Study Details Effects of Off-Label GLP-1 RA, SGLT2 Inhibitor Use in Type 1 Diabetes

Ildiko Lingvay, MD

A new study is shedding light into the effects of off-label use of GLP-1 receptor agonists and SLGT2 inhibitors for people with type 1 diabetes in real-world settings.

A retrospective chart review of adult patients receiving GLP-1 receptor agonists or SGLT2 inhibitors for more than 90 days, results provide insight into the effects of the agents on body weight, HbA1c, daily insulin usage, and safety outcomes observed with use of either or both of these agents.

“This is the first study comparing outcomes across GLP-1RA and SGLT2i in T1DM and we observed interesting trends both in patient selection, clinical outcomes and safety findings,” wrote investigators.

As the revelations surrounding the cardiovascular and renal protective benefits of GLP-1 receptor agonists and SGLT2 inhibitors in people with type 2 diabetes has become more evident, so has the desire to understand whether the mechanisms of action for both these agents might allow some of this benefit to translate to people with type 1 diabetes. Despite no definitive randomized, placebo-controlled clinical to fully elucidate the effects in people with type 1 diabetes, off-label use of both agents occurs across the US.

In the current study, a trio from University of Texas Southwestern Medical Center led by Ildiko Lingvay, MD, MPH, MSCS, sought to estimate efficacy and safety of this off-label using real-world data obtained from electric health records at their own institution’s medical center in Dallas, TX. Investigators limited their analyses to adult patients with type 1 diabetes who received GLP-1 receptor agonist and/or SGLT2 inhibitor therapy for at least 90 days and with data related to HbA1c, weight, total daily dose of insulin, basal insulin, bolus insulin, total cholesterol, LDL, triglycerides, eGFR, and UACR. The investigators’ analyses included multiple clinical and safety outcomes over the duration of use.

From their search, investigators identified 104 patients who met inclusion criteria. Of these, 65 individuals used GLP-1 receptor agonists exclusively, 28 used SLGT2 inhibitors exclusively, and 11 used both agents either concurrently or sequentially. Investigators pointed out the majority of patients in both groups were non-Hispanic White individuals and women made up the majority of GLP-1 receptor agonist users (72.3%). Investigators also pointed out SGLT2 inhibitors had a greater proportion of users with any albuminuria (31.3% or heart failure (6.3% vs 0%) than GLP-1 receptor agonist users.

Results of the investigators’ analyses indicated GLP-1 receptor agonist use was associated with significant reductions in body weight (90.5kg to 85.4kg, P <.001), HbA1c (7.7% to 7.3%, P=.007), and total daily dose of insulin (61.8 units to 41.9 units, P <.001) at 1 year. Results also indicated SGLT2 inhibitor use was associated with significant reductions in HbA1c (7.9% to 7.3%, P <.001) and basal insulin use (31.3 units to 25.6 units, P=.003) at 1-year among people with type 1 diabetes. When comparing use of the agents against one another, results suggested GLP-1 receptor agonist was associated with greater reductions in body weight than SGLT2 inhibitor use (P=.027), but reductions in HbA1c were similar with use of either agent.

In analyses evaluating safety outcomes, which included a mean total duration of use of 29.5 months per patient for both groups, results indicated users of SGLT2 inhibitors were more likely to experience diabetic ketoacidosis (12.8% vs 3.9%). Additionally, discontinuation due to adverse events was observed among 26.9% of GLP-1 receptor agonist users and 27.7% of SGLT2 inhibitor users.

“GLP-1RA may be a useful addition to insulin as an adjuvant therapy for management of T1DM in clinical practice as it can bring about significant reductions in weight, HbA1c and daily insulin requirements,” wrote investigators. “While SGLT2i demonstrated efficacy in improving HbA1c and reducing basal insulin dose, reductions in weight and TDD insulin demonstrated in clinical trials were not observed in this real-world cohort.”

This study, “Clinical and Safety Outcomes with GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 1 Diabetes: A Real-World Study,” was published in the Journal of Clinical Endocrinology and Metabolism.