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Figure 1.  Trends in Use of Medication to Lower Glucose Levels by Health Plan
Trends in Use of Medication to Lower Glucose Levels by Health Plan

Adjusted proportions (ie, predicted probability) of older adults with type 2 diabetes with commercial (solid lines) and Medicare Advantage (dashed lines) health insurance coverage who initiated use of a glucagonlike peptide-1 receptor agonist (GLP-1RA), sodium-glucose cotransporter-2 inhibitor (SGLT2i), or dipeptidyl peptidase-4 inhibitor (DPP-4i) from 2016 to 2019.

Figure 2.  Trends in Use of Medication to Lower Glucose Levels by Older Adults With Comorbidities by Health Plan, 2016 to 2019
Trends in Use of Medication to Lower Glucose Levels by Older Adults With Comorbidities by Health Plan, 2016 to 2019

Solid lines represent commercial insurance coverage; dashed lines, Medicare Advantage coverage. DPP-4i indicates dipeptidyl peptidase-4 inhibitor; GLP-1RA, glucagonlike peptide-1 receptor agonist; HF, heart failure; MI, myocardial infarction; and SGLT2i, sodium-glucose cotransporter-2 inhibitor.

Table 1.  Study Population of Pharmacologically Treated Older Adults With Type 2 Diabetes, 2016 to 2019
Study Population of Pharmacologically Treated Older Adults With Type 2 Diabetes, 2016 to 2019
Table 2.  Factors Associated With Starting New Glucose-Lowering Medications by Older Adults With Type 2 Diabetes, 2016 to 2019a
Factors Associated With Starting New Glucose-Lowering Medications by Older Adults With Type 2 Diabetes, 2016 to 2019a
Table 3.  Adjusted Proportions of Initiation of Medication to Lower Glucose Levels by Insurance Coverage, 2016 to 2019
Adjusted Proportions of Initiation of Medication to Lower Glucose Levels by Insurance Coverage, 2016 to 2019
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Neal  B, Perkovic  V, Mahaffey  KW,  et al; CANVAS Program Collaborative Group.  Canagliflozin and cardiovascular and renal events in type 2 diabetes.   N Engl J Med. 2017;377(7):644-657. doi:10.1056/NEJMoa1611925 PubMedGoogle ScholarCrossref
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Wanner  C, Inzucchi  SE, Lachin  JM,  et al; EMPA-REG OUTCOME Investigators.  Empagliflozin and progression of kidney disease in type 2 diabetes.   N Engl J Med. 2016;375(4):323-334. doi:10.1056/NEJMoa1515920 PubMedGoogle ScholarCrossref
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    Original Investigation
    Diabetes and Endocrinology
    February 1, 2021

    Comparison of Diabetes Medications Used by Adults With Commercial Insurance vs Medicare Advantage, 2016 to 2019

    Author Affiliations
    • 1Division of Community Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota
    • 2Division of Health Care Policy and Research, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
    • 3Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota
    • 4Department of Finance and Medical Industry Leadership Institute, Carlson School of Management, University of Minnesota, Minneapolis
    • 5National Bureau of Economic Research, Cambridge, Massachusetts
    • 6National Clinician Scholars Program, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
    • 7Section of General Internal Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
    • 8Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut
    • 9Center for Outcomes Research and Evaluation, Yale–New Haven Hospital, New Haven, Connecticut
    • 10Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, Mayo Clinic, Rochester, Minnesota
    • 11Knowledge Evaluation Research Unit, Rochester, Minnesota
    • 12OptumLabs, Cambridge, Massachusetts
    JAMA Netw Open. 2021;4(2):e2035792. doi:10.1001/jamanetworkopen.2020.35792
    Key Points

    Question  Were there differences in the initiation of treatment with newer medications to lower glucose levels between patients with type 2 diabetes insured by Medicare Advantage and those insured by commercial health plans from 2016 to 2019?

    Findings  In this cohort study of 382 574 adults with type 2 diabetes aged 58 to 66 years, rates of initiation of glucagonlike peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and dipeptidyl peptidase-4 inhibitors were lower among Medicare Advantage enrollees than among commercial health insurance plan enrollees.

    Meaning  These findings suggest that a better understanding of nonclinical factors contributing to treatment selection and efforts to promote equity in diabetes management are needed.

    Abstract

    Importance  Glucagonlike peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i) are associated with low rates of hypoglycemia, and postmarketing trials of GLP-1RA and SGLT2i demonstrated that these medications improved cardiovascular and kidney outcomes.

    Objective  To compare trends in initiation of treatment with GLP-1RA, SGLT2i, and DPP-4i by older adults with type 2 diabetes insured by Medicare Advantage vs commercial health plans.

    Design, Setting, and Participants  This retrospective cohort study used administrative claims data from a deidentified database of commercially insured and Medicare Advantage beneficiaries. Adults aged 58 to 66 years with type 2 diabetes who filled any medication prescription to lower glucose levels from January 1, 2016, to December 31, 2019, were compared between groups.

    Exposure  Enrollment in a Medicare Advantage or commercial health insurance plan.

    Main Outcomes and Measures  The odds of initiating GLP-1RA, SGLT2i, and DPP-4i treatment were examined for Medicare Advantage vs commercial insurance beneficiaries using 3 separate logistic regression models adjusted for year and demographic and clinical factors. These models were used to calculate adjusted annual rates of medication initiation by health plan.

    Results  A total of 382 574 adults with pharmacologically treated type 2 diabetes (52.9% men; mean [SD] age, 62.4 [2.7] years) were identified, including 172 180 Medicare Advantage and 210 394 commercial beneficiaries. From 2016 to 2019, adjusted rates of initiation of GLP-1RA, SGLT2i, and DPP-4i treatment increased among all beneficiaries, from 2.14% to 20.02% for GLP-1RA among commercial insurance beneficiaries and from 1.50% to 11.44% among Medicare Advantage beneficiaries; from 2.74% to 18.15% for SGLT2i among commercial insurance beneficiaries and from 1.57% to 8.51% among Medicare Advantage beneficiaries; and from 3.30% to 11.71% for DPP-4i among commercial insurance beneficiaries and from 2.44% to 7.68% among Medicare Advantage beneficiaries. Initiation rates for all 3 drug classes were consistently lower among Medicare Advantage than among commercial insurance beneficiaries. Within each calendar year, the odds of initiating GLP-1RA treatment ranged from 0.28 (95% CI, 0.26-0.29) to 0.70 (95% CI, 0.65-0.75) for Medicare Advantage and commercial insurance beneficiaries, respectively; SGLT2i, from 0.21 (95% CI, 0.20-0.22) to 0.57 (95% CI, 0.53-0.61), respectively; and DPP-4i, from 0.37 (95% CI, 0.34-0.39) to 0.73 (95% CI, 0.69-0.78), respectively (P < .001 for all). The odds of starting GLP-1RA and SGLT2i increased with income; for an income of $200 000 and higher vs less than $40 000, the odds ratio for GLP-1RA was 1.23 (95% CI, 1.15-1.32) and for SGLT2i was 1.16 (95% CI, 1.09-1.24).

    Conclusions and Relevance  These findings suggest that Medicare Advantage beneficiaries may be less likely than commercially insured beneficiaries to be treated with newer medications to lower glucose levels, with greater disparities among lower-income patients. Better understanding of nonclinical factors contributing to treatment decisions and efforts to promote greater equity in diabetes management appear to be needed.

    Introduction

    Type 2 diabetes is one of the most common and serious chronic health conditions in the US,1 with a disproportionately high burden of disease among older adults. More than 1 in 4 older adults have diabetes (26.8% of US residents 65 years or older),1 and nearly 90% of older adults with a diagnosis of diabetes are taking medications to lower glucose levels.2 Optimal diabetes management is predicated on controlling hyperglycemia, avoiding hypoglycemia, and using medications associated with the greatest benefit and the least risk of harm when contextualized against each patient’s preferences and situation. Although metformin is consistently recommended as the first-line drug in the management of type 2 diabetes, clinical guidelines advise that the choice of second-line therapy to be used when metformin is either no longer sufficient or is not tolerated is informed by the presence of key comorbidities (ie, cardiovascular disease, heart failure, and nephropathy or chronic kidney disease), risk for hypoglycemia, and considerations of affordability.3-7 Three classes of medications to lower glucose levels were introduced into practice during the past 2 decades. Glucagonlike peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i) are associated with low rates of hypoglycemia, and postmarketing trials of GLP-1RA and SGLT2i also demonstrated that these drugs improved cardiovascular, kidney, and mortality outcomes.8-21

    Medicare Advantage, also called Medicare Part C, is an all-in-one private alternative to traditional (fee-for-service) Medicare, a national health insurance program for retirees, people with disabilities, and patients with end-stage kidney disease requiring dialysis. Medicare Advantage plans are funded by capitated payments from the federal government to private insurance companies to provide Medicare beneficiaries with health insurance that approximates commercial insurance plans for the population younger than 65 years. In addition to covering all services reimbursed by traditional Medicare, 90% of Medicare Advantage plans include an integrated prescription drug benefit, and many plans offer coverage for vision, hearing, dental, and wellness programs.22 In recent years, enrollment in Medicare Advantage plans has been steadily increasing by nearly 9% annually.22 Currently, 36% of all Medicare beneficiaries (24.1 million of 67.7 million people) are enrolled in Medicare Advantage plans, with as many as 51% expected to be enrolled by 2030.22 The increasing popularity of Medicare Advantage plans calls for better understanding of the use of prescription drugs, particularly by patients with common chronic health conditions such as diabetes.

    Data regarding diabetes management for people with Medicare Advantage vs commercial health insurance coverage are scarce. McCoy et al23 previously found low rates of early adoption of SGLT2i among enrollees in Medicare Advantage plans compared with commercial plans. With greater experience using SGLT2i medications and emerging evidence supporting their preferred use in the context of heart failure and nephropathy, prescribing practices may have changed. Moreover, whether use patterns of other potentially preferred medications to lower glucose levels, specifically GLP-1RA, which would be favored in the presence of cardiovascular and kidney disease, differ between Medicare Advantage and commercial enrollees is unknown. To address this knowledge gap with important implications for health policy and health benefit design, we examined the trends in initiation of GLP-1RA, SGLT2i, and DPP-4i treatment among Medicare Advantage and commercial health plan beneficiaries with type 2 diabetes aged 58 to 66 years from 2016 to 2019, hypothesizing that despite the emerging data, these medications will continue to be used less frequently by Medicare Advantage enrollees.

    Methods
    Study Design

    This retrospective cohort study assessed deidentified administrative claims data from OptumLabs Data Warehouse, which includes medical and pharmacy claims and enrollment records for commercial insurance plan and Medicare Advantage enrollees.24-26 The OptumLabs Data Warehouse contains longitudinal health information on enrollees, representing a diverse mixture of ages, races/ethnicities, and geographic regions across the US. This study was exempt from review by the Mayo Clinic institutional review board because it involved research on preexisting and deidentified data. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline.27

    Study Population

    We included all enrollees with type 2 diabetes aged 58 to 66 years who filled any medication prescription to lower glucose levels (eTable 1 in the Supplement) from January 1, 2016, to December 31, 2019. This age range was selected empirically by requiring that at least 1% of beneficiaries in each 1-year age subset have both Medicare Advantage and commercial insurance coverage to minimize bias when comparing between health plans (eFigure in the Supplement). For patients in the GLP-1RA, SGLT2i, and DPP-4i cohorts, the index date was set at the first prescription fill for a drug in each class that was preceded by a 12-month period of uninterrupted health insurance coverage without a prescription fill for any drug in the same therapeutic class. For all other patients, the index date was set at the first prescription fill of any drug that was preceded by 12 months of uninterrupted health insurance coverage. Diabetes was ascertained using Healthcare Effectiveness Data and Information Set claims–computable criteria28 applied to the 12-month period preceding the index date.

    Diabetes type was ascertained based on codes from the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), and the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), and prescriptions for medications filled during the 12 months preceding the index date, consistent with previously described methods.23,29,30 Patients with type 1 diabetes were excluded. In brief, type 1 diabetes was assumed for patients who had (1) more type 1 than type 2 diabetes diagnosis codes on evaluation and management visit claims and insulin claims or (2) an equal number of type 1 and type 2 diabetes diagnosis codes, bolus insulin claims, and no sulfonylurea claims. Codes indicative of type 1 diabetes included ICD-9-CM 250.x1 and 250.x3 and ICD-10-CM codes E10.xxx and O24.0xx. Codes indicative of type 2 diabetes included ICD-9-CM 250.x0 and 250.x2 and ICD-10-CM E11.xxx and O24.1xx. Evaluation and management visits were identified by Current Procedural Terminology codes 99201 to 99499.

    Outcomes

    First starts (initiation) of GLP-1RA, SGLT2i, and DPP-4i treatment were independently ascertained from pharmacy prescription fills, requiring no fills for the same drug class during the preceding 12-month period (but allowing fills for any other drug class, including the other classes of interest). Medication use was classified as first line if there were no prescription fills for any classes of glucose-lowering medications in the preceding 12 months. The 3 outcomes were examined separately and were not mutually exclusive. These medication classes have the same formulary designations in Medicare Advantage and commercial insurance plans.31

    Other Covariates

    Explanatory variables included enrollment in a Medicare Advantage vs commercial health plan. Patient characteristics ascertained at the time of the index date included age, sex, race/ethnicity, US region of residency, and annual household income. Clinical variables included specialty of the physician prescribing the index medication (ascertained based on the National Provider Identifier or the Drug Enforcement Administration number on the pharmacy claim); therapeutic classes of medications with prescriptions filled within 120 days before the index date categorized according to eTable 1 in the Supplement, with combination medications counted toward each component therapeutic class and patients without any baseline medications categorized as having none; whether the index medication was used as first- or second-line treatment; the calendar year of initiation of the index drug; and comorbidities ascertained from all claims during the 12 months preceding the index date. For comorbidities, we considered the total count of diabetes-related complications ascertained using the Diabetes Complications Severity Index (retinopathy, nephropathy, neuropathy, cerebrovascular disease, cardiovascular disease, and peripheral vascular disease)32 and the individual presence of myocardial infarction, cerebrovascular disease, heart failure, nephropathy, retinopathy, neuropathy, peripheral vascular disease, dementia, chronic obstructive pulmonary disease, cirrhosis, cancer (except for skin cancer), and severe hypoglycemia and hyperglycemia, both of which were ascertained from primary diagnoses on emergency department or hospital claims only. Diagnosis codes used to define these comorbidities are detailed in eTable 2 in the Supplement. These covariates were selected based on their clinical relevance and prior literature demonstrating their potential association with choice of therapy to lower glucose levels.

    Statistical Analysis

    Characteristics of patients treated with GLP-1RA, SGLT2i, DPP-4i, and all pharmacological therapies are reported as frequencies with percentages for categorical data and means with SDs or medians with interquartile ranges (IQRs) for continuous variables. Data were compared using unpaired t tests for continuous variables and χ2 tests for categorical variables. Univariate logistic regression models compared those who initiated GLP-1RA, SGLT2i, and DPP-4i treatment with those who did not initiate these treatments.

    Three separate multivariate logistic regression models were used to assess factors associated with GLP-1RA, SGLT2i, and DPP-4i initiation compared with no initiation, with results presented as odds ratios (ORs) and 95% CIs. Model covariates included the covariates detailed above, with missing data included as a separate category (unknown), and interaction terms between year and health plan. These models were then used to calculate predicted probabilities of initiation of GLP-1RA, SGLT2i, and DPP-4i treatment in each calendar year by health plan among all patients and in subgroups of patients with myocardial infarction, cerebrovascular disease, stroke, and nephropathy. Two-sided P < .05 indicated statistical significance. All analyses were conducted using SAS Enterprise Guide, version 9.4 (SAS Institute).

    Results

    We identified 382 574 adults aged 58 to 66 years with prescriptions for pharmacological treatment for type 2 diabetes (52.9% men and 47.1% women; mean [SD] age, 62.4 [2.7] years), including 172 180 (45.0%) with Medicare Advantage and 210 394 (55.0%) with commercial insurance. The mean (SD) age of Medicare Advantage beneficiaries was 63.4 (2.7) years; 53.7% were women, 49.8% were White, and 40.2% had an annual household income of less than $40 000 (Table 1). In contrast, patients with commercial insurance were younger, with a mean (SD) age of 61.5 (2.4) years; 41.7% were women, 66.0% were White, and 18.6% had an annual household income of less than $40 000. Medicare Advantage beneficiaries had a greater burden of diabetes-related complications, with 39.6% of Medicare Advantage and 16.4% of commercial beneficiaries having 2 or more complications.

    Overall, 6.6% of Medicare Advantage beneficiaries and 9.7% of commercial beneficiaries started GLP-1RA treatment during the study period; 4.7% of Medicare Advantage beneficiaries and 9.8% of commercial beneficiaries started SGLT2i treatment; and 5.7% of Medicare Advantage beneficiaries and 7.2% of commercial beneficiaries started DPP-4i treatment. Characteristics of patients starting treatment with these 3 drug classes are detailed in eTables 3 to 5 in the Supplement.

    As shown in Table 2, Table 3, and Figure 1, adjusted rates of GLP-1RA initiation increased steadily from 2016 to 2019, from 2.14% to 20.02% among commercial beneficiaries (OR, 11.44; 95% CI, 10.92-11.98) and from 1.50% to 11.44% among Medicare Advantage beneficiaries (OR, 8.46; 95% CI, 7.87-9.11). Similarly, adjusted rates of SGLT2i initiation increased from 2.74% to 18.15% among commercial beneficiaries (OR, 7.87; 95% CI, 7.53-8.23) and from 1.57% to 8.51% among Medicare Advantage beneficiaries (OR, 5.83; 95% CI, 5.39-6.30). Initiation rates for DPP-4i increased less steeply, from 3.30% to 11.71% among commercial beneficiaries (OR, 3.89; 95% CI, 3.70-4.09) and from 2.44% to 7.68% among Medicare Advantage beneficiaries (OR, 3.33; 95% CI, 3.10-3.57). Within each calendar year, the odds of medication initiation were significantly lower for Medicare Advantage beneficiaries than for commercial beneficiaries, ranging from ORs of 0.28 (95% CI, 0.26-0.29) to 0.70 (95% CI, 0.65-0.75) for GLP-1RA, 0.21 (95% CI, 0.20-0.22) to 0.57 (95% CI, 0.53-0.61) for SGLT2i, and 0.37 (95% CI, 0.34-0.39) to 0.73 (95% CI, 0.69-0.78) for DPP-4i.

    In addition to differences in initiation of medication by health plan, we found that older patients were less likely to start treatment with each of the examined medications than were younger patients, with ORs ranging from 0.92 (95% CI, 0.92-0.93) for GLP-1RA to 0.95 (95% CI, 0.95-0.96) for DPP-4i for each additional year of age. Women were more likely than men to start GLP-1RA (OR, 1.44; 95% CI, 1.40-1.48) and DPP-4i (OR, 1.08; 95% CI, 1.05-1.11) treatment but less likely to start SGLT2i treatment (OR, 0.91; 95% CI, 0.89-0.94). Compared with White patients, all non-White patients were less likely to start GLP-1RA treatment (OR for Black patients, 0.96 [95% CI, 0.92-0.99]; OR for Hispanic patients, 0.86 [95% CI, 0.83-0.90]; OR for Asian patients, 0.49 [95% CI, 0.45-0.54]), and Asian patients were also less likely to start SGLT2i treatment (OR, 0.91; 95% CI, 0.84-0.99). In contrast, Black (OR, 1.16; 95% CI, 1.12-1.21), Hispanic (OR, 1.18; 95% CI, 1.13-1.23), and Asian (OR, 1.17; 95% CI, 1.08-1.27) patients were all more likely than White patients to start DPP-4i. Patients with annual household incomes of $200 000 or higher were more likely to start GLP-1RA (OR, 1.23; 95% CI, 1.15-1.32) and SGLT2i (OR, 1.16; 95% CI, 1.09-1.24) treatment than were patients with lower household incomes lower than $40 000 (Table 2).

    We also examined rates of initiation of GLP-1RA, SGLT2i, and DPP-4i treatment in subgroups of patients with comorbid health conditions that may call for preferential use of these medication classes. Patients with nephropathy, who would benefit from GLP-1RA and SGLT2i therapy, were more likely to start GLP-1RA treatment than were patients without nephropathy (OR, 1.17; 95% CI, 1.11-1.22) but were less likely to start a SGLT2i treatment (OR, 0.76; 95% CI, 0.73-0.80) (Table 2). Patients with a history of myocardial infarction, who would benefit from GLP-1RA therapy, were equally likely to start GLP-1RA treatment as were those without such history (OR, 0.96; 95% CI, 0.90-1.03). Patients with cerebrovascular disease, who would also benefit from GLP-1RA therapy, were less likely to start it (OR, 0.92; 95% CI, 0.87-0.98). Patients with heart failure, who would benefit from SGLT2i therapy and may be harmed by DPP-4i therapy, were equally likely to start a SGLT2i (OR, 0.95; 95% CI, 0.90-1.10) but were more likely to start a DPP-4i (OR, 1.11; 95% CI, 1.05-1.17) than patients without heart failure. Temporal trends in the adjusted initiation rates of medication use by patients with these 4 comorbidities paralleled that of the overall population (Figure 2), with persistent differences in initiation between Medicare Advantage and commercial insurance enrollees.

    Discussion

    Contemporary approaches to managing type 2 diabetes take into consideration not only the need to control hyperglycemia but also the effects that chosen therapies may have on outcomes that matter to people with diabetes, such as cardiovascular events, kidney disease progression, and death.3-6 With 2 classes of medications—GLP-1RA and SGLT2i—shown to improve cardiovascular, kidney, and mortality outcomes among patients with type 2 diabetes, it was imperative to understand whether nonclinical factors, such as health insurance type, are associated with differences in medication use patterns. In this analysis of claims data for 382 574 older adults, we found that Medicare Advantage beneficiaries were significantly less likely to start GLP1-RA, SGLT2i, and DPP-4i treatment than were patients with commercial health insurance plans despite similar formulary designs.31

    This is the first study, to our knowledge, to demonstrate the magnitudes of difference in the use GLP-1RA, SGLT2i, and DPP-4i between similarly aged enrollees in Medicare Advantage and commercial health insurance plans. These medications are not new and have a robust evidence base for their efficacy and safety, yet their use continues to lag among Medicare Advantage beneficiaries, including those who are most likely to benefit from them. Although we do not suggest an optimal rate of GLP-1RA, SGLT2i, or DPP-4i use, the gaps in their initiation among patients with preexisting high-risk conditions, such as myocardial infarction, cerebrovascular disease, heart failure, and nephropathy, suggest that an opportunity exists to improve diabetes management and health outcomes among Medicare Advantage beneficiaries.

    Our findings also revealed racial/ethnic disparities in GLP-1RA use. Compared with White patients, Black, Hispanic, and Asian patients were less likely to start GLP-1RA treatment. Although there was no association between Black or Hispanic race/ethnicity and initiation of SGLT2i treatment after all other demographic and clinical factors were accounted for, Asian patients remained less likely to start SGLT2i treatment as well. Low adoption rates of new medications by Black patients have been documented previously,23,33,34 and these low rates may be associated with increased disparities in diabetes health outcomes.35 However, rates of initiation of DPP-4i treatment were higher among racial/ethnic minority groups than among White patients. Dipeptidyl peptidase-4 inhibitors are not as effective at lowering hemoglobin A1c levels as either GLP-1RA or SGLT2i, nor do they have the same beneficial cardiovascular or kidney effects.3 Why DPP-4i treatment is started more frequently by patients who are more likely to benefit from alternative medication classes and why initiation rates are higher among racial/ethnic minorities is unknown. Until recently, some guidelines4 recommended DPP-4i as second-line therapy preferred to GLP-1RA or SGLT2i owing to the benign adverse effect profile and ease of administration of the drug class (ie, oral formulation), but with emergence of robust efficacy data for GLP-1RA and SGLT2i, these 2 classes are now increasingly preferred to DPP-4i medications.3,7 A more nuanced understanding of factors associated with medication preferences, including qualitative exploration of clinicians’ and patients’ attitudes and beliefs about the selection of medication to lower glucose levels, therefore appears to be needed.

    We hypothesize that some of the differences in the use of GLP-1RA, SGLT2i, and DPP-4i medications may be associated with affordability because all are costly brand-name medications. Patients with Medicare Advantage plans are ineligible for manufacturer savings cards and, at some point during the year, may face a “donut hole” with limited or no prescription drug coverage, both of which may make out-of-pocket cost-sharing expenses more unaffordable for them than for commercial insurance enrollees. A total of 40.2% of Medicare Advantage beneficiaries in the present cohort had an annual household income below $40 000 compared with 18.6% of commercial beneficiaries, and lower incomes were significantly associated with decreased the odds of initiating GLP-1RA and SGLT2i treatment. We did not observe a consistent association between income and initiation of DPP-4i treatment, however, potentially because DPP-4i medications are less costly than GLP-1RA and SGLT2i medications even if they are more expensive than generic alternatives.3 Lower income is associated with worse glycemic control and diabetes-related health outcomes compared with higher incomes,36-42 and financial barriers to optimal pharmacotherapy may contribute to these differences.

    Limitations

    This study has limitations. It relied on data from commercial insurance and Medicare Advantage plans offered by a single, large, national health insurance company, which allowed for direct comparisons between commercial insurance and Medicare Advantage plans, but results may not generalize to other private and public health plans. Our analyses focused on initiation of medication rather than adherence and persistence, and as such, our findings likely underestimate the association of cost-related barriers with evidence-based medication use. We were unable to capture medications obtained as samples or through manufacturer financial assistance programs, which may underestimate the use of costly medications, particularly among individuals in lower-income households. We were also unable to identify the clinical contexts (including hemoglobin A1c level) and shared decision-making conversations between patients and their clinicians that may have affected medication choice and differed between commercial insurance plan and Medicare Advantage enrollees. Thus, these findings suggest the need for better understanding of factors contributing to treatment decisions and efforts to improve affordability and equity in the use of glucose-lowering therapies by all patients with diabetes.

    Conclusions

    Our study identified gaps in the use of effective, safe, and guideline-recommended medications to lower glucose levels among patients with Medicare Advantage health insurance, particularly among patients who may benefit from preferential use of these medications, such as those with underlying cardiovascular or kidney disease. The effect of the observed disparities may be unknown until the long-term benefits of these agents are more definitively established. Initiation of GLP-1RA and SGLT2i treatment was also reduced among individuals in lower-income households, potentially contributing to poor health outcomes in this population. The findings suggest that innovative solutions are needed to address logistical and financial barriers to evidence-based diabetes management, including simplifying coverage requirements, reducing cost-sharing responsibilities, and creating transparent and straightforward avenues for all patients to obtain and afford the medications they need to optimally manage their disease. Such efforts may help improve access to new diabetes therapeutics, reduce disparities, and improve the health outcomes for patients living with diabetes.

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    Article Information

    Accepted for Publication: December 10, 2020.

    Published: February 1, 2021. doi:10.1001/jamanetworkopen.2020.35792

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 McCoy RG et al. JAMA Network Open.

    Corresponding Author: Rozalina G. McCoy, MD, MS, Division of Community Internal Medicine, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 (mccoy.rozalina@mayo.edu).

    Author Contributions: Dr McCoy had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: McCoy, Van Houten, Ross.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: McCoy.

    Critical revision of the manuscript for important intellectual content: Van Houten, Deng, Karaca-Mandic, Ross, Montori, Shah.

    Statistical analysis: Van Houten, Deng, Karaca-Mandic.

    Obtained funding: McCoy.

    Administrative, technical, or material support: Shah.

    Conflict of Interest Disclosures: Dr McCoy reported receiving a Quality Measure Innovation Grant from the AARP outside the submitted work. Dr Karaca-Mandic reported receiving grants from the American Cancer Society, receiving personal fees from Sempre Health and Precision Health Economics, serving as chief executive officer and co-founder of XanthosHealth LLC, and serving as advisor to Koya Medical, Inc, outside the submitted work. Dr Ross reported receiving grants from the US Food and Drug Administration (FDA), Johnson & Johnson, Medical Devices Innovation Consortium, the Agency for Healthcare Research and Quality (AHRQ), the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), the Laura and John Arnold Foundation, the Centers for Medicare & Medicaid Services, and Medtronic, Inc, outside the submitted work. Dr Shah reported receiving research support through Mayo Clinic from the FDA to establish the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation program, the Centers of Medicare & Medicaid Innovation under the Transforming Clinical Practice Initiative, the AHRQ, the NHLBI, NIH, the National Science Foundation, and the Patient Centered Outcomes Research Institute. No other disclosures were reported.

    Funding/Support: This study was supported by the grant K23DK114497 from the the National Institute of Diabetes and Digestive and Kidney Diseases, NIH (Dr McCoy), Comparative Health System Performance Initiative grant 1U19HS024075 from the AHRQ (Dr Shah), and grant R01HS025164 from the AHRQ (Dr Karaca-Mandic).

    Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Disclaimer: Study contents are the sole responsibility of the authors and do not necessarily represent the official views of the NIH.

    Meeting Presentation: This paper was presented at the virtual American Diabetes Association 80th Scientific Sessions; June 12, 2020.

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