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Beyond Type 2: Emerging CKM Therapies for People with Type 1 Diabetes

  • 1.  Beyond Type 2: Emerging CKM Therapies for People with Type 1 Diabetes

    Posted 2 hours ago

    Beyond Type 2: Emerging CKM Therapies for People with Type 1 Diabetes

    For the past decade, people with type 2 diabetes have benefited from the dramatic increase in treatments approved for reducing cardio-kidney-metabolic risk, including sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) +/- glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists (nsMRAs). These therapies have been shown to reduce heart failure hospitalizations, slow chronic kidney disease (CKD) progression, and lower the risk for cardiovascular events. Unfortunately, people living with type 1 diabetes have not had the same opportunity for benefit and instead continue to rely on the same limited toolkit we’ve had for over three decades: optimizing glycemia, managing blood pressure, renin-angiotensin system (RAS) inhibitors, and statins. People with type 1 diabetes carry 2-4 times the cardiovascular disease risk of the general population, and up to 40% may develop chronic kidney disease despite advances in glucose management.1 The question diabetes care and education specialists (DCES) are increasingly asking: can these same therapies help our patients with type 1 diabetes? The research is evolving, and it's encouraging.

    Finerenone: The FINE-ONE Breakthrough

    The most significant recent development is the FINE-ONE trial, a phase 3 study published in March 2026.2 This trial randomized 242 adults with type 1 diabetes and CKD (eGFR 25-90 mL/min/1.73 m², UACR 200-5000 mg/g) to finerenone (an nsMRA) or placebo, on top of RAS inhibitor therapy. Over six months, finerenone reduced albuminuria by 25% more than placebo (geometric mean ratio 0.75; 95% CI, 0.65–0.87; P0.001). Hyperkalemia occurred in about 10% of finerenone-treated participants, with only 1.7% discontinuing for this reason. Notably, the eGFR dip observed with finerenone (-5.6 mL/min/1.73m2 vs. -2.7 mL/min/1.73m2 [with placebo]) was hemodynamic and reversible during washout, a pattern consistent with findings in type 2 diabetes and to be expected. Finerenone is currently FDA-approved for reducing cardiovascular and kidney risks in adults with CKD associated with type 2 diabetes and for the treatment of heart failure with preserved ejection fraction. It is currently under consideration by the FDA for this expanded indication - adults with type 1 diabetes and CKD.

    GLP-1 and GLP-1/GIP Receptor Agonists: Growing Cardiorenal Evidence

    GLP-1 and GLP-1/GIP receptor agonists are increasingly used off-label in type 1 diabetes, particularly for weight management and insulin dose reduction. A 2026 target trial emulation using national electronic health records from over 174,000 patients with type 1 diabetes found that GLP-1RA initiation was associated with a 15% lower risk of major adverse cardiovascular events (HR 0.85; 95% CI, 0.77-0.95) and a 19% lower risk of end-stage kidney disease (HR 0.81; 95% CI, 0.69-0.95) over five years, without increased risks of DKA or severe hypoglycemia.3

    Phase 3 trials with GLP-1 and GLP-1/GIP receptor agonists are currently underway. For example, the REMODEL T1D trial is investigating semaglutide's effects on kidney disease progression in type 1 diabetes, and the OBES1TY and SURPASS-T1D trials are evaluating semaglutide and tirzepatide respectively in type 1 diabetes with overweight/obesity.

    One helpful resource for DCES that currently exists is the Consensus Report on GLP-1 RAs as Adjunctive Treatment for Individuals With Type 1 Diabetes Using an Automated Insulin Delivery System published in the January 2025 issue of the Journal of Diabetes Science and Technology.4 A follow-on resource “Adjunctive Treatment with GLP/GIPs for Patients with T1D: A Consensus Report and Guidelines for Safe Use” is anticipated soon in the journal Diabetes Technology and Therapeutics.

    None of the GLP-1 +/- GIP RAs are currently FDA-approved for use in people with type 1 diabetes.

    SGLT2 Inhibitors: Promise Tempered by DKA Risk

    SGLT2 inhibitors have shown nephroprotective signals in type 1 diabetes - real-world data demonstrate preserved eGFR and reduced heart failure risk over five years.5 However, the increased risk of DKA remains a significant barrier to regulatory approval.6 Therefore, SGLT2 inhibitors are not currently FDA-approved for type 1 diabetes. That said, the SUGARNSALT trial is investigating sotagliflozin, a dual SGLT1/2 inhibitor, for slowing kidney function decline in type 1 diabetes and concurrent kidney disease, with structured DKA risk mitigation protocols.

    What This Means for Diabetes Care and Education Specialists

    These developments signal a paradigm shift. As educators, staying informed about these therapies is essential - not only to anticipate guideline changes, but to support patients who may already be using GLP-1RAs or SGLT2 inhibitors off-label. Key considerations include educating patients about DKA risk mitigation with SGLT2 inhibitors (e.g. STICH protocol, STOP-DKA protocol), monitoring potassium with finerenone, and recognizing that CKM protection in type 1 diabetes may soon extend well beyond glycemic management.7,8

    The era of CKM-focused care is no longer exclusive to type 2 diabetes. The evidence is building and our patients with type 1 diabetes stand to benefit.

    1. Swamy S, Noor SM, Mathew RO. Cardiovascular Disease in Diabetes and Chronic Kidney Disease. J Clin Med. 2023;12(22):6984.
    2. Heerspink HJL, Birkenfeld AL, Cherney DZI, et al. Finerenone in Type 1 Diabetes and Chronic Kidney Disease. N Engl J Med. 2026;394(10):947-957.
    3. Xu Y, Malek ND, Chang AR, et al. Glucagon-like peptide-1 receptor agonists for major cardiovascular and kidney outcomes in type 1 diabetes. Nat Med. 2026;32(5):1682-1685.
    4. Shah VN, Peters AL, Umpierrez GE, et al. Consensus Report on Glucagon-Like Peptide-1 Receptor Agonists as Adjunctive Treatment for Individuals With Type 1 Diabetes Using an Automated Insulin Delivery System. J Diabetes Sci Technol. 2025;19(1):191-216.
    5. Anson M, Zhao SS, Austin P, Ibarburu GH, Malik RA, Alam U. SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study. Diabetologia. 2023;66(10):1869-1881.
    6. Danne T, Garg S, Peters AL, et al. International Consensus on Risk Management of Diabetic Ketoacidosis in Patients With Type 1 Diabetes Treated With Sodium-Glucose Cotransporter (SGLT) Inhibitors. Diabetes Care. 2019;42(6):1147-1154.
    7. 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;20(9):571-575.
    8. Teng R, Kurian M, Close KL, Buse JB, Peters AL, Alexander CM. Comparison of Protocols to Reduce Diabetic Ketoacidosis in Patients With Type 1 Diabetes Prescribed a Sodium-Glucose Cotransporter 2 Inhibitor. Diabetes Spectr. 2021;34(1):42-51.


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    Andrew Bzowyckyj, PharmD, BCPS, CDCES, FADCES, FAPhA
    Senior Scientific Director, Learning Consultant
    National Kidney Foundation
    Beaverton, OR
    andrew.bzowyckyj@kidney.org
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