Newswise — People with type 1 diabetes who took GLP-1 receptor agonist (GLP-1-RA) drugs for weight loss or better blood-sugar control had significantly reduced risks of major cardiovascular events and end-stage kidney disease without any increase in safety concerns, according to a study led by researchers at the Johns Hopkins Bloomberg School of Public Health.
The results suggest that the five-year risk of major cardiovascular events such as heart attacks and the risk of end-stage kidney disease were reduced by 15% and 19%, respectively, for the patients taking GLP-1-RA drugs such as semaglutide (Ozempic) and tirzepatide (Mounjaro). For the study, the researchers analyzed electronic health records data on about 175,000 type 1 diabetes patients in the U.S.
About 2 million Americans, including 314,000 children and adolescents, have been diagnosed with type 1 diabetes, according to the Centers for Disease Control and Prevention. The autoimmune disorder destroys the pancreas’s insulin-producing cells and requires lifelong insulin injections to control blood sugar levels.
The risks of side effects of particular concern for type 1 diabetes patients taking GLP-1-RAs—severe hypoglycemia and diabetic ketoacidosis; a severe lack of insulin, causing acid accumulation in the blood—were not increased among the patients taking these drugs.
The findings were published online March 19 in Nature Medicine.
“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,” says study senior author Jung-Im Shin, MD, PhD, an associate professor in the Bloomberg School’s Department of Epidemiology.
Patients with type 1 diabetes face high lifetime risks of cardiovascular and kidney disease. Chronic excess blood sugar promotes atherosclerosis that leads to heart attacks and strokes, and elevated blood-sugar levels can damage the kidney’s urine-filtering structures. There have been few GLP-1-RA clinical trials that measure these outcomes in patients with type 1 diabetes.
Landmark clinical trials have found that GLP-1-RA drugs lower the risks of major cardiovascular events and kidney failure in type 2 diabetes patients by roughly 20%. An estimated 29 million Americans have been diagnosed with type 2 diabetes, according to the CDC.
“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 says.
Two small trials in type 1 diabetes patients a decade ago suggested that the combination of insulin treatment and a GLP-1-RA could cause potentially severe low blood sugar levels (hypoglycemia), and reducing insulin to minimize this risk could cause a different serious complication called diabetic ketoacidosis.
For the new study, the researchers used de-identified electronic health records from a large commercial database covering patients from more than 60 health systems across the U.S. The analysis included 174,678 type 1 diabetes patients and covered January 2013 through March 2024. The team used a “sequential target trial emulation” design—mimicking a clinical trial-type protocol—and accounted for baseline differences between those who began taking GLP-1-RAs and those who didn’t.
The average five-year risk of major cardiovascular events was 4.3% in the GLP-1-RA group vs. 5.0% in the non-GLP-1-RA group, a relative risk reduction of about 15%. The data also suggested a risk reduction of about 21% for heart attacks and 16% for all-cause mortality. The five-year risk of end-stage kidney disease was 1.6% for the GLP-1-RA group vs. 1.9% for the non-GLP-1-RA group, for an estimated relative risk reduction of 19% among those taking GLP-1-RA.
The analysis also found that the GLP-1-RA group had estimated risk reductions of 18% for heart failure, and 28% for major adverse liver events. Patients who initiated GLP-1-RAs also were about 22% more likely to achieve weight loss of at least 10% over five years.
Safety-related outcomes were similarly encouraging. Estimated risks of hospitalization for hypoglycemia and for diabetic ketoacidosis were significantly lower—18% and 17% respectively—in the GLP-1-RA group.
“These findings suggest that physicians are being relatively careful when selecting the type 1 diabetes patients who will receive these drugs, and that the patients are adjusting their insulin doses appropriately,” Shin says. “While our study fills a critical knowledge gap and informs clinical practice for type 1 diabetes patients, ultimately large clinical trials are needed to confirm these findings.”
This study has limitations, including unmeasured confounding due to the nature of observational study design despite the rigorous adjustment methods, and potential misclassification of type 1 diabetes. In addition, only hospitalized cases of hypoglycemia and diabetic ketoacidosis were captured in this study.
“Glucagon-Like Peptide-1 Receptor Agonists for Major Cardiovascular and Kidney Outcomes in Type 1 Diabetes” was co-authored by Yunwen Xu, Natalie Daya Malek, Alexander R. Chang, Justin B. Echouffo-Tcheugui, Elizabeth Selvin, Morgan E. Grams, Michael Fang, and Jung-Im Shin.
Support for the study was provided by the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK139324, R01 DK115534, K01 DK138273).
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