Reducing Risk of Diabetic Ketoacidosis in Type 1 Diabetes and Kidney Disease Using Continuous Ketone Monitoring

Summary

The goal of this clinical trial is to develop and evaluate a novel diabetes ketoacidosis risk mitigation strategy to support the safe use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) therapy in participants with type 1 diabetes (T1D) and mild to moderate chronic kidney disease (CKD). The main objectives of this study are to: 1. Evaluate how ketone metrics differ between participants with mild to moderate chronic kidney disease and those with normal renal function in three time periods. 2. Identify potentially modifiable ketosis risk factors. 3. Use continuous glucose monitoring (CGM) and continuous ketone monitoring (CKM) data prior to and following treatment to determine ketosis risk factors and gain knowledge to further refine reporting of risk factors. 4. Gather information on how participants and clinicians like and use the CGM/CKM reports. Participants will be asked to: * Meet with study investigators to determine if they are eligible * Sign written informed consent * Take a pregnancy test, if applicable * Have blood taken to assess kidney function and hemoglobin A1c * Take the study medication, following the study team instructions * Wear the study provided sensor throughout participation. * Complete 5 in person visits, and 11 phone check ins over a nine-month period * Provide feedback on the usefulness of CGM/CKM reports

Timeline

Start

2026-06

Primary completion

2028-05

Completion

2028-08

Publications

• Background Bergenstal RM. Continuous glucose monitoring: transforming diabetes management step by step. Lancet. 2018 Apr 7;391(10128):1334-1336. doi: 10.1016/S0140-6736(18)30290-3. Epub 2018 Feb 16. No abstract available.
• Background Maines E, Pertile R, Cauvin V, Soffiati M, Franceschi R. Glucose metrics improvement in youths with type 1 diabetes using the Ambulatory Glucose Profile report: A real-world study. Diabetes Res Clin Pract. 2024 Jun;212:111720. doi: 10.1016/j.diabres.2024.111720. Epub 2024 May 24.
• Background Huang J, Yeung AM, Bergenstal RM, Castorino K, Cengiz E, Dhatariya K, Niu I, Sherr JL, Umpierrez GE, Klonoff DC. Update on Measuring Ketones. J Diabetes Sci Technol. 2024 May;18(3):714-726. doi: 10.1177/19322968231152236. Epub 2023 Feb 16.
• Background Goldenberg RM, Gilbert JD, Hramiak IM, Woo VC, Zinman B. Sodium-glucose co-transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol. Diabetes Obes Metab. 2019 Oct;21(10):2192-2202. doi: 10.1111/dom.13811. Epub 2019 Jun 30.
• Background Garg SK, Peters AL, Buse JB, Danne T. Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol. Diabetes Technol Ther. 2018 Sep;20(9):571-575. doi: 10.1089/dia.2018.0246. Epub 2018 Aug 21. No abstract available.
• Background Chow E, Clement S, Garg R. Euglycemic diabetic ketoacidosis in the era of SGLT-2 inhibitors. BMJ Open Diabetes Res Care. 2023 Oct;11(5):e003666. doi: 10.1136/bmjdrc-2023-003666.
• Background Wolfsdorf JI, Ratner RE. SGLT Inhibitors for Type 1 Diabetes: Proceed With Extreme Caution. Diabetes Care. 2019 Jun;42(6):991-993. doi: 10.2337/dci19-0008. No abstract available.
• Background Ramphul K, Joynauth J. An Update on the Incidence and Burden of Diabetic Ketoacidosis in the U.S. Diabetes Care. 2020 Dec;43(12):e196-e197. doi: 10.2337/dc20-1258. Epub 2020 Oct 13. No abstract available.
• Background Charleer S, Mathieu C, Nobels F, De Block C, Radermecker RP, Hermans MP, Taes Y, Vercammen C, T'Sjoen G, Crenier L, Fieuws S, Keymeulen B, Gillard P; RESCUE Trial Investigators. Effect of Continuous Glucose Monitoring on Glycemic Control, Acute Admissions, and Quality of Life: A Real-World Study. J Clin Endocrinol Metab. 2018 Mar 1;103(3):1224-1232. doi: 10.1210/jc.2017-02498.
• Background Yau K, Dharia A, Alrowiyti I, Cherney DZI. Prescribing SGLT2 Inhibitors in Patients With CKD: Expanding Indications and Practical Considerations. Kidney Int Rep. 2022 May 5;7(7):1463-1476. doi: 10.1016/j.ekir.2022.04.094. eCollection 2022 Jul.
• Background Simonson GD, Criego AB, Battelino T, Carlson AL, Choudhary P, Franc S, Gershenoff D, Grunberger G, Hirsch IB, Isaacs D, Johnson ML, Kerr D, Kruger DF, Mathieu C, Martens TW, Nimri R, Oser SM, Peters AL, Weinstock RS, Wright EE, Wysham CH, Bergenstal RM. Expert Panel Recommendations for a Standardized Ambulatory Glucose Profile Report for Connected Insulin Pens. Diabetes Technol Ther. 2024 Nov;26(11):814-822. doi: 10.1089/dia.2024.0107. Epub 2024 Jun 10.
• Background Mullen DM, Bergenstal R, Criego A, Arnold KC, Goland R, Richter S. Time Savings Using a Standardized Glucose Reporting System and Ambulatory Glucose Profile. J Diabetes Sci Technol. 2018 May;12(3):614-621. doi: 10.1177/1932296817740592. Epub 2017 Nov 24.
• Background Bergenstal RM, Ahmann AJ, Bailey T, Beck RW, Bissen J, Buckingham B, Deeb L, Dolin RH, Garg SK, Goland R, Hirsch IB, Klonoff DC, Kruger DF, Matfin G, Mazze RS, Olson BA, Parkin C, Peters A, Powers MA, Rodriguez H, Southerland P, Strock ES, Tamborlane W, Wesley DM. Recommendations for standardizing glucose reporting and analysis to optimize clinical decision making in diabetes: the ambulatory glucose profile. J Diabetes Sci Technol. 2013 Mar 1;7(2):562-78. doi: 10.1177/193229681300700234.
• Background Bergenstal RM. Roadmap to the Effective Use of Continuous Glucose Monitoring: Innovation, Investigation, and Implementation. Diabetes Spectr. 2023 Fall;36(4):327-336. doi: 10.2337/dsi23-0005. Epub 2023 Nov 15.
• Background Beck RW, Bergenstal RM, Cheng P, Kollman C, Carlson AL, Johnson ML, Rodbard D. The Relationships Between Time in Range, Hyperglycemia Metrics, and HbA1c. J Diabetes Sci Technol. 2019 Jul;13(4):614-626. doi: 10.1177/1932296818822496. Epub 2019 Jan 13.
• Background Bergenstal RM, Bode BW, Bhargava A, Wang Q, Knights AW, Chang AM. Assessing Time in Range with Postprandial Glucose-Focused Titration of Ultra Rapid Lispro (URLi) in People with Type 1 Diabetes. Diabetes Ther. 2023 Nov;14(11):1933-1945. doi: 10.1007/s13300-023-01476-4. Epub 2023 Sep 23.
• Background Bergenstal RM, Mullen DM, Strock E, Johnson ML, Xi MX. Randomized comparison of self-monitored blood glucose (BGM) versus continuous glucose monitoring (CGM) data to optimize glucose control in type 2 diabetes. J Diabetes Complications. 2022 Mar;36(3):108106. doi: 10.1016/j.jdiacomp.2021.108106. Epub 2021 Dec 31.
• Background Zhang JY, Shang T, Koliwad SK, Klonoff DC. Continuous Ketone Monitoring: A New Paradigm for Physiologic Monitoring. J Diabetes Sci Technol. 2021 Jul;15(4):775-780. doi: 10.1177/19322968211009860. Epub 2021 Apr 9.
• Background Bergenstal RM, Simonson GD, Heinemann L. More Green, Less Red: How Color Standardization May Facilitate Effective Use of CGM Data. J Diabetes Sci Technol. 2022 Jan;16(1):3-6. doi: 10.1177/19322968211053341. Epub 2021 Oct 28. No abstract available.
• Background Tecce N, de Alteriis G, de Alteriis G, Verde L, Tecce MF, Colao A, Muscogiuri G. Harnessing the Synergy of SGLT2 Inhibitors and Continuous Ketone Monitoring (CKM) in Managing Heart Failure among Patients with Type 1 Diabetes. Healthcare (Basel). 2024 Mar 29;12(7):753. doi: 10.3390/healthcare12070753.
• Background Virdi N, Poon Y, Abaniel R, Bergenstal RM. Prevalence, Cost, and Burden of Diabetic Ketoacidosis. Diabetes Technol Ther. 2023 Jun;25(S3):S75-S84. doi: 10.1089/dia.2023.0149.
• Background Danne T, Garg S, Peters AL, Buse JB, Mathieu C, Pettus JH, Alexander CM, Battelino T, Ampudia-Blasco FJ, Bode BW, Cariou B, Close KL, Dandona P, Dutta S, Ferrannini E, Fourlanos S, Grunberger G, Heller SR, Henry RR, Kurian MJ, Kushner JA, Oron T, Parkin CG, Pieber TR, Rodbard HW, Schatz D, Skyler JS, Tamborlane WV, Yokote K, Phillip M. International Consensus on Risk Management of Diabetic Ketoacidosis in Patients With Type 1 Diabetes Treated With Sodium-Glucose Cotransporter (SGLT) Inhibitors. Diabetes Care. 2019 Jun;42(6):1147-1154. doi: 10.2337/dc18-2316. Epub 2019 Feb 6.
• Background Garg SK, Henry RR, Banks P, Buse JB, Davies MJ, Fulcher GR, Pozzilli P, Gesty-Palmer D, Lapuerta P, Simo R, Danne T, McGuire DK, Kushner JA, Peters A, Strumph P. Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes. N Engl J Med. 2017 Dec 14;377(24):2337-2348. doi: 10.1056/NEJMoa1708337. Epub 2017 Sep 13.
• Background Buse JB, Garg SK, Rosenstock J, Bailey TS, Banks P, Bode BW, Danne T, Kushner JA, Lane WS, Lapuerta P, McGuire DK, Peters AL, Reed J, Sawhney S, Strumph P. Sotagliflozin in Combination With Optimized Insulin Therapy in Adults With Type 1 Diabetes: The North American inTandem1 Study. Diabetes Care. 2018 Sep;41(9):1970-1980. doi: 10.2337/dc18-0343. Epub 2018 Jun 24.
• Background Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24.
• Background Bailey CJ, Day C, Bellary S. Renal Protection with SGLT2 Inhibitors: Effects in Acute and Chronic Kidney Disease. Curr Diab Rep. 2022 Jan;22(1):39-52. doi: 10.1007/s11892-021-01442-z. Epub 2022 Feb 3.
• Background Clegg LE, Heerspink HJL, Penland RC, Tang W, Boulton DW, Bachina S, Fox RD, Fenici P, Thuresson M, Mentz RJ, Hernandez AF, Holman RR. Reduction of Cardiovascular Risk and Improved Estimated Glomerular Filtration Rate by SGLT2 Inhibitors, Including Dapagliflozin, Is Consistent Across the Class: An Analysis of the Placebo Arm of EXSCEL. Diabetes Care. 2019 Feb;42(2):318-326. doi: 10.2337/dc18-1871. Epub 2018 Dec 6.
• Background Menne J, Dumann E, Haller H, Schmidt BMW. Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: A systematic review and meta-analysis. PLoS Med. 2019 Dec 9;16(12):e1002983. doi: 10.1371/journal.pmed.1002983. eCollection 2019 Dec.
• Background Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ. Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus: Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications. Circulation. 2016 Sep 6;134(10):752-72. doi: 10.1161/CIRCULATIONAHA.116.021887. Epub 2016 Jul 28.
• Background Neal B, Perkovic V, Matthews DR. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Nov 23;377(21):2099. doi: 10.1056/NEJMc1712572. No abstract available.

Drugs

Indications