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

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.

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.

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.

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.