Scripts for GLP-1, SGLT2 Drugs on the Rise in Type 1 Diabetes Patients

GLP-1 receptor agonist or SGLT2 inhibitor prescribing became more common for people with type 1 diabetes in recent years, a nationwide cross-sectional analysis found.

From 2010 to 2023, the percentage of type 1 diabetes patients prescribed an agent from one of these two classes increased from 0.7% to 8.3%, with the bulk of the increase driven by GLP-1 agonists, reported Hui Shao, MD, PhD, of Emory University Rollins School of Public Health in Atlanta, and colleagues.

The FDA has not approved any SGLT2 inhibitor or GLP-1 receptor agonist for type 1 diabetes, but their use in this patient population “may continue due to the significant weight management and cardiorenal benefits observed in people with and without type 2 diabetes,” they wrote in JAMA.

In their study, the researchers noted that the differences in characteristics for patients prescribed these drug suggest their use “was intended to address additional medical needs.”

For example, GLP-1 agonist users had significantly higher rates of obesity compared with the general type 1 population (69.4% vs 26.8%), while SGLT2 inhibitor users had higher proportions of kidney and cardiovascular disease.

“It is crucial to consider the off-label status of these medications and the associated safety concerns in the type 1 diabetes population before prescribing them,” Shao told MedPage Today, adding that he remains “concerned” since their safety “lacks comprehensive data” in type 1 diabetes.

Indications for SGLT2 inhibitors in type 1 diabetes were withdrawn in Europe due to a risk of euglycemic diabetic ketoacidosis, the researchers noted in their study, while concerns remain about GLP-1 receptor agonists “causing substantial weight loss and increasing the risk of ketoacidosis or hypoglycemia.”

GLP-1 receptor agonists and SGLT2 inhibitors were both initially approved for type 2 diabetes. But over the last several years, GLP-1 agonists have shot to popularity for their weight-loss capabilities, while many SGLT2 inhibitors gained expanded indications for heart and kidney benefits.

The SGLT2 inhibitors empagliflozin (Jardiance) and dapagliflozin (Farxiga) were both rejected by the FDA for type 1 diabetes due to the risks for diabetic ketoacidosis and hypoglycemia.

“My team has received federal funding to examine the safety of using SGLT2 inhibitors and GLP-1 receptor agonists in the type 1 diabetes population,” said Shao. “We will be investigating which subpopulations may safely benefit from these medications. The results are underway.”

For their study, Shao and colleagues identified 943,456 individuals with type 1 diabetes in electronic health records from Epic Cosmos — a database of around 257 million U.S. residents from all 50 states — to evaluate trends in prescribing for GLP-1 agonists and SGLT2 inhibitors from 2010 to 2023.

Prescriptions for GLP-1 agonists increased from 0.3% to 6.6% during the study period. These included prescriptions for dulaglutide (Trulicity), exenatide (Byetta, Bydureon), liraglutide (Victoza, Saxenda), albiglutide and lixisenatide (both now discontinued), semaglutide (Ozempic, Wegovy), and tirzepatide (Mounjaro, Zepbound). Not surprisingly, semaglutide — one of the most popular GLP-1 agents — had the largest growth in off-label prescribing, increasing from 0.2% in 2018 to 4.4% in 2023.

Prescriptions for SGLT2 inhibitors increased from 0.1% to 2.4%. These included canagliflozin (Invokana), dapagliflozin, empagliflozin, and ertugliflozin (Steglatro).

The increasing use of GLP-1 receptor agonists and SGLT2 inhibitors in this population “aligns with what we observe in daily clinical practice and is understandable given the rapidly growing evidence and enthusiasm for these two newer drug classes,” said Shao.

Compared with the general type 1 diabetes population, those newly prescribed a GLP-1 agonist or SGLT2 inhibitor tended to be older (41.5 vs 47.1 vs 56.8 years, respectively).

GLP-1 agonist users had a higher baseline BMI (35 vs 27.5), were more likely to be female (63.2% vs 49.5%), and had higher rates of obesity (69.4% vs 26.8%) than the general type 1 population.

SGLT2 inhibitor users had a higher proportion of chronic kidney disease (26.9% vs 15.9%) and nephropathy (14.9% vs 5.4%) compared with the general type 1 population. They also had higher rates of all heart comorbidities, including myocardial infarction, stroke, heart failure, and ischemic heart disease.

Data on the reason for prescribing these medications was unavailable, the researchers pointed out. Other limitations included the potential for misclassification of some patients with type 1 diabetes and that the dataset only included patients of health systems who used Epic, which may have introduced bias.