New Analysis Examines Long-Term Outcomes of GLP-1 Therapies in Type 1 Diabetes

Use of GLP-1 receptor agonists—with or without glucose-dependent insulinotropic polypeptide (GIP)—may be associated with improved clinical outcomes in patients with Type 1 diabetes, according to a large retrospective analysis published in Diabetes Technology & Therapeutics. Over a two-year period, patients who received these agents had lower all-cause mortality and reduced healthcare utilization compared with matched controls. Rates of diabetic ketoacidosis (DKA) and hypoglycemia were similar between groups.

“We found that using these medications adjunctively to insulin in patients with Type 1 diabetes was associated with very favorable outcomes,” says study author Samita Garg, MD, of Cleveland Clinic. “Specifically, there were lower rates of all-cause mortality and substantially fewer hospitalizations and emergency department visits.”

GLP-1 receptor agonists and dual GLP-1/GIP agonists have rapidly transformed the treatment landscape for Type 2 diabetes and obesity. More recently, clinicians have begun exploring their use in patients with Type 1 diabetes, particularly those with obesity, insulin resistance or features of metabolic syndrome.

“The use of GLP analogs has been growing exponentially for multiple conditions,” Dr. Garg notes. “While they’re currently FDA approved for Type 2 diabetes and weight loss, these medications are increasingly being used off-label in patients with Type 1 diabetes as well as those with both Type 1 and 2 disease or ‘double diabetes.’”

Because existing studies have largely focused on short-term metabolic outcomes, such as glucose control or weight loss, Dr. Garg and colleagues sought to better understand long-term clinical outcomes associated with these therapies among patients with Type 1 diabetes.

A large, real-world cohort

Investigators used the TriNetX multi-institutional database to identify patients based on ICD-10 codes. To better isolate a true Type 1 diabetic population, they excluded individuals with Type 2 diabetes and those taking sodium–glucose cotransporter-2 (SGLT2) inhibitors.

The final analysis included two propensity score–matched cohorts of 4,212 patients each: one receiving a GLP-1 receptor agonist or GLP-1/GIP dual agonist and one not receiving these therapies. Matching accounted for demographics, body mass index (BMI), hemoglobin A1c, and multiple comorbidities. “This was one of the largest studies to date examining long-term outcomes in patients with Type 1 diabetes using these medications,” Dr. Garg says.

Researchers evaluated outcomes over a two-year period, focusing on all-cause mortality and healthcare resource utilization. Secondary outcomes included endoscopy use and prescriptions for gastrointestinal medications such as laxatives and prokinetics.

Over the two-year study period, patients receiving GLP-1–based therapy experienced:

• Significantly lower all-cause mortality
• Fewer hospitalizations
• Fewer emergency department visits
• Reduced endoscopy utilization
• Lower use of gastrointestinal medications, including laxatives and prokinetics

Importantly, the study authors did not observe an increased risk for key diabetes-related complications, including diabetic ketoacidosis and hypoglycemia.

“My initial hypothesis was slightly different,” shares Dr. Garg. “I expected patients using these medications adjunctively with insulin to have potentially more hospitalizations and clinical visits from adverse GI events. Instead, we saw consistent signals of benefit across multiple measures.”

The medications may be particularly beneficial for patients with Type 1 diabetes who also have obesity or metabolic syndrome. “In our propensity-matched cohort, the average BMI in the GLP group was about 34,” according to Dr. Garg. “So, these therapies may be useful for patients who are overweight or obese and have higher insulin requirements.”

Strengths and limitations

A major strength of the analysis is its size and real-world design. By using a large multi-institutional database, the researchers were able to evaluate long-term outcomes in this patient population. Dr. Garg says. “This type of database analysis allows us to get a glimpse at those longer-term outcomes.”

The study also included a range of GLP-1–based medications, from earlier agents such as liraglutide to newer therapies including semaglutide and tirzepatide.

However, the retrospective design carries inherent limitations. Because the data were de-identified, investigators could not confirm medication adherence or review individual charts. Outcomes relied on the accuracy of diagnoses and prescriptions recorded in the database. “We cannot verify with certainty that patients continuously took the medications throughout the study period,” Dr. Garg notes. “That’s one of the limitations of any database study.”

Looking ahead

Overall, the findings add to growing evidence that GLP-1–based therapies could offer benefits beyond glucose control in patients with Type 1 diabetes. “The key takeaway is that using GLP analogs adjunctively with insulin in Type 1 diabetes may be very useful,” Dr. Garg reiterates. “In this study, we saw promising long-term outcomes, including lower mortality and reduced healthcare utilization.”

Further prospective studies will be needed to confirm the findings and clarify which patients are most likely to benefit. Ongoing trials (SURPASS T1D) of newer agents such as tirzepatide may also shed additional light on their role in Type 1 diabetes management.

“These medications may have an important role for some patients with Type 1 diabetes,” concludes Dr. Garg. “As off-label use continues to expand, particularly among patients with obesity or insulin resistance, our findings suggest GLP-1–based therapies may warrant consideration as an adjunct to insulin in carefully selected patients.”