1083 — Sulfonylureas as Second Line Therapy for Type 2 Diabetes among Veterans: Results from a National Longitudinal Cohort Study

Lead/Presenter: Erin Weeda,  COIN - Charleston
All Authors: Weeda E (Health Equity and Rural Outreach Innovation Center, Ralph H Johnson VAMC, Charleston SC), Ward RC (Health Equity and Rural Outreach Innovation Center, Ralph H Johnson VAMC, Charleston SC) Gebregziabher M (Health Equity and Rural Outreach Innovation Center, Ralph H Johnson VAMC, Charleston SC)

Objectives:
Due to conflicting results in previous studies, the association between sulfonylurea medications and safety outcomes among patients with Type 2 diabetes mellitus (T2D) remains unclear. Our objectives were to assess if switching to or adding sulfonylureas increases major adverse cardiovascular events (MACE) or severe hypoglycemia versus remaining on metformin alone. In particular, we assessed whether there were differences in health outcomes by racial and ethnic groups.

Methods:
Retrospective, longitudinal cohort study utilizing Veterans Health Administration (VHA) and Medicare data. Veterans with T2D on metformin monotherapy between 2004-2006 were identified. Follow-up occurred through 2016. Those treated with either metformin plus a second-generation sulfonylurea (N = 45,305) or converted from metformin to a second-generation sulfonylurea (N = 2,813) were compared to those receiving metformin monotherapy (N = 65,550) during follow-up. Hazard ratios (HR) and 95%CI from Cox proportional hazards models were used to measure the association between medication exposure and the outcomes (severe hypoglycemia and MACE), using time-varying exposure measures, where mortality was treated as a competing risk.

Results:
In the full population, switching to or adding a sulfonylurea to metformin was associated with 3 times the risk of severe hypoglycemia versus metformin monotherapy (HR:3.44 ,95%CI: 3.06,3.85 and HR:3.08, 95%CI: 2.77,3.42, respectively). Switching to or adding a sulfonylurea to metformin was associated with a 7-19% higher risk of MACE versus metformin monotherapy (HR:1.07, 95%CI: 1.00,1.14 and HR:1.19, 95%CI; 1.13,1.25, respectively). Stratified analyses by race and ethnicity showed that Hispanic patients were at more than twice the risk of severe hypoglycemia when switching to or adding a sulfonylurea to metformin compared to non-Hispanic White patients (HR: 8.21, 95% CI: 4.48, 15.03) vs. (HR: 3.25, 95% CI: 2.886,3.69) for switching, and (HR: 6.23, 95% CI: 3.52,11.03) vs. (HR: 2.91, 95% CI: 2.59, 3.27) for adding a sulfonylurea.

Implications:
Among all patients, switching to and adding second-generation sulfonylureas was associated with a significant increase in severe hypoglycemia and MACE versus remaining on metformin alone. Of even greater concern, the risk for severe hypoglycemia among Hispanic Veterans was more than twice that of non-Hispanic White Veterans.

Impacts:
In an era where guidelines recommend T2D therapies based on compelling indications, safety outcomes associated with sulfonylurea use should be a key consideration when selecting these therapies. Further, our study suggests that these guidelines may need to take race and ethnicity into account.