FormalPara Key Summary Points

Why carry out this study?

Type 2 diabetes (T2D) is prevalent across all races and ethnic groups in the USA; however, the Hispanic/Latino population experience a disproportionately higher disease prevalence and worse outcomes compared with other groups.

Current guidelines for T2D management prioritize the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in certain populations as first-line injectable glucose-lowering therapy.

There are limited real-world studies assessing glycemic and cost outcomes among Hispanic/Latino adults with T2D using these injectable agents.

What was learned from the study?

In this real-world analysis, Hispanic/Latino patients initiating dulaglutide demonstrated greater glycated hemoglobin (HbA1c) reduction and achievement of 12 month follow-up HbA1c < 7.0%, compared with those who initiated basal insulin.

Follow-up all-cause total costs per 1% reduction in HbA1c were significantly lower in the dulaglutide cohort compared with the basal insulin cohort. Diabetes-related total costs per 1% reduction in HbA1c were numerically lower in the dulaglutide cohort compared with the basal insulin cohort.

These real-world results demonstrate that dulaglutide may be an effective therapeutic option for the vulnerable Hispanic/Latino population and may help with achieving improved T2D outcomes.

Introduction

Type 2 diabetes (T2D) is a chronic, progressive disease that affected an estimated 35.4 million adults in the USA in 2019 [1]. T2D risk varies across various racial and ethnic groups and a disproportionately higher prevalence has been observed among the Hispanic/Latino population (22.1%) compared with non-Hispanic/Latinos (12.1–20.4%) [2]. Research indicates that the etiology of higher T2D prevalence in the Hispanic/Latino population is likely owing to a combination of genetic, socioeconomic, and cultural factors [3,4,5,6]. Barriers to optimal glycemic management in Hispanic/Latino people with T2D are often rooted in inequitable access to healthcare resources, including lack of health insurance, financial and language barriers, and poor health literacy [7]. This results in adverse health outcomes, greater disease severity, and a substantial comorbidity burden on individuals and the healthcare system [4, 6, 8, 9]. According to the American Diabetes Association (ADA), care for people with diabetes, including direct medical costs and reduced productivity, amounted to $327 billion in 2017 [10].

People with T2D who do not achieve recommended glycemic targets may eventually require treatment intensification with insulin or a glucagon-like peptide-1 receptor agonist (GLP-1 RA), such as dulaglutide, or the gastric inhibitory peptide (GIP) and GLP-1 dual receptor agonist, tirzepatide [11]. Choice of glucose-lowering agents in T2D should be guided by clinical considerations (e.g., presence or high risk of cardiovascular disease, heart failure, chronic kidney disease, and hypoglycemia), side effect profiles of medications, contraindications, and individual preferences [12]. Although it is common practice to initiate insulin therapy with higher HbA1c levels, it is often linked to an increased risk of hypoglycemia and weight gain [13,14,15]. In contrast, GLP-1 RAs stimulate glucose-dependent insulin release while inhibiting glucagon secretion, and thereby minimize hypoglycemia risk, facilitate weight reduction, and achieve glucose reduction [15,16,17,18]. In the phase 3 clinical trials for dulaglutide (AWARD Program), once-weekly dulaglutide demonstrated effective glycemic and weight reduction benefits and a low incidence of hypoglycemia [19]. Current ADA/European Association for the Study of Diabetes (EASD) guidelines recommend the use of GLP-1 or GIP/GLP-1 receptor agonists in most individuals as first-line injectable glucose-lowering therapy before insulin [20, 21].

Real-world glycemic and cost outcomes in adults with T2D who initiated dulaglutide compared with those who initiated basal insulin have been assessed in the DISPEL (dulaglutide versus basal insulin injection naïve patients with type 2 diabetes: effectiveness in reaL world) study [22]. The study reported significantly greater glycated hemoglobin (HbA1c) reduction in adults with T2D who initiated dulaglutide compared with those who initiated basal insulin. Furthermore, the study also reported lower costs to achieve ≥ 1% HbA1c reduction among those who initiated dulaglutide versus basal insulin.

Despite guideline recommendations and their proven effectiveness in terms of glycemic management and reducing costs associated with T2D management, there is a notable underutilization of GLP-1 RAs in the Hispanic/Latino population relative to that of non-Hispanic ethnicity, even though the former reports a greater prevalence of T2D and related complications [23]. Investigating this disparity and its impact on clinical and economic outcomes can provide insights into equitable and effective treatment strategies for this specific demographic. Although individual studies have independently investigated the use of dulaglutide or basal insulin in the Hispanic/Latino population, none have directly compared these two injectable therapies within this specific demographic [24,25,26].

The aim of this study, which is an extension of the DISPEL study, was to examine glycemic outcomes, i.e., HbA1c levels post-treatment initiation, change in HbA1c from baseline, and cost outcomes, including costs per 1% HbA1c reduction over a 1-year period among the Hispanic/Latino population initiating dulaglutide or basal insulin for T2D management. To our knowledge, this is the first study comparing these real-world outcomes in the Hispanic/Latino population.

Methods

Study Design and Data Source

This study is an extension of the DISPEL study [22], and the methodologies presented below are similar to those presented in the DISPEL study.

This retrospective, observational, cohort study was conducted from July 2014 to March 2022 using data from the Optum Research Database (ORD). The ORD is a US-based claims database with linked enrollment from 1993 to present of more than 75 million people. Medical claims include multiple diagnosis codes recorded with the International Classification of Diseases, Ninth and Tenth Revisions (ICD-9 and ICD-10), Clinical Modification (CM) diagnosis codes; procedures recorded with ICD-9 and ICD-10-CM procedure codes, Current Procedural Terminology, or Healthcare Common Procedure Coding System codes; site of service codes; provider specialty codes; revenue codes for facilities; and paid amounts. Pharmacy claims data include National Drug Code, dosage form, drug strength, fill date, days of supply, and paid amounts. In addition, the database contains laboratory test results, such as HbA1c, and linked sociodemographic data, such as race/ethnicity and household income.

Study Sample and Cohorts

The study sample included a Hispanic/Latino population who were commercial or Medicare Advantage enrollees with at least one pharmacy claim for dulaglutide or basal insulin during the identification period, 1 January 2015 to 31 March 2021. The date of the first dulaglutide or basal insulin claim during the identification period was the index date, and the medication on the index date was the index therapy. Patients were included if they met the following criteria: age ≥ 18 years in the index year; continuous enrollment with medical and pharmacy benefits during the 6 month baseline and 12 month follow-up periods to ensure complete capture of patient healthcare activities; at least one T2D diagnosis code during baseline; and at least one HbA1c laboratory test result during baseline and from 4 to 12 months of follow-up. The identification and study periods were defined to allow a 6-month lag between the latest date of service and data extraction for complete adjudication of the medical and pharmacy claims. Excluded from the study were those who had diagnosis of type 1 diabetes and/or claims for injectable antihyperglycemic medications (insulin, GLP-1 RA, and pramlintide) at baseline; medical claims with diagnosis or procedure codes for secondary or gestational diabetes, pregnancy, labor, or delivery, bariatric surgery, or other procedures for morbid obesity at baseline or follow-up; pharmacy claims for both dulaglutide and basal insulin on the index date; missing or invalid demographic information; and anomalous HbA1c results. Eligible patients were assigned to cohorts on the basis of the index therapy, with propensity score matched on demographic and baseline characteristics.

Study Variables and Outcomes

Demographic characteristics included age, sex, US Census region, household net income range, insurance type, and index year. Clinical characteristics measured during baseline included comorbid conditions, Diabetes Complications Severity Index (DCSI) score [27], and continuous and categorical HbA1c values. Comorbid conditions included hypertension, hyperlipidemia, obesity, cardiovascular disease (congestive heart failure, ischemic heart disease, cardiac disease, and peripheral artery disease), and hypothyroidism; these were measured with at least two medical claims with relevant diagnosis codes at least 30 days apart or, in the case of hypertension and hyperlipidemia, at least one medical claim with a relevant diagnosis and at least one claim for a relevant medication was also captured. The primary outcomes were 12 month follow-up HbA1c, change in HbA1c from baseline to 12 month follow-up, and proportion of patients achieving the HbA1c target of < 7.0%. Secondary outcomes included all-cause and diabetes-related healthcare resource utilization (HCRU) and costs at 12 month follow-up. All-cause utilization was measured from all medical claims, irrespective of diagnosis codes. Diabetes-related utilization was measured from medical claims with diagnosis codes for diabetes in any position on the claim. Costs were adjusted using the annual medical care component of the consumer price index to reflect inflation between the date of the claim and 2021 [28] as well as for estimated coordination of benefits. Costs per 1% reduction in HbA1c were the sum of total all-cause or diabetes-related costs divided by the sum of change in HbA1c value and were measured across all patients by cohort at 12 month follow-up.

Statistical Analysis

Patients in each cohort were exact matched on baseline HbA1c categories < 7.0%, 7.0 to < 8.0%, 8.0 to < 9.0%, 9.0 to < 10.0%, and ≥ 10.0%. They were then propensity-score matched 1:1 without replacement on baseline demographic and clinical characteristics using logistic regression. Patients were considered matched if their propensity scores were within a caliper of 0.2 of the standard deviation of the logit [29]. The success of the match was evaluated by comparing all the baseline variables between cohorts using standardized difference <|10.0%|, variance ratios 0.5–2.0, and balanced propensity-score histograms [29]. Sub-group analyses were carried out for matched pairs of patients with 6 month HbA1c results and the measured values included 6-month follow-up HbA1c, HbA1c value 4–6 months after the index date and closest to 6 months, and change in HbA1c from baseline to 6 months. p-Values for differences in follow-up all-cause and diabetes-related total costs per 1% reduction in HbA1c between post-match cohorts were calculated with variance-stabilized bootstrap t-method using 5000 samples. The outcomes were compared between the matched cohorts using Student’s two-sided t-tests for continuous variables and chi-square statistics for binary and categorical variables. Statistical significance was defined as p < 0.05. Change in HbA1c and achievement of HbA1c < 7.0% at follow-up were modeled with ordinary least squares (OLS) regression and logistic regression, respectively, on the post-match sample, controlling for baseline continuous HbA1c. Follow-up diabetes-related total costs were estimated with a generalized linear model (GLM) with gamma distribution and log link controlling for continuous baseline diabetes-related total costs. Sensitivity analyses for the regressions were conducted by controlling for additional variables on which patients were not well matched after propensity-score matching, including age, index year, baseline all-cause office visit counts, baseline all-cause other medical costs, and household net income. All analyses were generated using SAS® software version 9.4 (2016; SAS Institute Inc., Cary, NC, US).

Compliance with Ethics Guidelines

All study data were accessed in compliance with US patient confidentiality requirements, including the Health Insurance Portability and Accountability Act (HIPAA) of 1996. As this study used only de-identified data compliant with the HIPAA from the ORD, it was exempt from institutional review board approval. The data supporting the study results were provided by Optum, Inc. and were used under license for this study.

Results

Baseline Characteristics

A total of 5388 patients were included in the initial prematch sample: 1892 (35.1%) in the dulaglutide cohort and 3496 (64.9%) in the basal insulin cohort. After propensity-score matching, each cohort consisted of 1436 patients (Supplementary Fig. 1). The propensity-score matched cohorts were well balanced on all demographic and baseline variables except age (standardized difference: −12.5%), index year (standardized differences: −51.9% to 30.2%), baseline all-cause office visit counts (standardized difference: −12.7%), and baseline all-cause other medical cost (standardized difference: −10.5%). The mean [standard deviation (SD)] age in the matched dulaglutide cohort was slightly less than that in the basal insulin cohort: 59.8 [12.8] and 61.4 [12.9] years, respectively (standardized difference: −2.5%; Table 1). Approximately half of the population was female (dulaglutide: 45.7%, basal insulin: 48.6%; standardized difference: −5.9%). A numerically higher proportion of the dulaglutide cohort were commercial insurance enrollees compared with the basal insulin cohort (52.8% and 48.8%, respectively); however, the standardized difference (8.0%) indicated that the post-matched cohorts were balanced on insurance type. The matched cohorts were balanced on clinical characteristics with standardized differences <|10.0%|. The mean [SD] DCSI score was 1.05 [1.45] in the dulaglutide cohort and 1.14 [1.45] in the basal insulin cohort (standardized difference: −6.4%). The most common comorbid conditions at baseline were hypertension (dulaglutide: 65.1%, basal insulin: 67.3%; standardized difference: −4.7%) and hyperlipidemia (dulaglutide: 64.5%, basal insulin: 68.3%; standardized difference: −8.0%; Table 1).

Table 1 Post-matching demographic and clinical characteristics
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Glycemic Outcomes

The dulaglutide cohort had a significantly lower mean (SD) 12 month follow-up HbA1c [7.71% (1.58)] compared with the basal insulin cohort [8.32% (1.75), p < 0.001; Fig. 1]. Similar results were observed at the 6 month follow-up for the 560 matched pairs of patients with 6 month HbA1c results (Supplementary Fig. 2). Patients initiating dulaglutide experienced a mean [SD] HbA1c reduction of 1.40% [1.88] from baseline to 12 month follow-up, compared with a 0.92% [2.07] reduction observed among patients initiating basal insulin (p < 0.001). Furthermore, a significantly higher proportion of patients in the dulaglutide cohort achieved glycemic management, i.e., HbA1c < 7.0%, compared with those in the basal insulin cohort (37.9% versus 22.1%, respectively; p < 0.001). The proportion of patients with follow-up HbA1c values ≥ 8.0% were lower in the dulaglutide cohort (all p < 0.05) versus the basal insulin cohort (Fig. 2). OLS regression of change in HbA1c and logistic regression of achievement of HbA1c < 7.0% mirrored these results. The dulaglutide cohort had a significantly larger improvement in HbA1c compared with the basal insulin cohort (estimate: −0.57; 95% confidence interval (CI) −0.68 to −0.45, p < 0.001; Fig. 1). Moreover, patients initiating dulaglutide displayed higher odds of achieving HbA1c < 7.0% compared with those initiating basal insulin (odds ratio: 2.19; 95% CI 1.85 −2.59, p < 0.001; Supplementary Table 1). In the sensitivity analyses, the additional covariates (age, index year, baseline all-cause office visit counts, baseline all-cause other medical costs, and household income) yielded comparable results (data not shown).

Fig. 1
figure 1

HbA1c at 12 month follow-up among patients initiating dulaglutide versus basal insulin. †Mean change in HbA1c from baseline to 12 months; ‡estimate obtained from OLS regression in post-match cohorts; p < 0.001 for change in HbA1c; HbA1c glycated hemoglobin; N cohort size; OLS ordinary least squares

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Fig. 2
figure 2

HbA1c distribution at baseline and 12 month follow-up among patients initiating dulaglutide versus basal insulin*. *Significant differences (p < 0.05) between the cohorts in each HbA1c category are represented by solid bars; non-significant differences are represented by patterned bars; HbA1c glycated hemoglobin

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Healthcare Costs and Healthcare Resource Utilization (HCRU)

At 12 months of follow-up, the matched dulaglutide cohort had significantly lower proportions of patients with ≥ 1 all-cause outpatient visits (52.0% versus 56.3%, respectively; p = 0.022), emergency room visits (28.3% versus 32.2%, respectively; p = 0.023), and inpatient stays (7.0% versus 11.4%, respectively; p < 0.001) compared with the basal insulin cohort (Table 2). Similar results were observed for the diabetes-related HCRU variables: diabetes-related outpatient visits (29.1% versus 36.4%), emergency room visits (17.0% versus 22.7%), and inpatient stays (6.7% versus 10.9%) for dulaglutide and basal insulin, respectively (p < 0.001 for all). The dulaglutide cohort had significantly higher mean all-cause ($11,428 versus $7979) and diabetes-related ($8745 versus $4866) pharmacy costs (both p < 0.001). The higher diabetes-related pharmacy costs drove higher mean diabetes-related total costs in the dulaglutide cohort ($13,620 versus $10,480; p < 0.001). All-cause total costs were numerically higher in the dulaglutide cohort, although the difference was not statistically significant ($19,258 versus $17,579; p = 0.121). The results of the GLM regression of follow-up diabetes-related total costs were consistent with the descriptive analysis. The dulaglutide cohort had 31% higher follow-up diabetes-related total costs compared with the basal insulin cohort (cost ratio: 1.31; 95% CI 1.17–1.47, p < 0.001). The predicted costs were $14,403 for the dulaglutide cohort and $10,994 for the basal insulin cohort (Supplementary Table 2). Results from the sensitivity analysis were similar (data not shown). The dulaglutide cohort had significantly lower all-cause total costs per 1% reduction in HbA1c compared with the basal insulin cohort ($13,768 versus $19,128; p < 0.001; Fig. 3). Diabetes-related costs per 1% reduction were numerically lower for the dulaglutide cohort, but the difference was not statistically significant ($9737 versus $11,403, respectively; p = 0.081).

Table 2 Healthcare costs1 and healthcare resource utilization at 12 month follow-up among patients initiating dulaglutide versus basal insulin
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Fig. 3
figure 3

Healthcare costs;† at 12 month follow-up per 1% reduction in HbA1c among patients initiating dulaglutide versus basal insulin, †costs were adjusted using the annual medical care component of the Consumer Price Index to reflect inflation to year 2021 and for estimated coordination of benefit, *p-values and bias-corrected CIs (represented by error bars) were obtained from a variance-stabilized bootstrap t-method using 5000 samples, HbA1c glycated hemoglobin, $ US dollars, N cohort size, CI confidence interval

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Discussion

This retrospective analysis of administrative claims data evaluated glycemic and cost outcomes among Hispanic/Latino people with T2D in the USA initiating dulaglutide versus basal insulin. The results of this real-world analysis demonstrated that treatment with dulaglutide was associated with a greater mean HbA1c reduction from baseline to 6 and 12 months follow-up and lower all-cause costs to achieve ≥ 1% reduction compared with basal insulin.

Our findings in the Hispanic/Latino population are consistent with results obtained from the broader population as well as controlled clinical trials. A post hoc analysis of six phase 3 AWARD studies assessing the efficacy and safety of once weekly dulaglutide in the Hispanic/Latino population found that dulaglutide improved glycemic management and was associated with low hypoglycemia risk when used without insulin [24]. Another post hoc analysis of the AWARD-2 trial in adults with T2D demonstrated greater reductions in HbA1c with dulaglutide versus insulin glargine [30]. Similar results were reported in a meta-analysis of studies comparing GLP-1 RAs with basal insulin [18]. More recently, the DISPEL study compared real-world outcomes among initiators of dulaglutide and basal insulin [22]. The authors reported improved glycemic outcomes in the dulaglutide cohort compared with the basal insulin cohort in terms of greater reductions in HbA1c (1.12% versus 0.51%, p < 0.001) and higher proportions of patients with 12 month follow-up HbA1c < 7.0% (42.5% versus 25.0%, p < 0.001). The current study reported comparable results for both parameters (mean HbA1c reduction: 1.40% versus 0.92%, p < 0.001; proportions of patients with 12 month follow-up HbA1c < 7.0%: 37.9% versus 22.1%, p < 0.001), suggesting greater glycemic management with dulaglutide compared with basal insulin and reinforcing the applicability of dulaglutide treatment in the Hispanic/Latino population.

In addition to clinical success, the cost-effectiveness of any treatment plays a pivotal role in treatment selection. In a real-world cost-effectiveness analysis, Yang et al. concluded that higher pharmacy and outpatient costs associated with GLP-1 RA use compared with insulin therapy were offset by a reduction in expenses related to emergency room visits and inpatient admissions. This was attributed to the reduced risks of all-cause mortality and hypoglycemia associated with GLP-1 RA use [31]. Similar findings were observed in two cost-utility analyses of dulaglutide versus insulin glargine [32, 33]. In both studies, dulaglutide was shown to be a cost-effective treatment option for T2D, despite higher annual costs, mainly attributable to pharmacy costs. Consistent with the previous results, the present study reported higher mean pharmacy costs for patients initiating dulaglutide compared with those initiating basal insulin. Similar results were seen in the earlier DISPEL study among a subset of patients with complete cost data. However, the current study observed less consistency in total diabetes-related costs, which were significantly higher in the dulaglutide cohort in this Hispanic/Latino population but not significantly different between cohorts in the DISPEL study. To combine clinical effectiveness results with cost outcomes, costs per 1% HbA1c reduction were estimated. In the DISPEL study, the dulaglutide cohort had significantly lower total all-cause and diabetes-related costs per 1% HbA1c reduction. However. in this study, differences between cohorts in diabetes-related costs per 1% HbA1c reduction were not statistically significant. This raises important questions regarding T2D treatment among Hispanic/Latino individuals, such as physician prescribing preferences and therapy adherence, which may be pursued in future research.

Emerging evidence suggests that people from racial/ethnic minority groups consistently have inequitable access to guideline-recommended therapeutics that improve disease burden and quality of life [34]. For Hispanic/Latino people with T2D, these disparities often manifest as barriers to optimal glycemic management and adherence, consequently impacting treatment outcomes. In this context, the results of the current study suggest that treatment with GLP-1 RAs, such as dulaglutide, should be considered as preferred treatment over basal insulin. Further research is warranted to explore the long-term outcomes and cost-effectiveness of these injectable therapies in this vulnerable population.

We acknowledge certain limitations of our study. As with all real-world evidence studies using claims data, there might be potential misclassification of disease, severity status, or other outcomes. The study sample comprised Hispanic/Latino patients who were identified using a non-patient-reported race/ethnicity identifier. Therefore, some of the patients may have been misclassified as Hispanic/Latino. Moreover, the analysis was limited to commercial and Medicare Advantage enrollees, consequently limiting the generalizability of the results to individuals who are uninsured, fee-for-service Medicare beneficiaries, or those residing in institutions such as nursing homes. This may be especially true for this Hispanic/Latino sample: the Census Bureau reported that 17.7% of civilian non-institutionalized Hispanic/Latino individuals in the USA did not have health insurance coverage in 2021 compared with 5.7% of white non-Hispanic/Latino individuals. A higher percentage of Hispanic/Latino individuals had public insurance compared with their non-Hispanic/Latino counterparts [35]. Lastly, the matched dulaglutide and basal insulin patients were not representative of the initial dulaglutide and basal insulin cohorts. In analysis of matched versus unmatched patients within index therapy cohort (data not shown), the matched dulaglutide patients were more likely than the unmatched dulaglutide patients to have more severe and less well-controlled T2D, while matched versus unmatched basal insulin patients were more likely to have less severe and better-controlled T2D. This also limits the generalizability of our results.

Conclusions

In this real-world analysis, Hispanic/Latino people with T2D who initiated dulaglutide demonstrated greater HbA1c reduction and achievement of 12 month follow-up HbA1c < 7.0%, compared with those who initiated basal insulin. All-cause total costs per 1% reduction in HbA1c were also significantly lower in dulaglutide initiators compared with basal insulin initiators. Although diabetes-related total cost was numerically lower with dulaglutide, this difference was not statistically significant. By demonstrating improved glycemic management and cost-effectiveness per 1% HbA1c reduction, the findings from this analysis indicate that dulaglutide may be a viable therapeutic option for an injection-naïve Hispanic/Latino population and may help achieve improved T2D outcomes. Consequently, our study results echo diabetes guideline recommendations, reinforcing the potential benefits of using GLP-1 RAs over insulin as first-line injectable glucose-lowering therapy in people with T2D.