Real-World Study Suggests CKM Therapies May Benefit Patients With T1D and CKD

A new real-world analysis suggests that cardio-kidney-metabolic (CKM) therapies, widely used in type 2 diabetes (T2D), may offer meaningful kidney benefits for patients with type 1 diabetes (T1D) and chronic kidney disease (CKD) without increasing key safety risks.¹

The findings, published in Diabetes, Obesity and Metabolism, provide early evidence supporting the potential role of these therapies in a population that has historically lacked targeted treatment options.

“The results of these analyses indicate that CKM therapy is safe and effective in reducing UACR [urine albumin-creatinine ratio] in patients with type 1 diabetes and CKD,” wrote the researchers of their findings.

CKD affects more than 1 in 4 adults with T1D and is a major driver of cardiovascular disease and mortality. Newer therapies such as sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated strong kidney and heart benefits in T2D. The impact of these treatments remains less understood—and unapproved—in T1D, although a proportion of patients receive off-label treatment with these agents, likely reflecting unmet clinical need and growing confidence in their potential benefits.²

To better understand how these therapies perform in real-world settings, researchers analyzed data from Optum’s Market Clarity database, which includes claims and electronic health records for millions of US patients.¹ The study evaluated adults with T1D and CKD between 2016 and 2023, focusing on those who initiated CKM therapies compared with similar patients who did not receive these treatments.

Among more than 337,000 adults with T1D identified in the database, approximately 26% had CKD. Of these, just over 11% were prescribed a CKM therapy during the study period, reflecting growing, though still limited, adoption of these treatments in this population.

The primary measure of effectiveness was change in urinary albumin-to-creatinine ratio (UACR), a key marker of kidney damage and disease progression. Patients receiving CKM therapy achieved meaningful reductions in UACR more quickly than those not receiving these therapies, with an HR of 0.76 (95% CI, 0.61-0.95; P = .0158). These improvements were consistent across different therapy types, including GLP-1 RA and SGLT2 inhibitors used alone.

Further analysis showed that a greater proportion of patients on CKM therapy achieved clinically meaningful reductions in UACR—defined as decreases of 30% (55.3% vs 45.5%; P = .0235), 40% (47% vs 37.8%; P = .0323), or 50% (39.9% vs 31.1%; P = .0513)—compared with the control group.

Safety outcomes were also closely evaluated, particularly given concerns about potential risks such as hypoglycemia and diabetic ketoacidosis (DKA) in patients with T1D. The analysis found no increase in rates of hypoglycemia or DKA among patients receiving CKM therapy compared with those who did not receive the treatments. Notably, there was a trend toward fewer hypoglycemia events among treated patients, although the difference did not reach statistical significance (HR, 0.75; 95% CI, 0.56-1.00).

“We observed a potentially protective effect on hypoglycaemia events among CKM therapy users, which deserves further investigation,” noted the researchers.

Importantly, SGLT2 inhibitors, often associated with increased DKA risk in T1D, did not show a higher incidence of DKA in this real-world cohort. However, researchers cautioned that the relatively small number of events and limited follow-up mean that further study is needed to fully assess long-term safety.

These new findings align with previous clinical trial data in T2D, where CKM therapies have been shown to reduce albuminuria and slow CKD progression. The current study suggests that similar mechanisms, such as reducing intraglomerular pressure and improving metabolic control, may also benefit patients with T1D.

Despite these encouraging results, the authors emphasized that the study’s retrospective design limits its ability to establish causality. Real-world data analyses are subject to potential confounding factors, including differences in patient characteristics and treatment selection.

Looking ahead, several prospective clinical trials are underway to more definitively evaluate the safety and efficacy of CKM therapies in this population, including the REMODEL-T1D and SUGARNSALT studies of GLP-1 RAs and SGLT2 inhibitors, respectively. These include studies examining both kidney and cardiovascular outcomes, which could help inform future treatment guidelines.

References

1. Caramori ML, Repetto E, Perkins C, Pandey A, Rossing P. Cardio-kidney-metabolic therapy use among adults with type 1 diabetes and chronic kidney disease. Diabetes Obes Metab. Published online March 12, 2026. doi:10.1111/dom.70640
2. Li P, Li Z, Staton E, et al. GLP-1 receptor agonist and SGLT2 inhibitor prescribing in people with type 1 diabetes. JAMA. 2024;332(19):1667-1669. doi:10.1001/jama.2024.18581