1896-LB: Clinical Features and C-Peptide Levels Associated with Diabetic Ketoacidosis in Patients with Type 2 Diabetes on Dapagliflozin vs. Placebo—Insights from DECLARE-TIMI 58
Authors: MI KANG YU , MELLONI GIORGIO E.M. , CAHN AVIVIT , RAZ ITAMAR , MOURA FILIPE , BHATT DEEPAK L. , INZUCCHI SILVIO E. , LEITER LAWRENCE A. , MCGUIRE DARREN K. , WILDING JOHN , GAUSE-NILSSON INGRID A. , OSCARSSON JAN , MARSTON NICHOLAS , RUFF CHRISTIAN T. , SABATINE MARC S. , WIVIOTT STEPHEN D. 
Published: June 2024

Introduction: We explored findings associated with the risk of DKA in pts with T2D, with and without dapagliflozin (DAPA).

Methods: DECLARE-TIMI 58 was a CV outcomes trial of 17160 pts with T2D randomized to DAPA vs placebo (PBO) with a median follow-up of 4.2 yrs. Pts with known T1D were excluded. DKA events adjudicated as definite or probable were analyzed.

Results: DKA occurred in 27/8574 pts (0.31%) in DAPA vs 12/8569 (0.14%) in PBO arm (HR 2.18 [1.10-4.30]). Pts who developed DKA were more likely to be insulin users (82.1% vs 40.8%) and had a longer duration of T2D (14 vs 11 yrs), higher HbA1c (9.0% vs 8.0%), lower fasting C-peptide (C-pep; 0.2 vs 1.0 nmol/L) and HOMA2-B (20.7 vs 58.0; P&lt;0.02 for all). 63% of DKA events occurred in pts with fasting C-pep &lt;0.4 nmol/L and no DKA occurred in pts with C-pep &gt;0.97 nmol/L (Fig A). The 4-yr KM rate of DKA in pts with C-pep &lt;0.4 vs ≥0.4 nmol/L was 1.4% vs 0.09% (aHR 15.7 [7.7-32.2]). The absolute risk difference between DAPA and PBO was 1.84% vs 0.07% in pts with C-pep &lt;0.4 vs ≥0.4 nmol/L (Fig B).

Conclusion: In DECLARE-TIMI 58, DKA was rare, and occurred mostly in pts with impaired insulin secretion. In pts with C-pep ≥0.4 nmol/L, the excess in DKA with DAPA was less than 1/1000pts/yr. Further research is needed to determine the utility of prospective C-peptide testing when initiating SGLT2i in pts suspected to have insulin deficiency.

Disclosure

Y. Kang: None. A. Cahn: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk, AstraZeneca, Eli Lilly and Company, Bayer Inc. Advisory Panel; Eli Lilly and Company. I. Raz: Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Johnson & Johnson Medical Devices Companies, Bayer Inc. F. Moura: Consultant; Janssen Pharmaceuticals, Inc. D.L. Bhatt: Advisory Panel; Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed,. Board Member; American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock);. Consultant; Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene. Other Relationship; Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute, Boston Scientific, Cleveland Clinic, Contego Medical, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai, Novartis, Popul, ACC, Arnold and Porter Law Firm, Baim Institute, Belvoir Publications, CSL Behring, Cowen and Company, Duke Clinical Research Institute, HMP Global, Journal of the ACC, K2P, Level Ex, Medtelligence/Re, Population Health Research Institute, Wiley, Clinical Cardiology, Lexicon Pharmaceuticals, Inc. Research Support; Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scienti, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Mode, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio. Other Relationship; Elsevier (Editor, Braunwald’s Heart Disease), Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions, American College of Cardiology, FlowCo. Stock/Shareholder; Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock). S.E. Inzucchi: Consultant; AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc., Pfizer Inc., Novo Nordisk, Bayer Inc. L.A. Leiter: Advisory Panel; Abbott. Other Relationship; Amarin Corporation, Amgen Inc., Applied Therapeutics Inc. Advisory Panel; AstraZeneca. Other Relationship; Bayer Inc. Advisory Panel; Boehringer-Ingelheim. Other Relationship; CRISPR Therapeutics Other, Eli Lilly and Company. Speaker's Bureau; EOCI Pharmacomm. Research Support; ESPERION Therapeutics, Inc. Other Relationship; HLS Therapeutics Inc. Research Support; Kowa Company, Ltd., Lexicon Pharmaceuticals, Inc. Advisory Panel; Merck & Co., Inc. Speaker's Bureau; Novartis AG. Advisory Panel; Novo Nordisk. Other Relationship; Novo Nordisk Canada Inc. Speaker's Bureau; Pfizer Inc. Advisory Panel; Sanofi. Speaker's Bureau; Toronto Knowledge Translation Working Group. Other Relationship; Up-To-Date. D.K. McGuire: Other Relationship; Merck & Co., Inc., Eli Lilly and Company, Boehringer-Ingelheim, Novo Nordisk, Pfizer Inc., AstraZeneca. Consultant; Bayer Inc., Lexicon Pharmaceuticals, Inc., Altimmune Inc., Intercept Pharmaceuticals, Inc., Applied Therapeutics. J. Wilding: Speaker's Bureau; Boehringer-Ingelheim. Consultant; Eli Lilly and Company, Napp Pharmaceuticals Limited, Novo Nordisk. Advisory Panel; AstraZeneca. Consultant; Alnylam Pharmaceuticals, Inc., Rhythm Pharmaceuticals, Inc. Speaker's Bureau; Sanofi. Consultant; A. Menarini Diagnostics. I.A. Gause-Nilsson: Employee; AstraZeneca. J. Oscarsson: Employee; AstraZeneca. Stock/Shareholder; AstraZeneca. N. Marston: Research Support; Ionis Pharmaceuticals, Amgen Inc., Pfizer Inc. C.T. Ruff: Research Support; Anthos, AstraZeneca, Daiichi Sankyo, Janssen Pharmaceuticals, Inc., Novartis AG. Other Relationship; Altimmune Inc. Advisory Panel; Bayer Inc., Merck & Co., Inc., Anthos, Janssen Pharmaceuticals, Inc. M.S. Sabatine: Research Support; Abbott, Amgen Inc. Consultant; Amgen Inc. Research Support; Anthos. Consultant; Anthos. Research Support; AstraZeneca. Consultant; AstraZeneca, Beren Therapeutics. Research Support; Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim. Research Support; Daiichi Sankyo. Consultant; Dr. Reddy's Laboratories. Research Support; Ionis Pharmaceuticals, Merck & Co., Inc. Consultant; Merck & Co., Inc., Moderna, Inc. Research Support; Novartis AG. Consultant; Novo Nordisk. Research Support; Pfizer Inc. Consultant; Precision Biosciences. Research Support; Saghmos Therapeutics. Consultant; Silence Therapeutics. Research Support; Verve Therapeutics. S.D. Wiviott: Consultant; Novo Nordisk, Varian, Icon. Research Support; Amgen Inc., Merck & Co., Inc., AstraZeneca, Pfizer Inc. Other Relationship; Vertex Pharmaceuticals Incorporated, Flagship Pioneering.

Funding

National Institutes of Health (5T32DK007529)