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.

Keywords:

• Hypoglycemia
• sulfonylureas
• therapy discontinuation
• type 2 diabetes

Transparency

Declaration of funding

This research was funded by Merck & Co. Inc.

Declaration of financial/other relationships

K.I. has disclosed that she is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. P.L. has disclosed that he is an employee of MSD Portugal, Paço de Arcos, Portugal. Y.Q. has disclosed that she was employed by Merck & Co. Inc. at the time of the study, and is now an employee of Novartis Pharmaceutical Company. J.T. and Z.L. have disclosed that they are employees of Asclepius Analytics Ltd., which received fees for consulting from Merck & Co. Inc., Kenilworth, NJ, USA. C.-P.S.F. has disclosed that he 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.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

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

Previous presentations

Iglay K, Qiu Y, Fan C-PS, et al. Risk factors associated with treatment discontinuation and down-titration in type 2 diabetes patients treated with sulfonylureas. 50th EASD Annual Meeting, 15–19 September 2014, Vienna, Austria. Iglay K, Qiu Y, Fan C-PS, et al. Risk factors associated with treatment discontinuation and down-titration in type 2 diabetes patients treated with sulfonylureas. ADA 74th Scientific Sessions, 13–17 June 2014, San Francisco, CA, USA. Laires P, Iglay K, Fan C-PS, et al. Impact of hypoglycemia on discontinuing or down-titrating sulfonylurea among type 2 diabetes patients without insulin use. ISPOR 17th Annual European Congress, 8–12 November 2014, Amsterdam, The Netherlands.