Zhiyi Li

Risk factors associated with treatment discontinuation and down-titration in type 2 diabetes patients treated with sulfonylureas

Abstract Objectives: Sulfonylurea therapy among patients with type 2 diabetes mellitus (T2DM) can be disrupted due to adverse events, including hypoglycemia. A retrospective study using the MarketScan claims database quantified the frequency of sulfonylurea discontinuation or down-titration and identified associated risk factors. Research design and methods: Adult patients with an index sulfonylurea prescription between 2008 and 2012 and 1 year continuous enrollment pre- and post-index were included. Therapy changes assessed over 1 year post-index included discontinuation and down-titration. Discontinuation occurred if the date of a fill was >90 days from the end date of the preceding fill. Down-titration occurred when a fill had a lower equivalent dose than the fill on the index date. Kaplan–Meier methods estimated the probability of either discontinuation or down-titration over 12 months, and Cox regression models identified associated risk factors. Results: A total of 104,082 sulfonylurea users were included in the study and the probability of either discontinuation or down-titration at 3, 6 and 12 months was 23.2%, 38.9%, and 52.3%, respectively. Major risk factors associated with therapy changes included post-index hypoglycemia (discontinuation hazard ratio [HR] = 1.78 [1.68, 1.89]; down-titration HR =2.79 [2.40, 3.23]) and concomitant use of insulin (discontinuation HR =1.48 [1.40, 1.57]; down-titration HR =1.82 [1.56, 2.11]). Other risk factors included younger age, female gender, use of second generation sulfonylureas, prior cardiovascular comorbidity and liver disease. Limitations: The study was not able to assess unreported, potentially mild cases of hypoglycemia, nor was it able to evaluate the association between changes in therapy and HbA1c levels or body weight. Conclusions: More than half of T2DM patients who initiated sulfonylurea therapy discontinued or down-titrated within 1 year. Insulin use and hypoglycemia were associated with sulfonylurea therapy change.

Impact of hypoglycemic events and HbA1c level on sulfonylurea discontinuation and down-titration

ABSTRACT Background: A retrospective cohort study using GE Centricity electronic medical records assessed the association between post-index hypoglycemia and HbA1c with discontinuation and down-titration of sulfonylureas among patients with Type 2 diabetes mellitus. Methods: Adult patients with an index prescription for a sulfonylurea and ≥12 months’ continuous records pre- and post-index were eligible. Sulfonylurea discontinuation and down-titration was assessed 1-year post-index. Discontinuation occurred if the date of a prescription was >90 days from the preceding prescription plus days of supply. Down-titration occurred when a subsequent prescription was lower than the index dose. Cox regression assessed the association between post-index hypoglycemia and HbA1c with time to sulfonylurea discontinuation and down-titration, as well as other factors. Results: 28,371 participants were included in the study; 13,459 (47.4%) were discontinuers, 717 (2.5%) were down-titraters, and 14,195 (50.0%) were continuers. 0.6% of continuers experienced hypoglycemia 1-year post-index, compared with 3.1% of down-titraters and 0.8% of discontinuers (p < 0.0001). Patients with post-index hypoglycemia had a significantly higher rate of discontinuation (hazard ratio [HR] = 1.82, 95% CI: 1.47–2.23) and down-titration (HR = 4.25, 95% CI: 1.92–8.03). Patients with higher post-index HbA1c and use of 2nd generation sulfonylureas had an increased rate of discontinuation (HR = 1.05, 95% CI: 1.04–1.06; HR = 1.19, 95% CI: 1.14–1.24, respectively). Conclusion: Approximately half of participants who initiated sulfonylureas discontinued or down-titrated therapy within one year. Both post-index hypoglycemia and higher HbA1c were significant risk factors for sulfonylurea treatment change.