GLP-1s Reduce MACE, Kidney Disease for Type 1 Diabetes

Initiating glucagon-like peptide-1 receptor agonists (GLP-1-RAs) in patients with type 1 diabetes (T1D) is associated with significant reductions in major adverse cardiovascular events (MACEs) and end-stage kidney disease (ESKD). Historically, this population was excluded from large-scale clinical trials that established the cardiorenal benefits of GLP-1-RAs in type 2 diabetes, leaving a critical knowledge gap for clinicians and pharmacists managing the approximately 2 million Americans living with the autoimmune disorder.¹

“These risk reductions for heart and kidney disease outcomes are comparable to what we’ve seen for type 2 diabetes patients taking GLP-1 RA drugs, and it’s reassuring that we saw no sign of any new safety issues,” Jung-Im Shin, MD, PhD, an associate professor in the Bloomberg School’s Department of Epidemiology, said in a news release.²

By utilizing a sequential target trial emulation design involving 174,678 patients, researchers found that those taking agents such as semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound) experienced a 15% relative risk reduction in MACEs and a 19% reduction in the risk of developing ESKD over a 5-year period. These findings suggest that the therapeutic advantages of GLP-1-RAs may be effectively extrapolated to T1D, mirroring the roughly 20% risk reductions previously observed in the type 2 population.^1,2

About the Study Results

For pharmacists monitoring therapy, the safety profile of these medications in a T1D context is particularly encouraging, as the study found no increased risk of hospitalization for diabetic ketoacidosis (DKA) or severe hypoglycemia. This addresses a long-standing clinical concern that adjunctive GLP-1 therapy might lead to dangerous insulin-dose imbalances. Instead, the data actually suggested an 18% lower risk of hypoglycemia-related hospitalization and a 17% lower risk for DKA.

Patients in the study who initiated GLP-1-RAs were 22% more likely to achieve a weight loss of at least 10% over 5 years. Clinical reviews suggest that the weight-loss benefits are primarily driven by appetite suppression, which can help break the feedback loop of hyperinsulinemia and insulin resistance.

Experts suggest these outcomes reflect careful patient selection and appropriate insulin dose adjustments by clinicians and patients in real-world settings. Furthermore, the study highlighted broader metabolic benefits, including an 18% lower risk of hospitalization for heart failure and a 28% reduction in major adverse liver events, such as decompensated cirrhosis.

The clinical impetus for these treatments is underscored by the rising prevalence of obesity among patients with T1D, which now mirrors that of the general population and contributes to a state of insulin resistance. Traditional intensive insulin therapy, although necessary for glycemic control, often drives a cycle of weight gain and subsequent increases in total daily insulin requirements.^3,4

The Role of the Pharmacist

Pharmacists play a vital role in the practical implementation of these off-label therapies, particularly regarding insulin titration at the start of treatment. Current clinical recommendations for initiating GLP-1s in T1D suggest an initial 20% reduction in bolus insulin and a 10% reduction in basal insulin to mitigate the immediate risk of hypoglycemia. Although early trials with older agents like liraglutide showed mixed results regarding hemoglobin A_1C reduction, newer weekly agents have demonstrated more robust metabolic impacts.⁴

A separate large-scale retrospective analysis from the Cleveland Clinic corroborated these findings, reporting lower all-cause mortality and significantly reduced healthcare resource utilization, including fewer emergency department visits, among type 1 patients using GLP-1 therapies.³

Despite the promising data, researchers emphasize that these results come from observational electronic health record data and require confirmation through large-scale randomized controlled trials. There are also lingering questions regarding the long-term sustainability of weight loss and the optimal dosing for type 1 patients.^1,2

“The type 1 diabetes population, compared to the type 2 diabetes population, is relatively small and relatively young, so it is inherently difficult to conduct a large-scale clinical trial that can show clear differences in cardiovascular and kidney event rates in this population within a reasonable time,” Shin said in the news release.²

However, the current evidence provides a strong rationale for pharmacists and physicians to consider GLP-1s as a potent strategy for preventing the early-onset cardiovascular and kidney complications that have historically burdened this population. As off-label use continues to grow, particularly for those with features of metabolic syndrome, these medications may represent a significant shift in the standard of care for type 1 diabetes management.^1-4

READ MORE: Diabetes Resource Center

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REFERENCES

1. 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. Published online March 19, 2026. doi:10.1038/s41591-026-04274-0

2. Improved heart and kidney outcomes for type 1 diabetes patients taking GLP-1 weight loss drugs. News release. Johns Hopkins University. March 24, 2026. Accessed May 20, 2026. https://publichealth.jhu.edu/2026/improved-heart-and-kidney-outcomes-for-type-1-diabetes-patients-taking-glp-1-weight-loss-drugs

3. Cleveland Clinic. New analysis examines long-term outcomes of GLP-1 therapies in type 1 diabetes. March 26, 2026. Accessed May 20, 2026. https://consultqd.clevelandclinic.org/new-analysis-examines-long-term-outcomes-of-glp-1-therapies-in-type-1-diabetes

4. Resnick O, Bril F, Beauchamp G. Glucagon-like peptide-1 receptor agonists and type 1 diabetes: a potential game changer?. Front Endocrinol (Lausanne). 2025;15:1520313. Published 2025 Jan 21. doi:10.3389/fendo.2024.1520313