept Therapeutics, Crinetics Pharmaceuticals, Recordati Rare Diseases, Adrenas Therapeutics, Mineralys Pharmaceuticals, Quest Diagnostics, Xeris Pharmaceuticals, Novo Nordisk, H Lundbeck A/S, Sparrow Pharmaceuticals, Astellas Pharmaceuticals, Acerand Therapeutics. T. Bailey: Abbott Rapid Diagnostics, Biolinq, Corcept Therapeutics, Dexcom, Eli Lilly & Company, Medtronic, Medtrum, Novo Nordisk, Sanofi, Senseonics, VTV Therapeutics, Abbott Diabetes, ACON, CeQur, HAGAR, Intuity Medical, LifeScan, MannKind, Persperion, Sequel Med Tech, Ypsomed. L. Blonde: Bayer, Inc., Corcept Therapeutics, Novo Nordisk. R.S. Busch: Corcept Therapeutics, Eli Lilly & Company, Novo Nordisk, Novartis Pharmaceuticals, Amgen Inc, AstraZeneca, Bayer, Inc. J.B. Buse: Bayer, Inc., Boehringer Ingelheim, Carmot, Eli Lilly & Company, Fractyl, Insulet Corporation, MannKind, Novo Nordisk, VTV Therapeutics, Alkahest, Altimmune, American Diabetes Association, Anji, Aqua Medical Inc, AstraZeneca, CeQur, Dasman Diabetes Center (Kuwait City), embecta, GentiBio, Glyscend, Mediflix, Medscape, Medtronic MiniMed, Mellitus Health, Metsera, Moderna, Pendulum Therapeutics, Praetego, ReachMD, Stability Health, Tandem, Terns Inc., Vertex, Medtronic, Glyscend, PhaseBio, Association for Clinical and Translational Science, Corcept Therapeutics. E.A. Christofides: Chiesi, Eli Lilly & Company, Novo Nordisk, Ascendis, Camurus, Crinetics, Corcept Therapeutics, Recordati, Xeris Pharmaceuticals. R.A. DeFronzo: AstraZeneca, Boehringer Ingelheim, Corcept Therapeutics, Intarcia, Novo Nordisk, Renalytix. B. Eilerman: AbbVie, Corcept Therapeutics, Dexcom, Eli Lilly & Company, Novo Nordisk. V. Fonseca: Corcept Therapeutics, Fractyl, Jaguar Gene Therapy, Abbott, Asahi, Bayer, Inc., Boehringer Ingelheim, BRAVO4Health, Mellitus Health, Amgen Inc. Y. Handelsman: Amgen Inc, Applied Therapeutic, Corcept Therapeutics, Ionis, Lilly USA, LLC, Merck, Regeneron, 89Bio, Arrowhead, AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Esperion, MannKind Pharma, Merck-Pfizer, Novartis Pharmaceuticals, Novo Nordisk, Sanofi. J. Rosenstock: Applied Therapeutics, Boehringer Ingelheim, Eli Lilly & Company, Hanmi, Intarcia, Novo Nordisk, Oramed, Sanofi, Scholar Rock, Structure Therapeutics, Terns Pharma, Zealand, AstraZeneca, Novartis Pharmaceuticals, Merck, Pfizer, Inc. M.H. Shanik: AbbVie, Corcept Therapeutics, Novo Nordisk, Abbott Diabetes, Amgen Inc, Bayer, Inc., Boehringer Ingelheim, Eli Lilly & Company, Xeris Pharmaceuticals. L. Sloan: Amgen Inc, Boehringer Ingelheim, Corcept Therapeutics, Eli Lilly & Company, GlaxoSmithKline, Janssen Research & Development Company, Merck, Novo Nordisk, Sanofi, Abbott, AstraZeneca, Bayer, Inc., Pfizer, Inc. G. Umpierrez: National Institutes of Health (NATS UL 3UL1TR002378-05S2) from the Clinical and Translational Science Award program, National Institutes of Health and National Center for Research Resources (NIH/National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK] 2P30DK111024-06), Abbott, Bayer, Inc., Corcept Therapeutics, Dexcom, Glycare. I.C. Tudor: Corcept Therapeutics. D. Einhorn: Corcept Therapeutics. CATALYST Part 1 (NCT05772169) is the largest, prospective, US-based study to date to evaluate the prevalence of hypercortisolism (HC) in a population with difficult-to-control type 2 diabetes (T2D). HC was defined as 1-mg overnight dexamethasone suppression test (DST) cortisol >1.8 µg/dL in adult participants who had common causes for false-positive DSTs excluded. CATALYST captured data on clinical characteristics associated with a wide range of post-DST cortisol values. This analysis compared the characteristics of CATALYST participants within 3 groups: post-DST cortisol levels <1.2 µg/dL, 1.2-1.8 µg/dL, and >1.8 µg/dL. In CATALYST, difficult-to-control T2D was defined as hemoglobin A1c 7.5-11.5% despite taking ≥3 glucose-lowering medications, taking insulin plus other glucose-lowering medications, or taking ≥2 glucose lowering medications and having micro-/macrovascular complications and/or taking multiple blood pressure-lowering medications. Baseline characteristics were summarized using descriptive statistics. The percentages of post-DST cortisol levels among screened participants (N=1,057) were: <1.2 μg/dL, 51%; 1.2-1.8 μg/dL, 25%; >1.8 μg/dL, 24%. Post-DST cortisol values appeared to follow a normal distribution in both the <1.2 µg/dL and 1.2-1.8 µg/dL groups (within-group mean and median post-DST cortisol values were similar). Across the 3 groups, respectively, higher post-DST cortisol was associated with increased use of sodium-glucose cotransporter 2 (SGLT2) inhibitors (45%, 57%, and 62%) and glucagon-like peptide-1 (GLP-1) analogs (including tirzepatide; 53%, 61%, and 62%). Combination therapy of an SGLT2 inhibitor with insulin (30%, 41%, and 42% in each group, respectively), a GLP-1 analog (22%, 33%, and 35%), or both (14%, 24%, and 23%) was more common in those with higher post-DST cortisol values. Respectively, across the 3 groups, insulin use did not differ (72%, 74%, and 73%), nor did use of metformin (77%, 72%, and 70%), sulfonylureas (31%, 27%, and 26%), or pioglitazone (10%, 13%, and 14%). Higher post-DST cortisol also was associated with progressively higher prevalence of cardiac comorbidities (17%, 29%, and 33% in each group, respectively); renal and urinary disorders, such as chronic kidney disease and nephrolithiasis (20%, 29%, and 33%); and psychiatric disorders (31%, 36%, and 39%). Consistent with previously presented results, the prevalence of obesity was similar across groups. In summary, the post-DST cortisol <1.2 μg/dL group appeared to have fewer comorbidities and used fewer of the newer glucose-lowering medications compared with the other groups. The groups with post-DST cortisol 1.2-1.8 μg/dL and >1.8 μg/dL appeared to have many similarities with regard to medication use and comorbidities. These findings suggest that there is a spectrum of glycemic and cardiovascular risk associated with HC based on post-DST cortisol levels. Presentation: Monday, July 14, 2025

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.