Zum Inhalt springen
Sponsorship
Die MVF-Knowledge-HubsFrisch aus der Forschung. Täglich aktualisiert!

Suchen Sie in Hunderten nationaler und internationaler Datenbanken nach dem neuesten Studienwissen der angegebenen Themengebiete und/oder lassen Sie sich werktäglich per Newsletter informieren. Die Newsfeeds werden auf deutsch übersetzt and nach Übertragbarkeit auf das deutsche Gesundheits-/Versorgungssystem ausgewählt:

Zu den Knowledge-Hubs

Top original article

Cite Download PDF TXT - Download CC BY 4.0

Comparison of healthcare costs of type 2 diabetics using empagliflozin, DPP-4 inhibitors and GLP-1 agonists (Print)

Dr. rer. pole. Marco Penske / Prof. Dr. med. Jens Aberle / Dr. rer. nat. Barthold Deiters MHA / Prof. Dr. rer. oec. Thomas Wilke

According to the National Care Guideline (NVL) for the treatment of T2DM, the use of various antidiabetic therapies should be gradual if patients are unable to achieve their individual therapy goals through lifestyle changes, e.g. B. by changing your eating habits and increasing physical activity.3 Known risk factors such as previous cardiovascular and renal diseases should also be taken into account when making individual treatment decisions. The combination of metformin with an SGLT-2 inhibitor (SGLT-2i) or a GLP-1 receptor agonist (GLP-1-RA) is recommended, for example, for patients who already have clinically relevant cardiovascular disease (CVD ).4 Furthermore, dipeptidyl peptidase-4 inhibitors (DPP-4i) in addition to metformin represent another treatment alternative for lowering blood sugar, but did not show significant benefits in reducing cardiovascular events. Cardiovascular diseases cause the highest expenditure in the German healthcare system and are responsible for up to 50% of the treatment costs of patients with T2DM due to the frequently required hospital stays.5 The present healthcare research study compares the direct healthcare costs of T2DM patients who receive treatment with the SGLT -2 inhibitor empagliflozin (EMPA) started with patients treated for the first time with DPP-4i or GLP-1-RA from the perspective of the statutory health insurance in Germany.

Read more
First publication date: 28.11.2022
Dr. rer. pol. Marco PenskeDr. rer. pole. Marco PenskeProf. Dr. med. Jens AberleProf. Dr. med. Jens AberleDr. rer. nat. Barthold Deiters MHADr. rer. nat. Barthold Deiters MHAProf. Dr. rer. oec. Thomas WilkeProf. Dr. rer. oec. Thomas Wilke

DOI

http://doi.org/10.24945/MVF.06.22.1866-0533.2465

Downloads

Full article as PDF
Plain text as TXT

Abstract: Vergleich der Gesundheitskosten von Typ-2 Diabetikern bei der Anwendung von Empagliflozin, DPP-4-Hemmern und GLP-1-Agonisten (Print)

Study objective: The present GKV routine data analysis compares direct healthcare costs of patients with type 2 diabetes mellitus (T2DM) who received treatment with empagliflozin (EMPA) versus dipeptidyl peptidase-4 inhibitors (DPP-4) and EMPA versus GLP1 receptor agonists ( GLP-1-RA).Methodology: Patients with at least two outpatient diagnoses and/or one inpatient diagnosis of type 2 diabetes mellitus (T2DM), who were continuously insured in the period 2014-2018 and were treated with EMPA, DPP-4 or GLP-1-RA began were analyzed retrospectively. Healthcare costs were assessed from the start of therapy to the end of data availability, death, or end of therapy. Depending on the concomitant medication prescribed at the start of therapy, patients were assigned to four different, partially overlapping subgroups: (1) monotherapy, (2) with insulin, (3) without insulin or (4) dual therapy with metformin. The cost comparisons were carried out on the basis of patient cohorts using propensity score matching (PSM). Results: Of the 24,465 patients included, 3,285 received EMPA, 19,443 DPP-4i and 1,747 GLP-1-RA. After adjustment using PSM, 298/49 patients with monotherapy, 823/583 with additional insulin therapy, 2,236/577 insulin-naïve patients and 1,430/376 patients with metformin dual therapy were compared between EMPA and DPP-4i or GLP-1-RA . The total costs after starting treatment with DPP-4i (or GLP-1-RA) were on average 7,009 euros (6,851 euros) compared to 4,274 euros (4,895 euros) for EMPA (p < 0.001). These results were consistent in all subgroup comparisons considered. Conclusion: Treatment with EMPA was associated with significantly lower healthcare costs (total treatment costs) over the course of therapy. The basis for the observed cost savings are the pleiotropic effects of EMPA, ie the effect on different organ systems or in different indication areas.

Abstract: Healthcare Resource Utilization and Associated Costs in New Users of Empagliflozin versus DPP-4 Inhibitors and GLP-1 Agonists

Purpose: This German claims data study aimed to compare direct healthcare costs in type 2 diabetes mellitus (T2DM) patients treated with empagliflozin (EMPA) compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) and EMPA compared to glucagon-like peptide-1 receptor agonists (GLP-1-RA). Methods: Continuously insured persons with at least two outpatient diagnoses and/or one inpatient diagnosis of T2DM were retrospectively evaluated, if they started a therapy with EMPA, DPP-4i, or GLP-1-RA in 2015-2018. Depending on the concomitant medication prescribed at therapy start, patients were assigned to four non-mutually exclusive groups: (1) monotherapy, (2) with insulin, (3) without insulin, or (4) dual therapy with metformin. Healthcare costs were assessed from therapy start until the end of data availability, death, or therapy discontinuation of index therapy, and were compared among propensity score-matched cohorts. Results: Of 24,465 patients included, 3,285 started a treatment with EMPA, 19,443 DPP-4i, and 1,747 GLP-1-RA. After pairwise PS matching, 298/49 patients with monotherapy, 823/583 with additional insulin therapy, 2,236/577 insulin-naive, 1,430/376 patients with metformin dual therapy were compared between EMPA and DPP-4 and GLP-1-RA, respectively. Mean total costs after start of DPP-4i were Euro 7.009 versus Euro 4.274 for EMPA (p < 0.001). Costs associated with GLP-1-RA treatment were also significantly higher compared with EMPA (Euro 6.851 versus Euro 4.895; p < 0.001). These results were mainly due to differences in inpatient costs and were consistent across all subgroup comparisons evaluated. Conclusion: Patients who started EMPA therapy had significantly lower healthcare costs over the course of treatment than patients who started DPP-4i and GLP-1-RA. The observed cost savings are based on the pleiotropic effects of EMPA, ie, its impact on different organ systems and in different indications, respectively.

Keywords (English)

antidiabetic drugs, DPP-4 inhibitors, GLP-1 receptor agonists, health care costs, SGLT2 inhibitors, Type 2 diabetes mellitus

Literature

1. Heidemann C, Scheidt-Nave C. Prevalence, incidence and mortality of diabetes mellitus in adults in Germany. J Heal Monit. 2017;2(3):98-121. Accessed September 10, 2021. https://www.mendeley.com/catalogue/2a75faed-bd43-324e-b7d2-4a8c6bf99fd4/?utm_source=desktop&utm_medium=1.19.4&utm_campaign=open_catalog&userDocumentId=f80f92c8-58b6-3d26 -8c35-fc5b86160c57 2. Tönnies T, Röckl S, Hoyer A, et al. Projected number of people diagnosed with Type 2 diabetes in Germany in 2040. Diabet Med. 2019;36(10):1217-1225. doi:10.1111/dme.13902 3. National Association of Statutory Health Insurance Physicians B. Carrier: National Care Guideline Type 2 Diabetes Partial publication of the long version 2nd edition, version 1. Published online 2021. Accessed July 6, 2021. www.leitlinien.de 4. Nespoux J, Vallon V. Renal effects of SGLT2 inhibitors: an update. Curr Opin Nephrol Hypertens. 2020;29(2):190. doi:10.1097/MNH.0000000000000584 5. Einarson TR, Acs A, Ludwig C, Panton UH. Economic Burden of Cardiovascular Disease in Type 2 Diabetes: A Systematic Review. Value Heal. 2018;21(7):881-890. doi:10.1016/J.JVAL.2017.12.019 6. Bang H, Tsiatis A. Estimating medical costs with censored data. Biometrics. 2000;87(2):329-343. doi:10.1093/BIOMET/87.2.329 7. Chen S, Rolfes J, Zhao H. Estimation of mean health care costs and incremental cost-effectiveness ratios with possibly censored data. Stata J. 2015;15(3):698-711. 8. Wilke T, Picker N, Müller S, Stürmlinger A, Deiters B, Dittmar A, Aberle J, Gabler M. Healthcare Resource Utilization and Associated Costs in New Users of Empagliflozin versus DPP-4 Inhibitors and GLP-1 Agonists: A Comparative Analysis Based on Retrospective Real-World Data from German Sickness Funds. Clinicoecon Outcomes Res. 2022 May 2;14:319-332. doi: 10.2147/CEOR.S357540. 9. Gabler M, Picker N, Müller S, Stürmlinger A, Deiters B, Dittmar A, Aberle J, Wilke T. Healthcare resource utilization and associated costs in new users of empagliflozin versus DPP-4 inhibitors and GLP-1 agonists: A retrospective cohort study based on real-world data from German sickness funds. Lecture at the congress of the German Society for Health Economics (dggö) 2022, lecture session “Economics of the pharmaceutical market”, March 28, 2022, abstract available at https://www.dggoe.de/conferences/2022/programm/21/session/66.10 . Ramos M, Foos V, Ustyugova A, Hau N, Gandhi P, Lamotte M. Cost-Effectiveness Analysis of Empagliflozin in Comparison to Sitagliptin and Saxagliptin Based on Cardiovascular Outcome Trials in Patients with Type 2 Diabetes and Established Cardiovascular Disease. Diabetes Ther. 2019;10(6):2153. doi:10.1007/S13300-019-00701-311. Kansal A, Reifsnider OS, Proskorovsky I, et al. Cost-effectiveness analysis of empagliflozin treatment in people with Type 2 diabetes and established cardiovascular disease in the EMPA-REG OUTCOME trial. Diabet Med. 2019;36(11):1494. doi:10.1111/DME.1407612. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015;373(22):2117-2128. doi:10.1056/NEJMoa150472013. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomized placebo-controlled trial. Lancet. 2019;394(10193):121-130. doi:10.1016/S0140-6736(19)31149-314. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. Drug Ther Bull. 2016;54(9):101. doi:10.1056/nejmoa160382715. Pantuzza LL, Ceccato M das GB, Silveira MR, Junqueira LMR, Reis AMM. Association between medication regimen complexity and pharmacotherapy adherence: a systematic review. Eur J Clin Pharmacol 2017 7311. 2017;73(11):1475-1489. doi:10.1007/S00228-017-2315-216. Komajda M, Anker SD, Cowie MR, et al. Physicians' adherence to guideline-recommended medications in heart failure with reduced ejection fraction: data from the QUALIFY global survey. Your J Heart Fail. 2016;18(5):514-522. doi:10.1002/EJHF.510 

Additional Information

Citation: Wilke et al.: “Comparison of the healthcare costs of type 2 diabetics when using empagliflozin, DPP-4 inhibitors and GLP-1 agonists”, in: “Monitor Healthcare Research” (06/22), pp. 68-73 . http://doi.org/10.24945/MVF.06.22.1866-0533.2465

Plain Text

Comparison of healthcare costs of type 2 diabetics using empagliflozin, DPP-4 inhibitors and GLP-1 agonists

According to the National Care Guideline (NVL) for the treatment of T2DM, the use of various antidiabetic therapies should be gradual if patients are unable to achieve their individual therapy goals through lifestyle changes, e.g. B. by changing your eating habits and increasing physical activity.3 Known risk factors such as previous cardiovascular and renal diseases should also be taken into account when making individual treatment decisions. The combination of metformin with an SGLT-2 inhibitor (SGLT-2i) or a GLP-1 receptor agonist (GLP-1-RA) is recommended, for example, for patients who already have clinically relevant cardiovascular disease (CVD ).4 Furthermore, dipeptidyl peptidase-4 inhibitors (DPP-4i) in addition to metformin represent another treatment alternative for lowering blood sugar, but did not show significant benefits in reducing cardiovascular events. Cardiovascular diseases cause the highest expenditure in the German healthcare system and are responsible for up to 50% of the treatment costs of patients with T2DM due to the frequently required hospital stays.5 The present healthcare research study compares the direct healthcare costs of T2DM patients who receive treatment with the SGLT -2 inhibitor empagliflozin (EMPA) started with patients treated for the first time with DPP-4i or GLP-1-RA from the perspective of the statutory health insurance in Germany.

>> This routine data analysis used an anonymized data set from GWQ ServicePlus AG, which includes health insurance data from more than 4 million GKV insured people from all over Germany. Over a five-year study period, a retrospective longitudinal analysis of the service costs incurred for outpatient care, hospital treatment and medication was carried out based on the costs documented in the database. The sample considered included all adults who were continuously insured between January 1, 2014 and December 31, 2018 (excluding deaths) and at least one outpatient prescription with EMPA, DPP-4i or GLP between January 1, 2015 and December 31, 2018. 1-RA received. Patients with T2DM were identified as such if at least one inpatient diagnosis or at least two outpatient diagnoses of T2DM (ICD-10: E11) were documented in two different quarters within one year before the start of treatment (index day). Patients who were diagnosed with another form of diabetes, malignant neoplasms or one of the three most costly morbidity groups (sepsis, HIV or opportunistic infections) according to the Federal Insurance Office in the 12 months before the start of treatment were excluded from the analysis. The patient-specific observation period ended with discontinuation of therapy (90-day therapy gap), death or on December 31, 2018 (end of data availability).
In order to compensate for structural differences in the patient characteristics between the comparison groups (Table 1) and thus to keep the risk of bias in this non-randomized research design as low as possible, the study cohorts were selected using the propensity score (PS) method (“1:1 matching”, Caliper ≤ 0.001) was preselected in such a way that only comparison groups whose characteristics were similar at the start of observation were compared with regard to the costs incurred during the course of therapy. This adjustment primarily took into account characteristics that were expected to have a connection with the treatment costs incurred. The propensity scores, i.e. the probability with which a patient will receive the therapy being compared (EMPA in comparison with DPP-4i or GLP-1-RA), was determined using logistic regression models, which take into account differences in demographics (age, Gender), morbidity (measured by the Charlson comorbidity index, level of care, and documented previous illnesses), previous cardiovascular and anti-diabetic medication, as well as previous healthcare expenditure one year before the start of therapy. In addition, for each comparison, additional subgroups were considered depending on the initiated antidiabetic treatment regimen ((1) monotherapy, (2) with insulin, (3) without insulin, or (4) dual therapy with metformin); Multiple assignment of patients to these groups was possible depending on the antidiabetic concomitant medication.
To determine the average cost per patient, a consistent estimator based on the inverse probability weighting for censoring subject (i) at time (FORMULA see PDF) according to the Kaplan-Meier method was used:

(FORMULA see PDF)

where Mi describes the total costs observable for the subject. The method, first described by Bang and Tsiatis, is based on the idea that each complete cost statement represents a total number
(FORMULA see PDF)

represents observations that could have been observed. When ∆ = 1, Xi = Ti, that is, the observed cost Mi is equal to the true cost.6,7

Results

A total of 24,465 T2DM patients newly treated with EMPA (n = 3,285), DPP-4i (n = 19,433) or GLP-1-RA (n = 1,747) were included in the study (Figure 1). Table 1 shows the baseline characteristics of these study cohorts. Differences in observable patient characteristics, such as: B. age at start of therapy, gender or comorbidities, could be balanced for the PS-adjusted comparison cohorts.
However, for the subgroup comparisons considered, an adjustment of the characteristics at the start of observation based on the PSM procedure was only possible to a limited extent due to the small sample size. Particularly for monotherapy, the number of patients included was too small to form robust comparison cohorts. Only about 8 - 12% of the patients started treatment with EMPA (n = 339) or DPP-4i (n = 2,286) or GLP-1-RA (n = 135) without concomitant antidiabetic medication. The proportion of insulin-naïve and insulin-experienced patients differed significantly between the comparison groups. More than half of the GLP-1-RA patients (50.7%; n = 885) were already on insulin at the start of therapy, while this proportion was the same for DDP-4i (17.2%; n = 3,349) and EMPA (30.8%; n = 1,013) was significantly lower. The dual combination of metformin and another antidiabetic drug recommended in the national care guidelines (NVL) for T2DM (SGLT2 inhibitors or GLP-1-RA are prioritized) was also used with varying frequency. While the proportion of patients treated in this way was highest in the EMPA group (46.5%; n = 1,526), only about a third (34.9%; n = 610) of the GLP-1-RA patients received the therapy in combination with metformin. Among patients who started treatment with DDP-4i, the proportion of metformin users at the time of therapy initiation was lowest (28.6%; n = 5,558).
Compared with EMPA, patients treated with DPP-4i (mean [mean]: 7,009 euros versus 4,274 euros) and GLP-1-RA (mean: 6,851 euros versus 4,895 euros) had significantly higher healthcare expenditures.8, 9 The largest differences between EMPA and DPP-4i were observed in inpatient treatment costs (mean: 1,455 euros versus 3,040 euros; p < 0.001), while cost differences compared to GLP-1-RA were primarily due to the expenditure on outpatient prescribed drugs (mean : 2,433 euros versus 3,575 euros; p < 0.001), as can be seen in Figure 2. Figure 3 summarizes the cost differences between the PS-adjusted study cohorts for the predefined subgroup analyses. Regardless of the comedication received, there was a clear cost advantage for EMPA in all comparison groups.
These differences were most pronounced when considering monotherapy. It is also notable that patients receiving dual combination with metformin and insulin-naïve patients tended to have lower healthcare expenditures than patients treated with insulin-free monotherapy.
In the latter group, the proportion of inpatient treatment costs and their absolute value were also significantly higher. However, most of the costs were incurred by patients who received insulin therapy - with correspondingly high drug costs.

discussion

The present retrospective analysis of GKV routine data shows savings potential in the treatment of patients with T2DM in Germany. Compared with the SGLT-2 inhibitor EMPA, treatment with DPP-4i and GLP-1-RA resulted in significantly higher direct healthcare expenditure on average, regardless of the antidiabetic comedication received. In particular, the significantly higher hospital costs for DPP4i patients are clear.
indicate clinical advantages of EMPA over DPP-4i and underline the results of clinical studies to reduce serious cardiovascular events requiring hospitalization.10,11 For example, in the cardiovascular outcome study “EMPA-REG OUTCOME” there was a significant reduction in the proportion observed in patients hospitalized due to heart failure due to EMPA.12 However, no significant differences were observed in inpatient expenditure for patients treated with EMPA or GLP-1-RA. This is not surprising since individual GLP-1 agonists such as liraglutide and dulaglutide have already been shown to have an advantage in reducing cardiovascular events in placebo-controlled outcome studies.13,14
The cost advantages of therapy with EMPA compared to GLP-1-RA were mainly reflected in drug costs and are therefore primarily due to direct price differences between the active ingredients. However, it should be noted that the study presented here calculated the drug costs based on the list prices documented in the database, to the extent that health insurance-specific discount agreements could not be depicted. It should also be noted that the cost calculation is based on the historical price level at the time the service is provided. Given the imminent patent expiry of various DPP-4i, drug costs may change in the future, particularly in this group.
DPP-4i, SGLT-2i, and GLP-1-RA were all originally developed as agents for the treatment of T2DM. While the DPP-4i remained in the indication area of T2DM, the GLP-1-RA were also tested for use in weight regulation in clinical studies and approved by the European Medicines Agency (EMA). The SGLT-2i, in turn, were also developed as medications for chronic heart failure and chronic kidney disease and some have already been approved. As of the end of 2020, antidiabetics had (also) become cardiovascular medications. The basis for this variety of indications for SGLT-2i were the pleiotropic effects of this class of active ingredients first observed in “EMPA-REG OUTCOME”.12
In pharmacology, pleiotropy refers to the presence of multiple effects for a single active ingredient. Due to its mechanism of action, EMPA shows pleiotropic effects, which, in addition to the blood sugar-lowering effect, include nephroprotection, the improvement of endothelial function, the blood pressure-lowering effect and the reduction of body weight. Through these favorable renal and metabolic effects, EMPA offers patients with heart failure and diabetes mellitus, especially those with chronic kidney failure as a comorbidity, a cross-indication therapeutic approach with which several diseases can be positively influenced at the same time.15 In addition, other active ingredients can be discontinued or their dosage reduced if necessary and thus tolerability can be improved. An improvement in adherence can also be achieved by reducing polypharmacy and simplifying therapy.16
In the present cost comparison study, the pleiotropic effects of EMPA were evident in the following endpoints:
• Reduction in the rate of overall hospitalizations compared to DPP-4 inhibitors and GLP-1 analogues by more than 20% each
• Halving the rate of heart failure hospitalizations compared to DPP-4 inhibitors and GLP-1 analogues
• Reduction of hospital treatment costs compared to DPP-4 inhibitors by more than half.

The present routine data analysis is based on a Germany-wide, representative data set and is therefore free of center- or patient-related selection bias. In addition, costs and resource consumption (healthcare resource utilization, HCRU) are reliably depicted in such data sets. However, some methodological limitations must be taken into account when interpreting the results. Although the comparability between the study cohorts was largely guaranteed using the PSM method, this only applies to patient characteristics observable in the data set, which can only be traced back to billing-relevant information from the health insurance companies.
Other clinical characteristics such as body weight, blood pressure or cholesterol levels are not shown because they are not directly relevant to billing. The adjustment of the blood sugar level at the start of therapy could not be recorded and was therefore not taken into account. In addition, the study cohorts considered differ quite significantly in the length of the available observation period, which is due, among other things, to the fact that EMPA has only been approved in Europe since 2014, while GLP-1-RA and DPP-4i have been in use since 2006/2007 Germany are available. Furthermore, there were no significant differences between the study cohorts with regard to treatment persistence.

Conclusion

Our analysis shows that T2DM patients receiving empagliflozin (EMPA) therapy incur, on average, fewer direct costs over the course of treatment than patients treated with DPP-4i and GLP-1-RA. Specifically, patients initially initiated on EMPA incurred lower inpatient costs than DPP-4i users, primarily due to lower rates of cardiovascular disease-related hospitalizations. The basis for the cost savings observed in this study are the pleiotropic effects of EMPA, ie the effect on different organ systems or in different indication areas, which offer further potential for savings, especially after approval for the treatment of heart failure.
The results of this study suggest that treatment with EMPA is a cost-effective option compared to DDP-4i, which is commonly prescribed in Germany, despite the higher drug price. Compared to GLP-1-RA, EMPA is at least equivalent in terms of costs and resource consumption and is even superior in a number of parameters. Further observational studies are recommended to validate these results in real care practice, especially with regard to possible long-term effects. <<

background

Diabetes mellitus continues to represent a significant burden on national health systems, both because of the high prevalence of this disease and the associated health and financial burdens. In Germany, according to current estimates based on data from the statutory health insurance (GKV), around 9.9% of the population suffer from diabetes.1 Patients with type 2 diabetes mellitus (T2DM) make up the largest proportion, with an estimated prevalence of 6 .9 million cases in 2015. Due to the aging of the population, the number will continue to rise by 2040, so that around 10.7 - 12.3 million people in Germany will suffer from diabetes.2

Do you want to leave us already?

Subscribe to our newsletter quickly. Then you can be sure that you won't miss anything.