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 2^nd 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.

KEYWORDS:

• Type 2 diabetes
• sulfonylureas
• hypoglycemia
• treatment patterns
• therapy discontinuation
• therapy down-titration
• glycemic control
• persistence study

Acknowledgments

The authors thank Becky Hanna from Asclepius Analytics Ltd. for writing assistance.

Declaration of interest

Funding for this study was provided by Merck & Co., Inc. P Laires is an employee of MSD Portugal, Paço de Arcos, Portugal. K Iglay is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Y Qiu was employed by Merck & Co., Inc. at the time of the study, and is now an employee of Novartis Pharmaceutical Company. J Tang, CPS Fan and Z Li from Asclepius Analytics Ltd. received fees for consulting from Merck & Co., Inc. CPS Fan was employed by Asclepius Analytics Ltd. at the time of the study, and is now an employee of the Hospital for Sick Children, Toronto, ON, Canada. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Supplementary material

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