Impact of Hypoglycemia Associated With Antihyperglycemic Medications on Vascular Risks in Veterans With Type 2 Diabetes

OBJECTIVE: Hypoglycemia is associated with failure to show cardiovascular benefit and increased mortality of intensive glycemic control in randomized clinical trials. This retrospective cohort study aimed to examine the impact of hypoglycemia on vascular events in clinical practice. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes were identified by ICD-9-CM codes (250.xx except for 250.x1 and 250.x3) between 1 January 2004 and 1 September 2010 from the Veterans Integrated Service Network 16. Index date was defined as the first date of new antihyperglycemic medications (index treatment). Patients with 1-year preindex records of hypoglycemia, cardiovascular, and microvascular diseases were excluded. The hypoglycemia group was identified by ICD-9-CM codes (250.8, 251.0, 251.1, and 251.2) within the index treatment period. A propensity score–matched group was used as control subjects. Cardiovascular events, microvascular complications, and all-cause death were compared using Kaplan-Meier analysis and Cox proportional hazards regression model. RESULTS: Among the unmatched sample (N = 44,261), the hypoglycemia incidence rate was 3.57/100 patient-years. The matched sample (hypoglycemia group: n = 761; control group: n = 761) had a median follow-up of 3.93 years, mean age of 62.6 ± 11.0 years, and preindex HbA(1c) of 10.69 ± 2.61%. The 1-year change in HbA(1c) was similar (hypoglycemia group −0.51 vs. control group −0.32%, P = 0.7244). The hypoglycemia group had significantly higher risks of cardiovascular events (hazard ratio 2.00 [95% CI 1.63–2.44]) and microvascular complications (1.76 [1.46–2.11]) but no statistical mortality difference. Patients with at least two hypoglycemic episodes were at higher risks of vascular events than those with one episode (1.53 [1.10–1.66]). CONCLUSIONS: Hypoglycemia is associated with higher risks of incident vascular events. Patients with hypoglycemia should be monitored closely for vascular events.