(159) Comparing the effects of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on the incidence of neuropathy in patients with type 2 diabetes

Background: : Diabetic neuropathy is a common complication of type 2 diabetes (T2D) affecting up to 50% of these individuals during their lifetime. While the cardiovascular and renal benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been well established, few studies have compared neuropathy-specific outcomes between these drug classes. As a result, their role in preventing diabetic neuropathy remains unclear.

Objective: : To compare the effects of GLP-1RAs and SGLT2is on the onset of neuropathy in patients with T2D.

Methods: : A retrospective cohort study was conducted using de-identified electronic health record (EHR) data from the University of Pittsburgh Medical Center from March 2013 to August 2023. The study included new users of GLP-1RAs or SGLT2i’s with baseline HbA1c ≥6.5% and no prior diagnosis of neuropathy within 1 year before index date (first date of GLP-1RA or SGLT2i ordered on or after March 2014). Patients with < 1 year of pre-index EHR data and those exposed to both drug classes in the follow-up period were excluded. The primary outcome was diagnosis of neuropathy identified by ICD-9 or ICD-10 codes from any visit type. Patients were followed from index until the earliest of neuropathy diagnosis, 2 years post-index, 90 days after the last GLP-1RA or SGLT2i medication order date, or death. GLP-1RA and SGLT2i groups were matched using 1:1 propensity score matching (PSM) on demographics and baseline HbA1c, body mass index, antidiabetic medication use, and clinical conditions. Extended Cox model with time-varying coefficients, restricted mean survival time (RMST), and restricted mean time loss (RMTL) analyses were conducted to compare time to neuropathy incidence between GLP-1RAs and SGLT2is.

Results: : After PSM, 1,790 of the 12,423 eligible patients (1,791 SGLT2i and 10,632 GLP-1RA users) remained in each arm. RMST analysis estimated that over 2 years, GLP-1RA users had an average of 718.8 neuropathy-free days vs 700.8 days in SGLT2i users, with a difference of 18 days favoring GLP-1RA users (95% CI=10.1-26.0 days, P< 0.0001). The Cox model with time interaction resulted in a positive treatment × log(time) interaction coefficient (P < 0.0001), suggesting that the difference in protective effect between GLP-1RAs and SGLT2is narrowed over time.

Conclusions: : Our study suggests that GLP-1RAs may offer modest protective benefits against the development of neuropathy compared to SGLT2i in patients with T2D. Future research should validate these findings with longer follow-up and more refined characterizations of neuropathy.

Sponsorship:: None.