High Out-of-Pocket Costs Linked to Lower Likelihood of SGLT2i, GLP-1 RA Initiation

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Among more than 80,000 older adults with T2D and established CVD, those in the highest quartile of out-of-pocket costs were less likely to initiate a GLP-1 R or SGLT2 inhibitor.

New research suggests patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) in the highest quartile of out-of-pocket costs were less likely to initiate a sodium-glucose cotransporter 2 (SGLT2) inhibitor or glucagon-like peptide-1 receptor agonist (GLP-1 RA).1

Using data from more than 80,000 patients, the results showed those in the highest quartile of out-of-pocket costs were 13% and 20% less likely to initiate a GLP-1 RA or SGLT2 inhibitor, respectively, when compared with those in the lowest quartile of out-of-pocket costs.

“Our findings suggest that high drug costs may independently estimate the likelihood of treatment initiation with an SGLT2 inhibitor or GLP-1 RA, irrespective of a patient’s age, race, degree of glucose control, and the presence of preexisting CVD or other clinical comorbidities,” wrote the investigative team, led by Jing Luo, MD, MPH, from the division of general internal medicine at the University of Pittsburgh School of Medicine.1

Professional guidelines have recommended both treatments for patients with T2D and established CVD based on evidence from large cardiovascular outcomes trials. However, regardless of this, usage of these newer drug classes has been paradoxically suboptimal.2 High out-of-pocket costs can limit the initiation of and adherence to prescribed glucose-lowering therapies, but less is known about the use of these newer therapies.

To better address this gap in evidence, Luo and colleagues analyzed the association between high out-of-pocket costs and the initiation of an SGLT2 inhibitor or GLP-1 RA among adults with T2D and established CVD who are metformin-treated.1 The retrospective cohort study used 2017 - 2021 claims data from the Optum deidentified Clinformatics Data Mart Database. Participants eligible for the study were adults with T2D with ≥1 claim for dispensed metformin between December 2017 - December 2020.

Within the analysis, the primary outcome was treatment intensification, defined as the new dispensing of either an SGLT2 inhibitor or GLP-1 RA among patients treated with metformin monotherapy. The investigative team did not refer to intensification as an increase in the dose of a drug. Moreover, each treatment group was separated into quartiles based on the 30-day mean out-of-pocket cost for SGLT2 inhibitors and GLP-1 RAs.

For each drug class separately, investigators used Cox proportional hazards models adjusting for demographics, clinical comorbidities, insurance type, clinician, and laboratory characteristics to estimate the hazards of treatment intensification, comparing the highest versus the lowest quartile of out-of-pocket costs. Data were analyzed from April 2021 - October 2022.

The cohort included 80,807 adult patients (mean age, 72 years; 45,129 [55.8%] male) with T2D and established CVD on metformin monotherapy. Most patients (n = 71,128 [88%]) were insured with Medicare Advantage. The patient population was followed for a median of 1080 days.

For the overall cohort, data showed the mean estimated out-of-pocket cost for a 30-day supply of a GLP-1 RA and SGLT2 inhibitor was $69.2 and $54.39, respectively. Among those in the GLP-1 RA cohort, patients in the lowest quartile (Q1) saw mean out-of-pocket costs of $25 versus $118 for those in the highest quartile (Q4). Meanwhile, in the SGLT2 inhibitor cohort, patients in Q1 saw out-of-pocket costs of $23 compared with $91 for patients in Q4.

A comparison of patients in Q1 versus Q4 of out-of-pocket costs revealed those with the highest quartile of costs were less likely to initiate both a GLP-1 RA (adjusted hazard ratio [aHR], 0.87; 95% CI, 0.78 - 0.97) or an SGLT2 inhibitor (aHR, 0.80; 95% CI, 0.73 - 0.88). The analysis showed the median number of days to initiate a GLP-1 RA was 481 days in Q1 and 556 days in Q4 of out-of-pocket costs; for SGLT2 inhibitors, the median number of days was 520 in Q1 and 685 in Q4 of out-of-pocket costs.

As a result, patients in the highest out-of-pocket quartile received intensification to guideline-recommended therapies at a median of 3 - 6 months later than those in the lowest out-of-pocket cost quartile. Investigators noted these delays could thus reduce the impact of the therapies on clinical outcomes.

“Such delays may reduce the potential impact of these 2 classes of medications on important clinical outcomes, such as myocardial infarction, stroke, hospitalization for heart failure, and worsening of renal function; thereby resulting in higher downstream costs associated with treating these complications,” investigators wrote.


  1. Luo J, Feldman R, Callaway Kim K, et al. Evaluation of Out-of-Pocket Costs and Treatment Intensification With an SGLT2 Inhibitor or GLP-1 RA in Patients With Type 2 Diabetes and Cardiovascular Disease. JAMA Netw Open. 2023;6(6):e2317886. doi:10.1001/jamanetworkopen.2023.17886
  2. McCoy RG, Lipska KJ, Van Houten HK, Shah ND. Paradox of glycemic management: multimorbidity, glycemic control, and high-risk medication use among adults with diabetes. BMJ Open Diabetes Res Care. 2020;8(1):e001007. doi:10.1136/bmjdrc-2019-001007