Many with Diabetes Discontinue, Modify Second-Line Therapy within 12 Months of Initiation


New data highlights the need for improved communication and understanding of barriers is evident for the effective management of type 2 diabetes.

David Liss, PhD | Credit: Northwestern Medicine

David Liss, PhD
Credit: Northwestern Medicine

A new study of US adults is shining a spotlight on concerning trends regarding second-line treatments among patients with type 2 diabetes.

Results of the study, which included more than 80,000 patients with type 2 diabetes receiving care between 2014 and 2017, suggest more than 60% of adults experienced treatment modification following initiation of a noninsulin second-line therapy, with 38.6% discontinuing treatment within the first year and nearly 20% requiring treatment intensification.1

“Our results may represent a ‘wake-up call’ for clinicians that many of their patients were not taking the medicines that were prescribed,” said study investigator David Liss, PhD, research associate professor of general internal medicine at Northwestern University Feinberg School of Medicine.2 “While we don't know if providers were aware of the discontinuation events observed in this study, our results highlight the need for ongoing communication between patients and prescribers over time — around medication benefits, side effects and costs — not just at the time of prescribing.”

Since the turn of the century, the diabetes community has experienced an explosion in therapeutic advances, with the approvals for novel classes including, GLP-1 receptor agonists, SGLT2 inhibitors, and DPP-4 inhibitors as adjunct therapies for improving glycemic control. Led by Liss and colleagues from Northwestern University Feinberg School of Medicine designed their research endeavor with the intent of describing changes in antidiabetic medication use and characteristics associated with changes in use following the initiation of noninsulin second-line therapy.1

Sponsored by UnitedHealth Group, the study leveraged nationwide sources of administrative claims data to identify adults with type 2 who were enrolled in a commercial or Medicare Advantage health plan and initiated an index, second-line prescription between January 1, 2014, and June 30, 2017. The specific drug classes of interest for the study were sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, and thiazolidinediones. For the purpose of analysis, investigators assessed discontinuation, switching, and intensification over a 12-month follow-up as their primary outcomes of interest.1

A total of 82,624 patients were identified for inclusion. This cohort was mostly men (54.0%), had a non-Medicare commercial insurance plan (57.0%), and had no diabetes complications (61.5%). The most common second-line medication among the cohort was sulfonylureas (51.0%) followed by DPP-4 inhibitors (24.0%), SGLT2 inhibitors (11.6%), GLP-1 receptor agonists (8.1%), and thiazolidinediones (5.3%).1

Initial analysis revealed 63.6% of the study cohort experienced a treatment modification during the 12-month follow-up. Further analysis indicated 38.6% of patients discounted their second-line therapy, 5.2% switched classes of medication, and 19.8% intensified treatment, with just 36.4% of patients not experiencing any modifications.1

Additional analysis suggested discontinuation was most common among patients initially prescribed GLP-1 receptor agonists, with a discontinuation rate of 50.3%. In contrast, the proportion of patients discontinuing other classes of interest ranged from 34.2% to 39.5%. In adjusted analysis, risk of discontinuation was greater among those prescribed DPP-4 inhibitors (Hazard ratio [HR], 1.09; 95% Confidence interval [CI], 1.04-1.10) and GLP-1 receptor agonists (HR, 1.28; 95% CI, 1.23-1.33) when compared to those prescribed sulfonylureas.1

Investigators highlighted younger patients and female patients had an increased risk of all 3 forms of treatment modifications. Investigators also pointed out index prescription by an endocrinologist was associated with both lower discontinuation risk and higher intensification risk compared to index prescription by a family medicine or internal medicine physician.1

“Our findings highlight the need for new prescribing approaches and to better understand the barriers patients face when taking these medications, to ultimately reduce wasting patients’ time, clinicians’ time and the health system’s money,” Liss added.2


  1. Liss DT, Cherupally M, O’Brien MJ, et al. Treatment Modification After Initiating Second-Line Medication for Type 2 Diabetes. American Journal of Managed Care. 2023;29(12).
  2. Northwestern University. Second-line diabetes meds abandoned by 40% patients. December 12, 2023. Accessed December 19, 2023.
Recent Videos
1 KOL is featured in this Insights series.
Charles C. Wykoff, MD, PhD: Interim Analysis on Ixo-Vec Gene Therapy for nAMD | Image Credit: Retina Consultants of Texas
Sunir J. Garg, MD: Pegcetacoplan Preserves Visual Function on Microperimetry | Image Credit: Wills Eye Hospital
Edward H. Wood, MD: Pharmacodynamics of Subretinal RGX-314 for Wet AMD | Image Credit: Austin Retina Associates
Dilsher Dhoot, MD: OTX-TKI for NPDR in Interim Phase 1 HELIOS Results  | Image Credit: LinkedIn
Katherine Talcott, MD: Baseline EZ Integrity Features Predict GA Progression | Image Credit: LinkedIn
Veeral Sheth, MD: Assessment of EYP-1901 Supplemental Injection Use in Wet AMD | Image Credit: University Retina
Discussing Post-Hoc Data on Ruxolitinib for Nonsegmental Vitiligo, with David Rosmarin, MD
1 KOL is featured in this series.
1 KOL is featured in this series.
© 2024 MJH Life Sciences

All rights reserved.