Cost-utility analysis of glucagon-like peptide-1 receptor agonists for type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease in Thailand

Abstract

BACKGROUND

Metabolic dysfunction-associated steatotic liver disease (MASLD), a common chronic liver disease, is strongly associated with type 2 diabetes mellitus (T2DM). When accompanied by liver fibrosis, MASLD increases morbidity and mortality through metabolic risk and potential progression to cirrhosis and hepatocellular carcinoma. Glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated efficacy in reducing fibrosis severity in MASLD. However, their substantial cost limits widespread use in resource-limited settings.

AIM

To evaluate the cost-effectiveness of GLP-1 receptor agonists compared with usual care in Thai adults with T2DM and MASLD.

METHODS

A Markov model was used to estimate the lifetime health benefits and costs of GLP-1 receptor agonists in adults with T2DM and MASLD from a societal perspective. The model compared 3 treatment alternatives: Semaglutide, Liraglutide, and Usual care. Input parameters were derived from systematic reviews and local databases. The results were reported as incremental cost-effectiveness ratios (ICERs) in Thai baht (THB) per quality-adjusted life year (QALY) gained. Sensitivity and threshold analyses were performed.

RESULTS

The ICERs, compared with usual care, were 4580634 THB/QALY gained for semaglutide and 1709766 THB/QALY gained for liraglutide. At the willingness-to-pay threshold of 160000 THB/QALY gained, neither drug was cost-effective in Thailand. Price reductions of 96.51% for semaglutide and 90.64% for liraglutide would be required to achieve cost-effectiveness. One-way sensitivity analysis identified treatment efficacy, utility in MASLD stage F3, and the discount rate as the most influential parameters. Probabilistic sensitivity analysis confirmed these findings, with both treatments unlikely to be cost-effective relative to usual care.

CONCLUSION

Semaglutide and liraglutide are not cost-effective. Further clinical research and drug price negotiation are needed to make these treatments cost-effective and feasible in the Thai healthcare context.

Key Words: Cost-utility analysis; Diabetes mellitus; Glucagon-like peptide-1 receptor agonists; Metabolic dysfunction-associated steatotic liver disease; Thailand

Core Tip: This cost-utility analysis evaluated semaglutide and liraglutide for adults with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease in Thailand. Using a lifetime Markov model, we found that the incremental cost-effectiveness ratios of both drugs, relative to usual care, exceeded the national willingness-to-pay threshold. Neither drug was therefore cost-effective. Achieving cost-effectiveness would require price reductions exceeding 90%. These findings underscore the urgent need for drug price negotiations to improve treatment access within Thailand’s healthcare system.

INTRODUCTION

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease and is defined as steatosis on imaging or histology in the absence of excessive alcohol intake. MASLD affects an estimated one-third of the global population[1] and is still increasing[2]. Moreover, it affects 38% of the Thai population[3], and is associated with diabetes mellitus, obesity, and dyslipidemia. MASLD and metabolic syndrome appear to share a bidirectional relationship in which insulin resistance is the pathophysiological link[4,5]. Using National Health and Nutrition Examination Survey data, individuals with type 2 diabetes mellitus (T2DM) had an 11-fold increased risk of MASLD and those with prediabetes a 4-fold increased risk[6].

Hepatic fat accumulation can progress to metabolic dysfunction-associated steatohepatitis (MASH), which is present in 70% of the MASLD population in Asia[7]. Chronic hepatic inflammation triggers repair processes that lead to scarring, fibrosis, and eventually cirrhosis, which increases the risk of hepatocellular carcinoma. Although pharmacological treatments are approved for MASH with significant fibrosis, lifestyle modification remains the mainstay of treatment in Thailand due to limited drug accessibility and cost.

Glucagon-like peptide-1 (GLP-1) receptor agonists, used primarily to manage T2DM, stabilize blood glucose and are also indicated for weight reduction in people with overweight or obesity. Previous studies have shown that these agents reduce several scores used to assess liver fibrosis severity in people with diabetes. These include the aspartate aminotransferase-to-platelet ratio index, Fibrosis-4 index, non-alcoholic fatty liver disease (NAFLD) fibrosis score, and NAFLD activity score. In addition, GLP-1 receptor agonists facilitate recovery from MASH and liver fibrosis[8-16].

One of the earliest and best-known studies, the LEAN trial, provided initial evidence of the efficacy of liraglutide in MASH. Among participants who received liraglutide and underwent end-of-treatment liver biopsy, 39% achieved resolution of definite MASH, while 9% experienced fibrosis progression, compared with 9% and 36%, respectively, in the placebo group[9]. In a planned interim analysis of a subsequent trial, 63% of participants receiving semaglutide achieved MASH resolution without worsening of liver fibrosis, compared with 34% in the placebo group[17]. In addition, 37% of semaglutide recipients showed improvement in liver fibrosis without worsening of MASH, compared with 22% receiving placebo. This evidence led the United States Food and Drug Administration to approve semaglutide for MASH in adults with moderate-to-advanced fibrosis.

However, GLP-1 receptor agonists are high-cost medications. As Thailand is an upper middle-income country, economic evaluation of cost-effectiveness is a crucial tool for guiding budget allocation and the development of sound healthcare policies. Policies grounded in clinical evidence and economic evaluation would help ensure that patients receive optimal, cost-effective care, potentially reducing mortality, improving quality of life, and preventing unnecessary treatment complications. This, in turn, could lower overall national healthcare expenditure. To date, few studies in Thailand or internationally have examined the cost-effectiveness of GLP-1 receptor agonists for MASLD or MASH. The present study therefore performed a cost-utility analysis of GLP-1 receptor agonists, specifically semaglutide and liraglutide, for MASLD with significant fibrosis (stage ≥ F2) in Thailand.

MATERIALS AND METHODS

Overall description

A cost-utility analysis was performed to determine the lifetime health benefits, in quality-adjusted life years (QALYs), and costs of GLP-1 receptor agonist treatment in adults with T2DM and MASLD in Thailand. These costs included concomitant medications and direct nonmedical costs. A decision tree (Figure 1A) and a Markov model (Figure 1B) were used to examine overall costs and health outcomes over a patient’s lifetime from a societal perspective. The decision tree classified the target population into 3 treatment alternatives, and the Markov model simulated adults in each health state. The results were expressed as incremental cost-effectiveness ratios (ICERs) in 2023 Thai baht (THB) per QALY gained. A willingness-to-pay threshold of 160000 THB per QALY gained was applied to determine whether an alternative was cost-effective. All costs and outcomes were discounted at 3% per year. One-way and probabilistic sensitivity analyses were used to evaluate the influence of parameters, and a threshold analysis determined the drug prices at which treatment would be cost-effective. The analysis was conducted using Microsoft Excel 365.

Figure 1 Decision tree and Markov model. A: Decision tree; B: Markov model. In the decision tree, the square represents a decision node. The Markov model describes disease progression in metabolic dysfunction-associated steatotic liver disease. Arrows indicate possible patient transitions through the model. Solid arrows represent transition probabilities, whereas dashed arrows represent transitions to death states: Orange arrows indicate deaths from cardiovascular diseases, and black arrows indicate liver-related and other deaths. CVD: Cardiovascular disease; F: Fibrosis stage; HCC: Hepatocellular carcinoma; LR: Liver-related; MASLD: Metabolic dysfunction-associated steatotic liver disease; T2DM: Type 2 diabetes mellitus; Tp: Transition probability.

This article was prepared in accordance with the Consolidated Health Economic Evaluation Reporting Standards statement (Supplementary Table 1). The study protocol was approved by the Ethics Committee of the Faculty of Medicine Siriraj Hospital, Mahidol University (Si-568/2024).

Interventions and target population

We compared 3 therapeutic options: (1) Semaglutide; (2) Liraglutide; and (3) Usual care. Usual care consisted of routine outpatient visits every 3 months, together with lifestyle-modification counselling, laboratory monitoring, and medications for comorbid conditions such as diabetes mellitus, but excluded GLP-1 receptor agonists. Semaglutide and liraglutide were administered in addition to usual care. Liver biopsy with histological examination is the gold standard for diagnosing MASLD and liver fibrosis and for evaluating treatment response. We therefore restricted the analysis to semaglutide and liraglutide, the only GLP-1 receptor agonists supported by randomized controlled trials (RCTs) using this standard[18].

The standard dose of semaglutide was 2.4 mg once weekly. Liraglutide was given at 0.6 mg daily in week 1, 1.2 mg in week 2, and 1.8 mg from week 3 onward. The analysis evaluated GLP-1 receptor agonists in adults (aged ≥ 18 years) with T2DM and MASLD with significant fibrosis (stage ≥ F2), following the eligibility criteria of the pivotal clinical trials[9,17]. All hypothetical patients were assumed to start in MASLD fibrosis stage F2. Treatment efficacy was applied at this initial state and across subsequent progression to stages F3 and F4.

Economic model

After the target population was classified by the decision tree, a Markov model with a 1-year cycle length captured lifetime costs and health outcomes for each treatment option. The model comprised 11 health states representing the natural course of MASLD by fibrosis stage. These were MASLD stage F0 (no fibrosis), F1 (mild fibrosis), F2 (moderate fibrosis), F3 (severe fibrosis), F4 (compensated cirrhosis), decompensated cirrhosis, hepatocellular carcinoma, liver transplant, post-liver transplant, death from cardiovascular disease, and liver-related and other deaths. This model was adapted from a previous study[19].

At the beginning of the analysis, all hypothetical patients were assumed to have MASLD stage F2. We assumed that the disease could progress to the adjacent health state or to death. Patients who had not progressed beyond stage F4 could remain stable or regress to earlier fibrosis stages.

Input parameters

Input parameters were obtained from various sources and are summarized in Table 1. The efficacy of GLP-1 receptor agonists against liver fibrosis was derived from RCTs[9,17], whereas transition probability, mortality, and utility data were obtained from a literature review, systematic reviews, and meta-analyses[20-30]. Cost data were country-specific. Standard unit costs were drawn from the Drug and Medical Supply Information Center[31] and the Health Intervention and Technology Assessment Program of the Ministry of Public Health[32]. Primary data were obtained from the Siriraj Informatics and Data Innovation Center.

Table 1 Model input parameters.

Input parameters	Base-case	SE	Distribution	Source
Efficacy
Relative risk of improvement of at least 1 fibrosis stage without worsening of MASH
Semaglutide	1.334	0.160	Log-normal	[17]
Liraglutide	1.900	0.662	Log-normal	[9]
Transition probability
Fibrosis progression
MASLD F0 → MASLD F1	0.063	0.013	Beta	[20]
MASLD F1 → MASLD F2	0.067	0.013	Beta	[20]
MASLD F2 → MASLD F3	0.056	0.011	Beta	[20]
MASLD F3 → MASLD F4	0.044	0.009	Beta	[20]
MASLD F4 → HCC	0.008	0.002	Beta	[21]
MASLD F4 → DC	0.044	0.009	Beta	[21]
DC → HCC	0.029	0.006	Beta	[21]
DC → LT (Age ≤ 70)	0.003	0.001	Beta	[21]
DC → LT (Age > 70)	0	0	Beta	[21]
HCC → LT (Age ≤ 70)	0.012	0.002	Beta	[21]
HCC → LT (Age > 70)	0	0	Beta	[21]
Fibrosis regression
MASLD F1 → MASLD F0	0.025	0.005	Beta	[20]
MASLD F2 → MASLD F1
Semaglutide	0.060	0.012	Beta
Liraglutide	0.086	0.017	Beta
Usual care	0.045	0.009	Beta	[20]
MASLD F3 → MASLD F2
Semaglutide	0.078	0.016	Beta
Liraglutide	0.111	0.022	Beta
Usual care	0.058	0.012	Beta	[20]
MASLD F4 → MASLD F3
Semaglutide	0.061	0.012	Beta
Liraglutide	0.087	0.017	Beta
Usual care	0.046	0.009	Beta	[20]
Utility
MASLD F0 with T2DM	0.753	0.116	Beta	[22]
MASLD F1 with T2DM	0.753	0.116	Beta	[22]
MASLD F2 with T2DM	0.753	0.116	Beta	[22]
MASLD F3 with T2DM	0.753	0.116	Beta	[22]
MASLD F4/compensated cirrhosis with T2DM	0.748	0.042	Beta	[19]
Decompensated cirrhosis	0.603	0.022	Beta	[25]
HCC	0.310	0.062	Beta	[23,24]
Liver transplant	0.540	0.108	Beta	[23,24]
Post-liver transplant	0.683	0.015	Beta	[25]
Cost
Direct medical cost
Drug cost
Semaglutide			Gamma	[31]
Unit cost (THB/unit)	5585.00	1471.25
Monthly cost (THB/month)	7013.85	NA
Liraglutide			Gamma	[31]
Unit cost (THB/unit)	2337.95	584.49
Monthly cost (THB/month)	7062.00	NA
Direct medical and nonmedical costs (THB/year)
Treatment cost of usual care
MASLD F0 with T2DM	11753.85	4783.27	Gamma	Primary data[35]
MASLD F1 with T2DM	11753.85	4783.27	Gamma	Primary data[35]
MASLD F2 with T2DM	14742.15	6447.42	Gamma	Primary data[35]
MASLD F3 with T2DM	20830.97	7838.66	Gamma	Primary data[35]
MASLD F4/compensated cirrhosis	80469.83	20 117.46	Gamma	[19]
Decompensated cirrhosis	151209.14	37802.29	Gamma	[19]
HCC	184841.21	46210.30	Gamma	[19]
Liver transplant	683568.82	170892.20	Gamma	[19]
Post-liver transplant	110317.81	27579.45	Gamma	[19]

DC: Decompensated cirrhosis; F: Fibrosis stage; HCC: Hepatocellular carcinoma; LT: Liver transplant; MASH: Metabolic dysfunction-associated steatohepatitis; MASLD: Metabolic dysfunction-associated steatotic liver disease; NA: Not applicable; T2DM: Type 2 diabetes mellitus; THB: Thai baht.

Efficacy: The response to semaglutide and liraglutide, defined as improvement of at least 1 fibrosis stage without worsening of MASH in adults with T2DM, was derived from RCTs[9,17] (Table 2). From these outcomes, treatment efficacy relative to usual care was expressed as relative risks of 1.334 [95% confidence interval (CI): 0.976-1.824] for semaglutide and 1.900 (95%CI: 0.500-6.700) for liraglutide. These relative risks were applied to the transition probabilities from MASLD stage F2 to F1, F3 to F2, and F4 to F3.

Table 2 Studies of glucagon-like peptide-1 receptor agonists and improvement of ≥ 1 fibrosis stage without worsening of metabolic dysfunction-associated steatohepatitis in adults with diabetes mellitus.

Ref.	GLP-1 RA	n	Study design	Participants’ characteristics	Outcome
Sanyal et al[17]	Semaglutide	1197 (25.1%, Asia; 25.3%, Europe; 35%, North America; 7.9%, South America; 6.8%, other)	RCT	Demographics: Mean age: 56.3 years in semaglutide group, 55.4 in placebo group. Female: 58.6% in semaglutide group, 54.1% in placebo group. T2DM: 55.4% in semaglutide group, 56.8% in placebo group. Inclusion criteria: Age: 18 years or older. Liver biopsy with histological evidence of MASH and fibrosis stage 2 or 3. Exclusion criteria: (1) Excessive alcohol consumption1; (2) HbA1c > 9.5%; (3) AST or ALT > 5 × ULN at screening; (4) Chronic liver disease other than MASLD; (5) Hepatic decompensation or a MELD score > 12 at screening; and (6) Treatment with any GLP-1 RA or medication used for MASH at an unstable dose within 90 days before screening	Reduction in liver fibrosis without worsening of steatohepatitis: 34.5% in the semaglutide group and 25.6% in the placebo group
Armstrong et al[9]	Liraglutide	52 (88%, White; 4%, Asian; 2%, African or Caribbean; 6%, other)	RCT	Demographics: Mean age: 50 years in liraglutide group, 52 years in placebo group. Female: 31% in liraglutide group, 50% in placebo group. T2DM: 35% in liraglutide group, 31% in placebo group. Inclusion criteria: (1) Age: 18-70 years; (2) BMI ≥ 25 kg/m2 at screening; and (3) Liver biopsy with histological evidence of MASH obtained within 6 months of screening. Exclusion criteria: (1) Excessive alcohol consumption1; (2) Poor glycemic control (HbA1c > 9.0%); (3) Child-Pugh B or C cirrhosis; (4) Confounding concomitant drug use2; and (5) History of pancreatitis and pancreatic or thyroid carcinoma	Improvement of Kleiner fibrosis stage: 26% in the liraglutide group and 14% in the placebo group

¹Excessive alcohol consumption: > 20 g/day for women and > 30 g/day for men.

²Confounding concomitant drug use: Insulin, incretin mimetics, thiazolidinediones, vitamin E.

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; GLP-1 RA: Glucagon-like peptide-1 receptor agonist; HbA1c: Hemoglobin A1c; MASH: Metabolic dysfunction-associated steatohepatitis; MASLD: Metabolic dysfunction-associated steatotic liver disease; MELD: Model for end-stage liver disease; RCT: Randomized controlled trial; T2DM: Type 2 diabetes mellitus; ULN: Upper limit of normal.

Transition probability and mortality data: The transition probabilities used in the Markov model were derived from systematic reviews and meta-analyses[20,21], with standard errors calculated as 20% of the base-case values. Mortality rates were derived by combining age-specific mortality rates for the Thai population with cause-specific hazard ratios for each MASLD fibrosis stage[27-30] (Supplementary Tables 2-5). Age-specific mortality rates were obtained from the World Health Organization Life Table[26]. Sex-specific population proportions for Thailand were derived from the Registration Administration Office[33] and used to calculate weighted average mortality rates, which were subsequently converted to transition probabilities using the exponential distribution formula.

Cost data: From the societal perspective, the cost-utility analysis considered both direct medical and direct nonmedical costs. Indirect costs were excluded, in line with the Health Technology Assessment guideline[34], the QALY disutility already captures the lost or impaired capacity for work and leisure attributable to morbidity. Drug costs were calculated from the standard unit costs of the Drug and Medical Supply Information Center[31]. Direct nonmedical costs were taken from Thailand’s Standard Cost Lists for Health Economic Evaluation[32], as recommended by the Thailand Health Technology Assessment guideline, and supplemented with published Thai MASLD treatment costs[35].

In Table 1, direct nonmedical costs (i.e., food and transportation) were included in the usual-care treatment costs for each fibrosis stage. Patient-level medical treatment costs were obtained from the electronic database of Siriraj Hospital. Some cost inputs were reported in foreign currencies and were therefore converted to THB using the appropriate foreign exchange rates before the analysis[36]. Subsequently, annual costs were adjusted to 2023 values using the Consumer Price Index[37]. Standard errors for medical and direct nonmedical costs at MASLD fibrosis stages F0-F3 were obtained from the primary data. Fibrosis stage in the primary data cohort was classified using transient elastography, a validated non-invasive method for assessing liver fibrosis. For MASLD stage F4, decompensated cirrhosis, hepatocellular carcinoma, liver transplant, post-liver transplant, and drug prices, standard errors were calculated as 25% of the base-case values.

Utility: Utility is a health-related quality-of-life measure ranging from 0 (death) to 1 (perfect health). The baseline utility of 0.753 was derived from adults with T2DM but without related complications and was applied to MASLD stages F0-F3[22]. To estimate the QALYs for each health state, lifetime was weighted by utility values from a literature review[23,24] (Table 3). Utility values for decompensated cirrhosis and liver transplantation were obtained from observational studies conducted in Thailand where patients older than 70 years were assumed to be ineligible for liver transplantation[25]. The corresponding standard errors were likewise based on the original values reported in the literature.

Table 3 Studies of health-state utilities in liver disease.

Ref.	n	Study design	Participants’ characteristics	Outcome
McLernon et al[24]	30 studies from the United States, Canada, the United Kingdom, Germany, Australia, Italy, and the Netherlands	Systematic review	Inclusion criteria: English-language studies of any design that had: (1) Measured utility using health-state utility tools from liver disease patients, physicians, or adults with no liver disease; or (2) Estimated health-state utilities for various liver diseases from expert opinion. Exclusion criteria: (1) Letters, comments, news articles; (2) Studies unrelated to liver disease; (3) Utility estimates taken from the literature; (4) Insufficient information on how the utility was derived; and (5) Duplicate utilities from the same population	The utility of compensated cirrhosis was 0.748
Levy et al[23]	600 people (100 each from the United States, Canada, the United Kingdom, Spain, Hong Kong, and China)	Descriptive (using an interviewer-administered survey)	Demographics: Mean age: 41.5 years, female: 57.3%. Inclusion criteria: Age 18 years or older; Exclusion criteria: Inability to communicate in the official language(s) of the country, known cognitive impairment, or visible intoxication	In China, the utilities of HCC, liver transplant, and post-liver transplant were 0.310, 0.540, and 0.683, respectively

HCC: Hepatocellular carcinoma.

Cost-utility analysis

Base-case analysis: The base-case model assumed continuous use of GLP-1 receptor agonists in adults with T2DM and MASLD stages F2-F4. Costs and outcomes were compared with usual care and reported as incremental costs, incremental QALYs, and ICERs in THB per QALY gained.

Sensitivity analyses: Sensitivity analyses assessed how the variability of each parameter influenced the model. One-way sensitivity analyses were performed by varying input parameters within the ranges specified above, and the results were presented as tornado diagrams. A threshold analysis was used to determine the cost-effective prices of the treatment options. In addition, multivariate probabilistic sensitivity analyses were conducted with 1000 Monte Carlo simulations to explore parameter uncertainty. Transition probabilities and utilities were assigned a beta distribution, cost data a gamma distribution, and relative risks a log-normal distribution. The probabilistic results were presented as a cost-effectiveness plane and cost-effectiveness acceptability curves, showing the probability that GLP-1 receptor agonists would be cost-effective compared with usual care.

RESULTS

Base-case analysis

Table 4 shows the total cost of each treatment in the base-case analysis. These were 494792.07 THB for usual care, 1876919.28 THB for semaglutide, and 1668179.51 THB for liraglutide. Compared with usual care, the incremental cost was 1382127.20 THB for semaglutide and 1173387.43 THB for liraglutide. Semaglutide yielded 18.12 QALYs and liraglutide 18.50 QALYs. Liraglutide therefore dominated semaglutide, providing more QALYs at a lower total lifetime cost. Usual care was chosen as the reference strategy because it reflects current practice. Relative to usual care, the ICER was 4580633.86 THB/QALY gained for semaglutide and 1709766.30 THB/QALY gained for liraglutide. At a willingness-to-pay threshold of 160000 THB/QALY gained, neither drug was cost-effective.

Table 4 Results of the base-case analysis.

Regimen	Cost (THB)	QALYs	Incremental cost (THB)	Incremental QALYs	ICER (THB/QALY gained)
Usual care	494792.07	17.82
Semaglutide	1876919.28	18.12	1382127.20	0.30	4580633.86
Liraglutide	1668179.51	18.50	1173387.43	0.68	1709766.30

ICER: Incremental cost-effectiveness ratio; QALY: Quality-adjusted life year; THB: Thai baht.

Sensitivity analysis

The one-way sensitivity analysis is shown as tornado diagrams in Figure 2. For semaglutide, the 5 most influential parameters were its efficacy, the utility of MASLD stage F3, the outcome discount rate, the utility of MASLD stage F1, and the cost of semaglutide. For liraglutide, they were its efficacy, the outcome discount rate, the utilities of MASLD stages F3 and F1, and the cost of liraglutide. Overall, drug efficacy, the outcome discount rate, the utilities of MASLD stages F1 and F3, and drug costs were the most influential parameters.

Figure 2 Tornado diagrams. A: Semaglutide compared with usual care; B: Liraglutide compared with usual care. The vertical axis lists the model parameters ordered by their magnitude of influence on the incremental cost-effectiveness ratio (ICER). The horizontal axis shows the ICER range as each parameter is varied between its minimum and maximum value. DC: Decompensated cirrhosis; DM: Diabetes mellitus; F: Fibrosis stage; ICER: Incremental cost-effectiveness ratio; MASLD: Metabolic dysfunction-associated steatotic liver disease; QALY: Quality-adjusted life year; THB: Thai baht; Tp: Transition probability.

The probabilistic sensitivity analyses for semaglutide and liraglutide are presented as a cost-effectiveness plane and cost-effectiveness acceptability curves in Figure 3. Both drugs were unlikely to be cost-effective, with a probability of cost-effectiveness near 0% at the current willingness-to-pay threshold. Across willingness-to-pay thresholds from 0 THB to 3000000 THB, neither treatment was cost-effective compared with usual care.

Figure 3 Probabilistic sensitivity analyses. A: Cost-effectiveness plane showing incremental cost (THB) on the vertical axis against quality-adjusted life year (QALY) gained on the horizontal axis; B: Cost-effectiveness acceptability curve for semaglutide compared with usual care; C: Cost-effectiveness acceptability curve for liraglutide compared with usual care. In the cost-effectiveness acceptability curves, the vertical axis represents the probability of being cost-effective, and the horizontal axis shows willingness-to-pay (WTP) values. The dashed gray line represents the WTP threshold (THB/QALY gained). QALY: Quality-adjusted life year; THB: Thai baht; WTP: Willingness-to-pay.

Threshold analyses were performed in the base-case scenario to determine the optimal drug prices. Price reductions of 96.51% for semaglutide and 90.64% for liraglutide would be required for these treatments to become cost-effective.

DISCUSSION

This study evaluated the cost-effectiveness of the GLP-1 receptor agonists semaglutide and liraglutide for MASLD with significant fibrosis (stage ≥ F2) in Thailand. At current prices, both drugs were not cost-effective in the Thai context, although liraglutide showed a more favorable cost-effectiveness profile than semaglutide. This difference was driven mainly by efficacy estimates from the RCTs, in which liraglutide had a higher relative risk of fibrosis improvement vs usual care than semaglutide. The greater efficacy of liraglutide meant fewer patients progressed to severe MASLD health states, which lowered total lifetime costs and increased QALYs. Meanwhile, the maintenance medication costs of the 2 drugs were comparable.

Previous studies have assessed the economic value of various pharmacological treatments for MASLD in Thailand, beyond weight-reduction programs. Pioglitazone, often evaluated for its ability to normalize glucose metabolism in MASLD, can cause mild adverse effects such as weight gain. One systematic review compared pioglitazone, vitamin E, and their combination with other MASLD and MASH interventions, drawing on RCTs, systematic reviews, and meta-analyses. It examined their effects on liver histology, liver markers, and lipid profile. The review found that pioglitazone and vitamin E reduced steatosis, inflammation, ballooning, and liver markers, although evidence on fibrosis resolution remained conflicting[38].

MASLD progression from simple steatosis through MASH and liver fibrosis to hepatocellular carcinoma reflects lipotoxicity from excess serum free fatty acids in hepatocytes. In insulin resistance, impaired insulin-mediated suppression of lipolysis releases excess free fatty acids into the bloodstream. Beyond this abnormal lipid metabolism, insulin resistance can also promote MASLD through inflammatory processes by upregulating genes that encode inflammatory cytokines[4]. We therefore focused on adults with T2DM and evaluated pharmacological treatments that improve insulin resistance to reduce liver fibrosis, a population not addressed by the previous review.

Insulin resistance plays a central role in the pathogenesis of MASLD and liver fibrosis. Recent research therefore provides a robust foundation for evaluating the cost-effectiveness of managing MASH in adults with T2DM within the Thai healthcare context. One such study[39], which included Thailand among 12 target countries spanning all 6 World Health Organization regions, offers important insights into the economic value of different diagnostic and therapeutic pathways. It found that standard of care, defined as no screening or treatment intervention, yielded the lowest average cost-effectiveness ratios in 8 countries, including Thailand. Intensive lifestyle intervention after screening was cost-effective in all countries, and the combination of intensive lifestyle intervention and semaglutide was cost-effective in Thailand, whereas other pharmacological treatments, such as resmetirom, were not[39].

Because country-specific data on key parameters were limited, that analysis may not fully capture the clinical context of each country. To our knowledge, ours is the first health economic evaluation of GLP-1 receptor agonists in adults with T2DM and MASLD with significant fibrosis in Thailand, using country-specific data to the greatest extent possible.

Limitations

Although our study compiled substantial supporting evidence, several limitations remain. Only a limited number of RCTs met the predefined inclusion criteria and reported outcomes suitable for parameterization in the economic model. Consequently, the efficacy estimates for both agents were derived from a relatively small evidence base, and only a few studies reported histologically confirmed MASLD and liver fibrosis based on liver biopsy. Furthermore, we assumed equal efficacy for fibrosis improvement across stages F2-F4, whereas the treatment effect may in reality differ by fibrosis severity. These factors may have introduced uncertainty into our base-case analysis. Nevertheless, the efficacy values for each drug were chosen to align as closely as possible with the study design and clinical context. Moreover, the sensitivity analyses suggested that both drugs are unlikely to be cost-effective under the current context.

This study drew on outpatient and inpatient data from the local hospital database, which also included visits for conditions other than MASLD. To address this and improve feasibility, we assumed that each patient attended quarterly outpatient visits for MASLD management when calculating treatment costs. Each hypothetical patient who regressed to MASLD stage F0 or F1 was assumed to receive usual care, and costs were calculated accordingly, even though such patients may have had no clinical manifestations. This assumption may have introduced inaccuracies into the MASLD cost estimates and skewed the cost-effectiveness analyses.

Other potential benefits of GLP-1 receptor agonists, including improvements in body weight, glycemic control, and cardiovascular risk, were not directly incorporated into the analysis as reliable data were limited. These effects may provide additional benefits beyond liver-related outcomes, such as improving overall patient outcomes and reducing mortality from nonhepatic causes. Consequently, our model may have slightly underestimated the overall cost-effectiveness of GLP-1 receptor agonists.

Strengths

A key strength of this study is the use of comprehensive cost data, drawing on both direct medical and direct nonmedical costs from established institutional records and Thai-specific local datasets. This approach yields contextually relevant, accurate cost estimates and strengthens the applicability and reliability of our findings within the Thai healthcare setting. Our model also stratified mortality into liver-related, cardiovascular-related, and other causes. This stratification sharpens the specificity of our estimates and aligns the mortality outcomes with the study focus, supporting a more accurate and nuanced analysis. Finally, we conducted a comprehensive cost-utility analysis that paired sensitivity analyses, to assess model robustness, with a threshold analysis. The threshold analysis identified the drug prices at which the interventions would be cost-effective in the Thai context.

CONCLUSION

Although current guidelines and clinical trials support GLP-1 receptor agonists for treating T2DM, with the added benefit of reducing liver fibrosis in MASLD, both semaglutide and liraglutide impose a substantial financial burden. At their current prices, they are not cost-effective in the Thai healthcare context. Our threshold analysis identified the price at which these treatments could become cost-effective and may inform further clinical research and drug price negotiations. These strategies could then be incorporated into clinical practice to improve MASLD management within Thailand’s healthcare system.

ACKNOWLEDGEMENTS

We express our gratitude to Euarat Mepramoon for her contributions to project coordination.