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      Cost-Effectiveness of SGLT2 Inhibitors in a Real-World Population: A MICADO Model-Based Analysis Using Routine Data from a GP Registry

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          Abstract

          Objective

          Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have been shown to reduce the risk of cardiovascular complications, which largely drive diabetes’ health and economic burdens. Trial results indicated that SGLT2i are cost effective. However, these findings may not be generalizable to the real-world target population. This study aims to evaluate the cost effectiveness of SGLT2i in a routine care type 2 diabetes population that meets Dutch reimbursement criteria using the MICADO model.

          Methods

          Individuals from the Hoorn Diabetes Care System cohort ( N = 15,392) were filtered to satisfy trial inclusion criteria (including EMPA-REG, CANVAS, and DECLARE-TIMI58) or satisfy the current Dutch reimbursement criteria for SGLT2i. We validated a health economic model (MICADO) by comparing simulated and observed outcomes regarding the relative risks of events in the intervention and comparator arm from three trials, and used the validated model to evaluate the long-term health outcomes using the filtered cohorts’ baseline characteristics and treatment effects from trials and a review of observational studies. The incremental cost-effectiveness ratio (ICER) of SGLT2i, compared with care-as-usual, was assessed from a third-party payer perspective, measured in euros (2021 price level), using a discount rate of 4% for costs and 1.5% for effects.

          Results

          From Dutch individuals with diabetes in routine care, 15.8% qualify for the current Dutch reimbursement criteria for SGLT2i. Their characteristics were significantly different (lower HbA1c, higher age, and generally more preexisting complications) than trial populations. After validating the MICADO model, we found that lifetime ICERs of SGLT2i, when compared with usual care, were favorable (< €20,000/QALY) for all filtered cohorts, resulting in an ICER of €5440/QALY using trial-based treatment effect estimates in reimbursed population. Several pragmatic scenarios were tested, the ICERs remained favorable.

          Conclusions

          Although the Dutch reimbursement indications led to a target group that deviates from trial populations, SGLT2i are likely to be cost effective when compared with usual care.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40273-023-01286-3.

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          Most cited references52

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          Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

          The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.
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            Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

            Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754 , respectively.).
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              Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes

              The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined.
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                Author and article information

                Contributors
                li.xinyu@rug.nl
                Journal
                Pharmacoeconomics
                Pharmacoeconomics
                Pharmacoeconomics
                Springer International Publishing (Cham )
                1170-7690
                1179-2027
                10 June 2023
                10 June 2023
                2023
                : 41
                : 10
                : 1249-1262
                Affiliations
                [1 ]GRID grid.4830.f, ISNI 0000 0004 0407 1981, University of Groningen, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, ; A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
                [2 ]GRID grid.31147.30, ISNI 0000 0001 2208 0118, Expertise Center for Methodology and Information Services, , National Institute for Public Health and the Environment, ; Bilthoven, The Netherlands
                [3 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Department of Health Sciences, Faculty of Science, Amsterdam Public Health Research Institute, , Vrije Universiteit Amsterdam, ; Amsterdam, The Netherlands
                [4 ]Zorginstituut Nederland, Diemen, The Netherlands
                [5 ]GRID grid.6906.9, ISNI 0000000092621349, Erasmus School of Health Policy & Management, , Erasmus University Rotterdam, ; Rotterdam, The Netherlands
                [6 ]GRID grid.5477.1, ISNI 0000000120346234, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, , Utrecht University, ; Utrecht, The Netherlands
                [7 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Department of Epidemiology and Data Sciences, Amsterdam University Medical Center, , Location Vrije Universiteit, ; Amsterdam, The Netherlands
                [8 ]Amsterdam Public Health, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
                [9 ]GRID grid.5477.1, ISNI 0000000120346234, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, , Utrecht University, ; Utrecht, The Netherlands
                [10 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Department of General Practice, Amsterdam University Medical Center, , Location Vrije Universiteit, ; Amsterdam, The Netherlands
                [11 ]GRID grid.31147.30, ISNI 0000 0001 2208 0118, Center for Nutrition, Prevention and Health Services Research, , National Institute for Public Health and the Environment, ; Bilthoven, The Netherlands
                Author information
                http://orcid.org/0000-0002-0225-6937
                http://orcid.org/0000-0002-6341-7976
                http://orcid.org/0000-0003-3550-990X
                http://orcid.org/0000-0001-5157-5355
                http://orcid.org/0000-0002-4181-0937
                http://orcid.org/0000-0002-5907-7219
                http://orcid.org/0000-0002-3679-9710
                http://orcid.org/0000-0003-4521-9500
                http://orcid.org/0000-0002-5788-0454
                Article
                1286
                10.1007/s40273-023-01286-3
                10492753
                37300652
                f65b808d-4cec-4131-ba44-8c31d19e342f
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 21 May 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100010763, Zorginstituut Nederland;
                Categories
                Original Research Article
                Custom metadata
                © Springer Nature Switzerland AG 2023

                Economics of health & social care
                Economics of health & social care

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