A systematic review of the cost-utility of dapagliflozin for managing chronic kidney disease

Abstract

Background

Chronic kidney disease (CKD) is a significant public health concern. Dapagliflozin has been demonstrated to improve the quality of life for patients with CKD. This systematic review aimed to summarize the available evidence regarding the costs and cost-utility of dapagliflozin in managing CKD.

Methods

A systematic literature search was conducted from inception to October 24, 2025, using MEDLINE, EMBASE, and Scopus. Titles and abstracts were screened, followed by an eligibility assessment of full texts. The quality of the studies was evaluated using the Quality of Health Economic Studies (QHES) and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklists. Cost-utility results were synthesized narratively.

Results

The search strategies identified a total of 305 records, of which 8 articles were ultimately included in the review based on specified inclusion and exclusion criteria. All cost-utility studies were conducted over time horizons ranging from a lifetime to twenty years, with most outcomes derived from a single clinical trial. The highest incremental cost-utility ratio for dapagliflozin ($72,057.91/Quality-Adjusted Life Year) was reported in the USA. According to the available studies, adding dapagliflozin to standard care for CKD management is considered cost-effective from both the healthcare system and payer perspectives.

Conclusions

Incorporating dapagliflozin into standard care for managing CKD is generally regarded as cost-effective from both the healthcare system and payer perspectives. While dapagliflozin shows promise economically, further population-based studies are needed to confirm these findings.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s12962-026-00793-2.

Introduction

Chronic kidney disease (CKD) is a progressive and increasingly prevalent condition affecting more than 10% of the global population, representing a major public health challenge [1]. It is linked to high morbidity and mortality, considerable healthcare costs, and a substantial decline in quality of life. Beyond its impact on individuals, CKD places a significant strain on healthcare systems worldwide [1]. The global median prevalence of CKD stands at 9.5% [2] The burden of CKD is disproportionately higher among older adults, women, racial and ethnic minorities, and individuals with diabetes mellitus or hypertension [1].

Epidemiological trends are also concerning, with global mortality attributed to CKD increasing by 41.5% between 1990 and 2017 [1]. The economic impact is substantial; in high-income countries, approximately 2–3% of annual healthcare expenditures are allocated to the management of end-stage kidney disease [3]. Given this growing burden, effective management of CKD is essential. Current strategies emphasize reducing disease progression and complications through targeted control of blood pressure, lipid levels, glycemic status, and body weight. Addressing these key factors can improve patient outcomes and help mitigate the broader healthcare burden associated with CKD [4].

Sodium–glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of antidiabetic agents that reduce renal glucose reabsorption, thereby increasing urinary glucose excretion and lowering blood glucose levels. By binding to specific receptors, these powerful drugs promote the excretion of excess glucose in urine, leading to significant reductions in blood sugar levels [5]. Among these agents, dapagliflozin has gained particular attention and received U.S. FDA approval on April 30, 2021, for use in patients with CKD [6, 7].

Clinical evidence demonstrates that dapagliflozin reduces the risk of kidney function decline and progression to kidney failure, while also lowering rates of cardiovascular death and hospitalization for heart failure in adults with CKD [7]. Findings from key clinical trials further indicate that dapagliflozin slows disease progression, improves both renal and cardiovascular outcomes, reduces all-cause mortality, and maintains a favorable safety profile in patients with CKD, irrespective of diabetes status [8]. Collectively, this evidence highlights dapagliflozin as an important therapeutic option in the management of CKD, with the potential to improve patient outcomes and quality of life.

Economic considerations are as important as treatment efficacy and safety in evaluating therapeutic options. Cost-utility studies are generally favored over cost-effectiveness studies because they offer a more comprehensive assessment of health outcomes by integrating both the quantity and quality of life into a single metric, most commonly quality-adjusted life years [9]. This approach enables decision-makers to compare the value of diverse health interventions across various diseases and treatments using a standardized unit, which is not feasible with traditional cost-effectiveness analyses that depend on disease-specific outcomes. Furthermore, by incorporating patient preferences for different health states, cost-utility analysis provides a more patient-centered perspective, making it especially valuable for resource allocation decisions in healthcare systems that prioritize maximizing overall health benefit [9]. Several studies have assessed the cost-utility of dapagliflozin in the management of CKD. This systematic review aimed to synthesize the available evidence on the costs and cost-utility of dapagliflozin in patients with CKD.

Methods

Literature search strategy

This systematic review is reported in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [10]. The literature search utilized controlled vocabulary and relevant keyword terms. Preliminary searches were carried out in MEDLINE. The search strategy was also adapted for use in EMBASE, and Scopus (see Supplementary Appendix 1). The searches were conducted on October 24, 2025, covering all records published in English from the inception of these databases until that date. Additionally, the reference lists of the included studies were hand-searched, but this yielded no new records.

Selection of studies

This review focused on studies that conform to PICOS (population, intervention, comparison, outcomes, study design) criteria [9, 11]. The inclusion criteria of studies were as follows: (1) population: patients with CKD, (2) interventions: dapagliflozin, (3) comparators: no comparators were applied, (4) outcomes: incremental cost-utility ratio (ICUR), and (5) study design: cost-utility studies. The exclusion criteria consisted of letters to editors, review articles, conference abstracts, health technology assessment reports not submitted to peer review, protocols, and academic thesis.

This review focused on the ICUR as the main outcome of interest. Two independent reviewers, CS and RW-L, evaluated the titles, abstracts, and full texts of all relevant articles. They carefully screened the titles and abstracts to ensure alignment with the research objectives using Covidence. Only those articles that met all inclusion criteria proceeded to a detailed full-text review. The reviewers independently assessed the full texts of the eligible articles. Any disagreements that arose were resolved through constructive dialogue; if consensus could not be reached, a third reviewer was consulted to provide a final decision.

Data extraction

The data were extracted from the papers included by two independent reviewers (C.S. and R.W-L.). The following information was summarized from the literature: author, year, country; year of costing; patients; intervention and comparator; type of analysis; perspective; time horizon; willingness-to-pay threshold; discount rate; and sensitivity analyses. To ensure high consistency, both reviewers initially extracted data from four randomly selected publications. They then met to discuss any discrepancies in the extracted results, modified the extraction form as needed, and completed the data extraction from the remaining included studies. The extracted data were imported into Microsoft Excel.

Assessment of methodological quality

The Quality of Health Economic Studies (QHES) checklist [12] was utilized to rigorously evaluate the methodological quality of the included studies. This checklist stands out as a reliable and validated instrument, designed for ease of use while providing a clear quantitative assessment of a study’s quality [13]. Comprising 16 criteria, it requires straightforward “yes” or “no” responses, with each criterion allocated a weighted score ranging from 1 to 9 [12]. The resulting overall quality score can range from 0 to 100, with 0 indicating the lowest quality and 100 representing the highest of quality [12].

Assessment of reporting quality

The quality of reporting in the studies we included was rigorously evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist [14]. This comprehensive checklist consists of 28 essential items grouped into key categories: (1) title, (2) abstract, (3) introduction, (4) methods, (5) results, (6) discussion, and (7) additional pertinent information [14]. Each of 28 items was assessed for every study. We assigned a rating of “yes” if the item was reported, “no” if it was absent, or “na” if it was not applicable.

Data analysis

After assessing the literature quality and completing data extraction, the data were analyzed. The costs and ICUR were adjusted to 2025 USD ($) [15].

Results

Literature search and screening

Figure 1 presents a PRISMA flow diagram that outlines the study selection process. Initially, we identified a total of 305 studies, but after removing duplicates, 75 unique studies remained for consideration. Through a meticulous review of titles and abstracts, we excluded 62 studies that did not meet our criteria. Ultimately, we included 8 studies in our systematic review [16–23], reflecting a diverse range of research (Table 1).

Fig. 1.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart for study selection

Table 1.

Study characteristics

Author, year, Country	Year of Costing	Patients	Intervention and Comparator	Type of Analysis	Perspective	Time Horizon	WTP threshold (US$2025)	Discount rate, per year	Sensitivity analyses
Tisdale et al/, 2022; USA [16]	2019	Non-diabetic CKD	Dapagliflozin plus SoC versus SoC alone	CUA	Healthcare system	Lifetime	$ 120096.51/QALY	3%	Scenario Analyses, OWSA, and PSA
Vareesangthip et al., 2022; Thailand [17]	2020	CKD	Dapagliflozin in addition to SoC compared with SoC alone	CUA	Societal	Lifetime	$ 6127.76/QALY	3%	Scenario Analyses, OWSA, and PSA
Kodera et al., 2022; Japan [18]	Not reported	CKD stages 3a and 3b that was not limited to diabetic nephropathy	With and without dapagliflozin	CUA	Healthcare system	20 years	$56905.10/QALY	2%	Scenario Analyses, OWSA, and PSA
McEwan et al., 2022; UK, Germany, Spain [19]	2021	CKD	Dapagliflozin plus standard therapy vs. standard therapy	CUA	Payer	Lifetime	$31210.93/QALY (UK); $40279.24/QALY (Germany and Spain)	3.5% (UK), 3.0% (Germany), 3% (Spain)	Scenario Analyses, OWSA, and PSA
Swidan et al., 2023; Kuwait [20]	2022	CKD with or without type 2 diabetes	Dapagliflozin plus SoC versus ramipril	CUA	Societal	Lifetime	1–3 gross domestic product per capita	3.5	DSA and PSA
Nguyen et al.,2023; Canada [21]	2021	CKD and type 2 diabetes	Dapagliflozin plus SoC vs. SoC alone	CUA	Healthcare system	Lifetime	$47080.54/QALY	1.5%	Scenario analyses and OWSA
McEwan et al., 2024; UK, Spain, Italy and Japan [22]	2022	CKD with or without type 2 diabetes	Dapagliflozin plus SoC versus SoC alone	CUA	Healthcare system	Lifetime	$30510.98/QALY (UK), $41416.78/QALY (Spain), $37385.68/QALY (Italy), and $56905.00/QALY (Japan)	3.5% (UK), 3% (Spain), 3% (Italy), 2% (Japan)	Scenario Analyses, OWSA, and PSA
Lim et al., 2024; Malaysia [23]	2022	CKD with or without type 2 diabetes	Dapagliflozin as an add-on to SoC vs. SoC alone	CUA	Healthcare system	Lifetime	$11780.50/QALY	3%	OWSA and PSA

Abbreviations: CKD, chronic kidney disease; CUA, cost-utility analysis; DSA, deterministic sensitivity analysis; OWSA, one way sensitivity analysis; PSA, probabilistic

sensitivity analysis; QALY, quality adjusted life year; SoC, standard of care; WTP, willingness to pay

Study characteristics

In this review, eight articles assessing the economic implications of management of CKD in the USA [16], Thailand [17], Japan [18], Kuwait [20], Canada [21], and Malaysia [23], one study encompassed data from four countries (the UK, Spain, Italy, and Japan) [19], and one study covered three countries (the UK, Germany, and Spain) [22]. Notably, among these eight articles, four robust studies convincingly demonstrated that integrating dapagliflozin into the standard of care (SoC) not only enhances its effectiveness but also significantly reduces costs in Thailand [17], Kuwait [20], Canada [21], and Malaysia [23]. The remaining four studies revealed an ICUR ranging from $1365.73 to $72057.91 per quality-adjusted life year (QALY), both of which remain well within the acceptable willingness-to-pay (WTP) thresholds [16, 18, 19, 22]. Collectively, these findings underscore the compelling argument that dapagliflozin constitutes a highly cost-effective option for patients with CKD in these countries, potentially transforming patient care and management strategies (Table 1).

Design of the studies

Markov model was used in all of the 8 studies. Markov models are mathematical models, which can be used to simulate the disease progression and evaluate the cost-utility for two or more different management strategies [24]. All 8 studies also used the QALY as the measure of effectiveness [16–23].

Study perspective and willingness-to-pay thresholds

Among the studies analyzed, five were carried out from the health care system’s perspective [16, 18, 21–23], one from the payer’s perspective [19], and two from the societal perspective [17, 20]. This diverse range of viewpoints underscores the comprehensive nature of our research and highlights the multifaceted implications of the findings. From the healthcare system’s perspective, it is essential to focus exclusively on direct medical costs. However, when viewed from the third-party payer’s perspective, it becomes crucial to incorporate all direct medical costs covered by the insurance plan. Finally, from a societal perspective, a comprehensive evaluation must include not only all direct medical and non-medical costs but also consider the significant impact of indirect costs. Most of the studies were conducted using simulations based on a lifetime horizon [16, 17, 19–23], while one study specifically focused on a 20-year horizon [18]. This comprehensive approach underscores the long-term implications of the findings, highlighting their relevance and impact over extended periods.

The willingness-to-pay (WTP) thresholds from two studies in the UK were $31210.93/QALY, and $30510.98/QALY [19, 22]. In Spain, two studies reported WTP thresholds of $40279.24/QALY and $41416.78/QALY [19, 22]. Meanwhile, two studies in Japan identified WTP thresholds of $56905.10/QALY and $56905.00/QALY [18, 22]. Additionally, the WTP thresholds in Malaysia, Canada, Germany, the USA, Thailand, Italy and Kuwait were $33705.44/QALY, $47080.54/QALY, $40279.24/QALY, $120096.51/QALY, $6127.76/QALY, $37385.68/QALY, and 1–3 GDP per capita, respectively [16, 17, 19–23]. Furthermore, the discount rates ranged from 1.5% to 3.5% [16–23].

Main findings

All the studies were largely based on clinical trial data from DAPA-CKD [16–23]. One analysis utilized data from both DAPA-CKD and CKD-JAC [18]. Additionally, one study focused on the trials of DAPA-CKD and DECLARE-TIMI 58 [22]. A study was conducted on patients in the US who have non-diabetic CKD [16]. The results regarding costs are presented in Table 2. Out of the eight studies, four concluded that adding dapagliflozin to standard management can reduce the mean total cost [17, 20, 21, 23]. The outcomes related to QALY from all eight studies can also be found in Table 2.

Table 2.

Intervention costs, comparator costs, and QALYs

Author, year; Country	Intervention cost (Dapagliflozin) vs. Comparator cost (Standard of Care), US$ 2024	Intervention QALYs (Dapagliflozin) vs. Comparator QALYs (Standard of Care)
Tisdale et al/, 2022; USA [16]	$390193.56 vs. $295317.31	8.06 vs. 6.75
Vareesangthip et al., 2022; Thailand [17]	$20952.78 vs. $21887.92	5.10 vs. 4.80
Kodera et al., 2022; Japan [18]	3a: $114948.30 vs. $101291.08 3b: $145677.07 vs. $144538.97	3a: 16.9 vs. 16.6 3b: 16.2 vs. 15.6
McEwan et al., 2022; UK, Germany, Spain [19]	UK: $124340.01 vs. $116600.24 Germany: $288827.64 vs. $268779.35 Spain: $186117.46 vs. $173426.60	UK: 8.68 vs. 7.86 Germany: 10.32 vs. 9.32 Spain: 9.79 vs. 8.83
Swidan et al., 2023; Kuwait [20]	$206113.75 vs. $233415.34	3.5 vs. 3.3
Nguyen et al.,2023; Canada [21]	$204112.97 vs. $229313.29	8.24 vs. 6.81
McEwan et al., 2024; UK, Spain, Italy and Japan [22]	UK: $67053.77 vs. $61740.82 Spain: $165894.00 vs. $157616.59 Italy: $72096.34 vs. $67424.86 Japan: $93711.78 vs. $83882.15	UK: 9.56 vs. 9.09 Spin: 10.75 vs. 10.21 Italy: 11.16 vs. 10.60 Japan: 11.70 vs. 11.03
Lim et al., 2024; Malaysia [23]	$20952.78 vs. $21887.92	8.76 vs. 8.35

A study conducted in Malaysia revealed compelling results: the standard management generated 8.35 QALYs at a cost of $21887.92 [23]. However, when dapagliflozin was incorporated into the standard management, the QALYs rose to 8.76, and the cost decreased to $20952.78 [23]. This striking evidence suggests that adding dapagliflozin significantly enhances both the effectiveness and cost-efficiency of management in Malaysia, making it a compelling choice for improving patient outcomes [23].

A recent study conducted in Canada demonstrates that, from a healthcare system perspective over a lifetime horizon, dapagliflozin can yield an impressive 8.24 QALYs at a cost of $204112.97 [21]. In stark contrast, standard management alone achieves only 6.81 QALYs at a higher cost of $229313.29 [21]. The addition of dapagliflozin to standard management not only results in significant cost savings but also delivers superior health benefits measured in QALYs. Robust one-way sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) reinforce the validity of these findings. Therefore, incorporating dapagliflozin into standard management emerges as a more economically viable and effective approach for patients suffering from CKD and type 2 diabetes [21].

In two studies conducted in the UK, dapagliflozin demonstrated significant cost-utility, presenting an ICUR of just $9393.93 per QALY and $11319.29per QALY, respectively [19, 22]. A comprehensive evaluation by McEwan et al. in 2022 examined the cost-utility of dapagliflozin across the UK, Germany, and Spain, utilizing data from the DAPA-CKD trial [19]. The results were compelling: patients receiving dapagliflozin achieved QALYs of 8.68 in the UK, 10.32 in Germany, and 9.79 in Spain [19]. In contrast, those on standard management alone achieved lower QALYs, measuring 7.86, 9.32, and 8.83, respectively [19]. When evaluating costs, dapagliflozin proved to be a financially sound choice. The costs were $124340.01in the UK, $288827.64 in Germany, and $186117.46 in Spain for the dapagliflozin group [19]. In comparison, standard management incurred costs of $116600.24 in the UK, $268779.35 in Germany, and $173426.60 in Spain [19]. The ICURs for the respective countries were $9393.93 per QALY for the UK, $19993.83 per QALY for Germany, and $13259.25 per QALY for Spain [19].

In the study conducted by McEwan et al. in 2024, a comprehensive health-economic analysis revealed critical insights across the UK, Spain, Italy, and Japan [22]. The findings demonstrated that management with dapagliflozin led to significantly higher mean total costs compared to standard management in the UK, costs were $67053.77versus $61740.82; in Spain, $165894.00 compared to $157616.59; in Italy, $72096.34 versus $67424.86; and in Japan, $93711.78 compared to $83,882 [22]. However, these increased costs are accompanied by substantial benefits. Dapagliflozin proved to be markedly more effective in QALYs across all four nations. In the UK, patients achieved an impressive 9.56 QALYs compared to just 9.09 QALYs with standard management [22]. In Spain, the management resulted in 10.75 QALYs, surpassing the 10.21 QALYs of standard care [22]. Italian patients experienced 11.16 QALYs with dapagliflozin, a significant improvement over the 10.60 QALYs recorded for standard management [22]. In Japan, the drug delivered 11.70 QALYs, compared to 11.03 QALYs with standard care [22]. McEwan et al.‘s findings also indicated that dapagliflozin is considered cost-effective in Spain, Germany, and Italy [19, 22].

In addition to the study by McEwan et al. conducted in Japan in 2024, the research by Kodera et al. has provided compelling evidence regarding the cost-utility of dapagliflozin for managing CKD in Japan [18, 22]. For patients with CKD stage 3a, the total costs were $114948.30 and $101291.08 in the two groups, resulting in QALYs of 16.9 and 16.6, respectively [18]. For those with CKD stage 3b, the total costs were $145677.07 and $144538.97, with QALYs of 16.2 and 15.6 [18]. The ICUR was notably favorable, with $45865.52 per QALY for CKD stage 3a and an impressive $1365.73 per QALY for CKD stage 3b [18]. These results strongly indicate that dapagliflozin is not only an effective management strategy but also a highly cost-effective option for CKD management in Japan, highlighting its potential to significantly enhance patient outcomes while optimizing healthcare resources [18].

The other two studies were conducted in the United States and Thailand [16, 17]. In the US, the introduction of dapagliflozin resulted in an additional cost of $94876.25, delivering 1.31 QALYs. The ICUR was calculated at $72057.91 per QALY, highlighting the economic viability of this management. This study specifically assessed the impact of dapagliflozin on non-diabetic CKD in US patients [16]. Remarkably, subgroup analysis demonstrated that for individuals aged 70 and younger, the cost-utility was significantly more favorable for those with advanced stages of CKD. In particular, 40-year-old patients with stage 4 CKD experienced both enhanced effectiveness and lower costs with the addition of dapagliflozin [16]. In Thailand, the incorporation of dapagliflozin resulted in a striking cost reduction of $94876.25, coupled with an increase of 0.30 QALYs. Thus, it is evident that integrating dapagliflozin into standard management protocols is not only more effective but also more economical in Thailand [17]. In Kuwait, the combination of dapagliflozin and ramipril results in a significant improvement in QALY, with a notable difference of 0.2 when compared to ramipril alone [20]. Additionally, this combination approach leads to a cost savings of $27301.59.²⁰ In patients with CKD, dapagliflozin not only improved patient outcomes but also generated cost savings for those with CKD [20]. The findings from scenario analyses, OWSA, and PSA all affirm the robustness and reliability of these outcomes. Collectively, the evidence from these studies unequivocally supports that dapagliflozin is a highly cost-effective solution for CKD patients across all examined countries, making it a compelling choice for healthcare stakeholders.

Uncertainty in cost-utility results

The sensitivity analysis, encompassing scenario analyses, OWSA, and PSA, was performed across 8 articles examined [16–23]. The OWSA indicted several critical factors that significantly influenced the outcomes: time horizons [19, 22, 23] the decline in estimated glomerular filtration rate (eGFR) [21], the utility of chronic kidney disease (CKD), the costs associated with hemodialysis [18], the expenses of dapagliflozin [16], the likelihood of progression from CKD stage 3b to dialysis under SoC [17], and the overall survival distribution for dapagliflozin [20]. Overall, the OWSA analyses provided robust evidence supporting the reliability of the results, with notable exceptions highlighted in the studies by Tisdale et al. and Kodera et al. Tisdale et al. found that an increase in dapagliflozin pricing could shift its cost-utility into question [16]. Conversely, Kodera et al. findings emphasized that a decline in the utility value of CKD could similarly undermine the cost-utility of adding dapagliflozin.¹⁸ The PSA further illustrated that the probability of dapagliflozin being deemed cost-effective ranges impressively from 52.6% to 100% [16–19, 23]. Finally, the scenario analyses reinforced the conclusion that the results are generally resilient and robust.

Assessment of methodological quality

Table 3; Fig. 2 provide a summary of the methodological assessment of the QHES. All included studies clearly articulated their objectives in a measurable manner (Question 1). Each study utilized data from the Dapagliflozin and Prevention of Adverse Outcomes in CKD trial (Question 3). Furthermore, all studies reported their handling of uncertainty (Question 5), conducted incremental analyses to compare the costs and outcomes of the alternatives (Question 6), and described their data abstraction methodology (Question 7). They also defined the study’s time horizon and justified any discounting used (Question 8), clearly stated the measurements of cost (Question 9), and identified the primary outcome measures for the economic evaluation (Question 10). With the exception of one study [16], all ensured that health outcome measures and scales were valid and reliable (Question 11). Additionally, all studies employed decision-analytic models and adequately described their methods and analytical approaches (Question 12). The conclusions presented appeared reasonable based on the study results (Question 15), and all studies reported their sources of funding (Question 16). However, one study did not clearly state its perspective (Question 2) [18], two studies prespecified their subgroups (Question 4) [19, 22], none of the studies specified their choice of Markov model (Question 13), and none addressed the direction and magnitude of potential biases (Question 14).

Table 3.

Results of QHES assessment

Study	QHES question#
	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	Total
Tisdale et al. [16]	7	4	8	NA	9	6	5	7	8	6	0	8	3.5	0	8	3	82.5
Vareesangthip et al. [17]	7	4	8	NA	9	6	5	7	8	6	7	8	3.5	0	8	3	89.5
Kodera et al. [18]	7	0	8	NA	9	6	5	7	8	6	7	8	3.5	0	8	3	85.5
McEwan et al. [19]	7	4	8	1	9	6	5	7	8	6	7	8	3.5	0	8	3	90.5
Swidan et al. [20]	7	4	8	NA	9	6	5	7	8	6	7	8	3.5	0	8	3	89.5
Nguyen et al. [21]	7	4	8	NA	9	6	5	7	8	6	7	8	3.5	0	8	3	89.5
McEwan et al. [22]	7	4	8	1	9	6	5	7	8	6	7	8	3.5	0	8	3	90.5
Lim et al. [23]	7	4	8	0	9	6	5	7	8	6	7	8	3.5	0	8	3	89.5

NA, not applicable; QHES, Quality of Health Economic Studies

QHES checklist questions to examine methodological quality [12]:

Q1 - Was the study objective clearly defined?

Q2 - Were the study perspective and rationale for selecting the specific perspective stated?

Q3 - Were parameters used in the analysis based on the best available source of data?

Q4 - Was subgroup analysis prespecified at the beginning of the study?

Q5 - Was uncertainty assessed (statistical analysis for random events and sensitivity analysis for assumptions)?

Q6 - Was incremental analysis conducted between comparators?

Q7 - Was the methodology of data abstraction stated?

Q8 - Was an appropriate time horizon used? Were costs and outcomes discounted for a time horizon beyond one year?

Q9 - Was appropriate methodology used to estimate resource use and cost?

Q10 - Was the primary outcome measure of the study clearly stated?

Q11 - Were valid and reliable health outcome measurement scales used?

Q12 - Were the economic model, methods, and analysis described clearly and transparently?

Q13 - Were the choice of the modeling approach, assumptions, and limitations stated and justified?

Q14 - Were the direction and magnitude of potential biases discussed?

Q15 - Was there synergy between the study results and conclusions and recommendations?

Q16 - Was the source of funding disclosed?

Fig. 2.

Quality of health economic studies (QHES) checklist: summary of methodological quality of included studies

Assessment of reporting quality

The assessment of the reporting quality for the included studies, based on CHEERS criteria, is summarized in Table 4; Fig. 3. All studies clearly reported the following items: titles as economic evaluations (item #1), abstracts (item #2), background and objectives (item #3), study populations (item #5), settings and locations (item #6), comparators (item #7), perspective of analysis (item#8), time horizons (item #9), discount rates (item #10), selection of outcomes (item #11), measurement of outcomes (item #12), valuation of outcomes (item #13), measurement and valuation of resources and costs (item #14). Except for one study [18], all studies discussed currency, price dates, and conversions (item #15). They also provided detailed descriptions of the model (item #16), analytics and assumptions (item #17), uncertainty in the analysis (item #20), study parameters (item #22), summaries of main results (item #23), the impact of uncertainty (item #24), findings and limitations (item #26), sources of funding (item #27), and conflicts of interest (item #28).

Table 4.

Results of CHEERS 2022 assessment

Study	CHEERS item#
	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Tisdale et al. [16]	Y	Y	Y	N	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
Vareesangthip et al. [17]	Y	Y	Y	N	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
Kodera et al. [18]	Y	Y	Y	N	Y	Y	Y	N	Y	Y	Y	Y	Y	Y
McEwan et al. [19]	Y	Y	Y	\N	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
Swidan et al. [20]	Y	Y	Y	N	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
Nguyen et al. [21]	Y	Y	Y	N	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
McEwan et al. [22]	Y	Y	Y	N	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y
Lim et al. [23]	Y	Y	Y	N	Y	Y	Y	Y	Y	Y	Y	Y	Y	Y

Study	CHEERS item#
	15	16	17	18	19	20	21	22	23	24	25	26	27	28
Tisdale et al. [16]	Y	Y	Y	NA	N	Y	N	Y	Y	Y	N	Y	Y	Y
Vareesangthip et al. [17]	Y	Y	Y	NA	N	Y	N	Y	Y	Y	N	Y	Y	Y
Kodera et al. [18]	N	Y	Y	NA	N	Y	N	Y	Y	Y	N	Y	Y	Y
McEwan et al. [19]	Y	Y	Y	Y	N	Y	N	Y	Y	Y	N	Y	Y	Y
Swidan et al. [20]	Y	Y	Y	NA	N	Y	N	Y	Y	Y	N	Y	Y	Y
Nguyen et al. [21]	Y	Y	Y	NA	N	Y	N	Y	Y	Y	N	Y	Y	Y
McEwan et al. [22]	Y	Y	Y	Y	N	Y	N	Y	Y	Y	N	Y	Y	Y
Lim et al. [23]	Y	Y	Y	N	N	Y	N	Y	Y	Y	N	Y	Y	Y

CHEERS, Consolidated Health Economic Evaluation Reporting Standards; Y, yes; N, no; NA, not applicable

CHEERS criteria to examine quality of reporting [14]

1. The title indicates the study is an economic evaluation

2. Structured abstract summarizing context, methods, results, and alternative analyses

3. Background and objectives describe the context to conduct the study question and relevance for decision-making in policy or practice

4. A health economic analysis plan was developed and made available

5. Study population characteristics such as age, demographics, socioeconomic, or clinical characteristics are described

6. Contextual information that may influence study findings was reported

7. Comparators were described, and their choice was justified

8. Study perspective is stated, and its choice is justified

9. The time horizon of the study is stated and justified

10. Discount rate for costs and outcomes is stated and justified

11. Described outcomes used to measure benefit(s) and harm(s)

12. Described measurement of outcomes used to capture benefit(s) and harm(s)

13. The population and methods used to measure and value outcomes are described

14. Described measurement and valuation of resources used and costs

15. Reported currency used to measure costs, unit costs, and year of conversion

16. Described the model in detail and why it is used

17. Described methods used to transform data, extrapolating data, and model validation

18. Described methods used to estimate if results varied across subgroups

19. Described how impacts are distributed across different individuals or adjusted to reflect priority populations

20. Described methods used to characterize any sources of uncertainty in the analysis

21. Described approaches to engage patients or service recipients, the public, communities, or stakeholders (e.g., clinicians or payers) to design the study

22. Reported all analytic inputs (e.g., model input values, ranges, references), including uncertainty or distributional assumptions

23. Reported the mean values of costs and outcomes of interest and summarized them in an appropriate overall measure

24. Described whether uncertainty influenced model findings

25. Reported any difference in patient/service recipient, the public, community, or stakeholder involvement made to the approach or findings of the study

26. Reported key findings, limitations, ethical or equity considerations not captured, and how these could affect patients, policy, or practice

27. The source of funding and the role of the funder in the identification, design, conduct, and reporting of the analysis are reported

Fig. 3.

Consolidated health economic evaluation reporting standards (CHEERS) checklist: summary of reporting quality of included studies

Two [19, 22] out of the three studies [16, 19, 22] discussed subgroup analyses (item #18). None of the studies reported that a health economic analysis plan was developed and made available (item #4), characterized distributional effects (item #19), detailed approaches to engaging with patients and others affected by the study (item #21), or the effects of engagement with patients and others affected by the study (item #25).

Discussion

This systematic review critically evaluated eight original studies examining the cost-utility of dapagliflozin in patients with CKD. Overall, the evidence consistently indicates that dapagliflozin is a cost-effective and clinically valuable treatment option. Across all included studies, sensitivity analyses demonstrated stable and robust results, reinforcing the reliability of the findings. Both one-way sensitivity analyses (OWSA) and scenario analyses further supported the consistency of the economic outcomes. Notably, Tisdale et al. highlighted that the cost-utility of dapagliflozin is highly sensitive to drug pricing [16] In settings where prices are higher, affordability and access may be limited, whereas reductions in cost substantially improve cost-effectiveness, making the intervention more attractive for both patients and healthcare systems. In contrast, Kodera et al. reported that dapagliflozin may not be cost-effective for patients with CKD stage 3a in Japan, with a cost-effectiveness probability of only 52.6% [18]. This lower estimate likely reflects differences in event rates and patient characteristics across populations. In this subgroup, the annual incidence of dialysis initiation was extremely low (< 0.50%), meaning that relatively few patients progress to advanced renal replacement therapy, thereby limiting the economic benefits of treatment. These findings suggest that cost-utility in early-stage CKD may be more constrained in certain contexts, highlighting the need for further targeted research.

In contrast, most other studies reported a probability of cost-effectiveness exceeding 85%, supporting the overall robustness of the model results despite variability in input parameters. Subgroup analyses further suggested that dapagliflozin may be particularly cost-effective in patients without type 2 diabetes, those with a urine albumin–creatinine ratio (UACR) below 300 mg/g, and individuals with more advanced stages of CKD. These findings align with the observations of Kodera et al. and further support the targeted economic and clinical value of dapagliflozin in specific patient populations. Several studies also demonstrated that adding dapagliflozin to standard care improves outcomes while reducing overall healthcare costs. Evidence from Malaysia, Canada, and Thailand showed that patients receiving dapagliflozin in combination with standard management incurred lower total costs compared with standard care alone. This cost reduction is largely attributed to decreased rates of hospitalization for heart failure, acute kidney injury, and reduced need for renal replacement therapy, despite higher initial drug acquisition costs [17, 21, 23]. Overall, the findings support dapagliflozin as a cost-effective intervention in CKD management. The greatest economic benefits appear to be seen in patients without type 2 diabetes, those with higher UACR levels (≥ 300 mg/g), and individuals with more advanced CKD. These results suggest that appropriate patient selection may further enhance both clinical outcomes and long-term cost savings.

The methodological and reporting quality of the included studies was assessed using the QHES instrument and the CHEERS checklist. Most studies demonstrated high quality scores, indicating generally robust methodological approaches and adequate reporting standards. QHES evaluates several domains that may influence the validity of economic evaluations, including the transparency of assumptions, justification of data sources, handling of uncertainty, and appropriateness of analytic methods. Similarly, CHEERS promotes comprehensive reporting of model structure, assumptions, analytical methods, and characterization of uncertainty, thereby facilitating the critical appraisal of economic studies. Nevertheless, some variability in methodological quality and reporting practices was observed among the included studies. Differences in model structures, time horizons, costing approaches, assumptions, and healthcare settings may have contributed to the heterogeneity in cost-effectiveness estimates. Although the overall findings consistently supported the cost-utility of dapagliflozin, these methodological differences should be considered when interpreting the magnitude and transferability of the reported results across different healthcare systems and decision-making contexts. Furthermore, while QHES and CHEERS provide a comprehensive framework for assessing the methodological and reporting quality of economic evaluations, no single assessment instrument can fully capture every potential source of uncertainty inherent in model-based analyses. Therefore, the findings of this review should be interpreted in conjunction with the underlying assumptions and contextual factors of the individual studies.

Considerable heterogeneity was observed among the included studies with respect to healthcare setting, analytical perspective, time horizon, willingness-to-pay thresholds, discount rates, and costing approaches. Such variability is common in economic evaluations because model inputs and decision thresholds are often tailored to individual healthcare systems. Consequently, direct comparison of incremental cost-effectiveness ratios across studies should be undertaken cautiously. Additionally, several studies derived treatment-effect estimates from the DAPA-CKD trial, which served as the principal source of clinical evidence for dapagliflozin in patients with chronic kidney disease. Although reliance on a common evidence base may reduce the diversity of effectiveness inputs and partially limit external validity, the included studies differed substantially in their modeling approaches, assumptions, utility values, resource utilization estimates, and country-specific parameters. Therefore, the observed consistency in cost-effectiveness findings likely reflects both the robustness of the underlying clinical evidence and the adaptation of economic models to diverse healthcare settings. Nevertheless, future studies incorporating real-world evidence and alternative clinical data sources would further strengthen the generalizability of these findings.

This review focused exclusively on dapagliflozin and did not compare its cost-effectiveness with other SGLT2 inhibitors, such as empagliflozin or canagliflozin. Consequently, the findings should be interpreted within the context of dapagliflozin specific evidence, and future head-to-head economic evaluations i.e. dapagliflozin versus other SGLT2 inhibitors (e.g., empagliflozin or canagliflozin) are warranted to support healthcare decision-making across the SGLT2 inhibitor class. While this review provides important insights, several limitations should be acknowledged. First, this review was restricted to English-language publications and did not include grey literature sources, which may have resulted in language and publication bias. Because the review was limited to published studies, economic evaluations reporting unfavorable or non-significant results may be underrepresented. In addition, several included studies reported industry sponsorship or author affiliations with pharmaceutical manufacturers. Although methodological quality assessments indicated generally acceptable study quality, potential conflicts of interest may influence model assumptions, input selection, or interpretation of results. Therefore, the findings of this review should be interpreted alongside the reported funding sources and disclosures of the individual studies. Additionally, the review protocol was not prospectively registered, potentially limiting transparency and increasing the risk of selective reporting. Second, formal inter-rater agreement statistics were not calculated; however, disagreements between reviewers were resolved through discussion and, when necessary, consultation with a third reviewer to reach consensus. Third, cost-utility studies included in this review were predominantly conducted in high-income countries, with limited evidence from low- and middle-income settings and none from African countries. This limits the generalizability of the findings, as healthcare financing structures, drug pricing, reimbursement systems, and willingness-to-pay thresholds vary substantially across regions. Consequently, the cost-effectiveness results for dapagliflozin may not be directly transferable to resource-limited settings. There is a clear need for country-specific economic evaluations using local cost and epidemiological data to better inform decision-making in low-resource healthcare systems. Fourth, the majority of included studies were conducted in high-income countries, which limits the generalisability of the findings to low- and middle-income settings. The cost-utility of dapagliflozin in CKD therefore requires further evaluation in these regions to support more equitable and globally applicable healthcare decisions. Fifth, variation in time horizons across studies may introduce heterogeneity, reducing the comparability of results between countries and highlighting the need for more standardised methodological approaches. In addition, most analyses were conducted from either a healthcare system or payer perspective, with only two studies adopting a broader societal perspective. This may underestimate the full economic impact of CKD management strategies. Finally, the majority of cost-utility analyses were based on clinical trial data, which may not fully reflect real-world clinical practice and patient variability. To address these limitations, further long-term observational studies in real-world settings are needed to strengthen the evidence base and improve the external validity of findings. Such research would support more informed decision-making and ultimately contribute to improved patient outcomes globally.

Conclusions

This systematic review provides strong evidence on the cost-utility of adding dapagliflozin to standard care for CKD management. The available evidence suggests that dapagliflozin may be a cost-effective intervention for patients with chronic kidney disease in several healthcare settings. However, these findings should be interpreted in light of methodological heterogeneity, reliance on common clinical evidence sources, potential publication bias, and the influence of study funding and model assumptions. Further independent evaluations and real-world evidence are warranted to strengthen the evidence base. The evidence suggests that dapagliflozin is likely to be cost-effective in several high-income healthcare settings; however, to fully understand its broader economic impact, additional cost-utility studies are needed from a societal perspective and in low- and middle-income countries. Addressing these evidence gaps would improve the generalisability of findings and support more equitable access to treatment, potentially enhancing outcomes for CKD patients globally.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

Conceptualisation: RW-L, FX, CS; Screening, data extraction and quality assessment: RW-L, CS; Project administration: CS; Supervision: CS; Visualisation: CS; Writing-original draft: CS; Writing-review and editing: RW-L, FX, CS.

Funding

No funding was received for this study.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication (from patients/participants)

Not applicable.

Competing interests

The authors declare no competing interests.