Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial

Table 1 Baseline characteristics of subjects

	Placebo (n = 6)	Sitagliptin (n = 6)
Demographics
Age (yr)	54.7 ± 9.8	56.7 ± 9.9
Gender - male, n (%)	2 (33)	3 (50)
White, n (%	6 (100	5 (83)
Weight (kg)	105.8 ± 23.5	100.4 ± 28.7
BMI (kg/m2)	37.4 ± 4.7	35.9 ± 6.6
Diabetes duration (yr)1	6.0 (5.0, 6.0)	6.5 (5.0, 23.0)
NASH Duration (yr)1	4.0 (1.0, 4.0)	1.3 (0.1, 2.0)
Biochemical profile
HbA1C (%)	8.2 ± 0.9	7.9 ± 1.0
HOMA-IR	3.5 ± 2.2	3.4 ± 1.2
Fasting glucose (mmol/L)	11.3 ± 4.9	8.1 ± 3.1
Fasting insulin (pmol/L)	165 ± 134	168 ± 63
AST (IU/L)	39 ± 19	44 ± 22
ALT (IU/L)	46 ± 36	72 ± 50
Alkaline phosphatase (IU/L)	85 ± 34	93 ± 41
GGT (IU/L)	100 ± 98	164 ± 182
Triglycerides (mmol/L)	2.33 ± 2.00	2.80 ± 1.64
HDL-C (mmol/L)	1.10 ± 0.34	1.12 ± 0.46
LDL-C (mmol/L)	1.61 ± 0.71	1.42 ± 0.97
Free fatty acids (μmol/L)	645 ± 195	559 ± 158
Platelet aggregation (PRU)	292 ± 37	236 ± 28
Histologic profile
Fibrosis	2.2 ± 0.8	2.2 ± 1.0
NAS	4.2 ± 1.5	3.8 ± 0.8
Steatosis	1.8 ± 0.8	1.8 ± 0.8
Lobular Inflammation	1.2 ± 0.4	1.0 ± 0
Ballooning	1.2 ± 0.4	1.0 ± 0
MRI
Hepatic fat (%)	21.9 ± 10.6	19.0 ± 9.7
SAAT (%)	40.5 ± 7.1	38.0 ± 22.0
VAT (%)	30.5 ± 3.4	26.8 ± 11.6
Left thigh fat (%)	37.8 ± 9.9	39.5 ± 15.8

¹Data are presented as median (Q1, Q3). Data are presented as mean ± SD, unless otherwise specified. ALT: Alanine aminotransferase; AST: Aspartate transferase; BMI: Body mass index; HbA1C: Hemoglobin A1C; HOMA-IR: Homeostasis model of assessment for insulin resistance; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; NAS: Non-alcoholic fatty liver disease activity score; NASH: Non-alcoholic steatohepatitis; MRI: Magnetic resonance imaging; PRU: Platelet reaction units; SAAT: Subcutaneous abdominal adipose tissue; VAT: Visceral adipose tissue.

Table 2 Changes in primary and secondary histologic outcomes after 6 mo of treatment with sitagliptin vs placebo

	Placebo (n = 6)			Sitagliptin (n = 6)			Difference
	Baseline	Post-treatment1	P value	Baseline	Post-treatment1	P value	(95%CI)	P value
Primary outcome
Fibrosis	2.2 ± 0.8	2.0 ± 1.0	0.85	2.2 ± 1.0	2.4 ± 1.1	0.85	0.4 (-0.98, 1.78)	0.82
Secondary outcomes
NAS	4.2 ± 1.5	3.8 ± 1.9	0.50	3.8 ± 0.8	3.4 ± 1.5	0.85	0.2 (-1.62, 2.02)	1.00
Steatosis	1.8 ± 0.8	1.6 ± 0.9	0.62	1.8 ± 0.8	1.4 ± 0.9	0.55	0 (-1.08, 1.08)	0.91
Hepatocyte ballooning	1.2 ± 0.4	1.4 ± 0.9	0.89	1.0 ± 0	0.8 ± 0.4	0.36	-0.40 (-1.05, 0.25)	0.23
Lobular inflammation	1.2 ± 0.4	0.8 ± 0.4	0.22	1.0 ± 0	1.2 ± 0.4	0.36	0.60 (-0.13, 1.33)	0.12

¹Data only available for 5 subjects. Data are presented as mean ± SD. NAS: Non-alcoholic fatty liver disease activity score.

Table 3 Changes in anthropometric, biochemical, and MRI parameters after 6 mo of treatment with sitagliptin vs placebo

	Placebo (n = 6)		Sitagliptin (n = 6)		Difference
	Baseline	Post-treatment	Baseline	Post-treatment1	(95%CI)
Anthropometric and biochemical parameters
Weight (kg)	105.8 ± 23.5	104.7 ± 23.7	100.4 ± 28.7	101.1 ± 32.4	0.8 (-6.3, 8.0)
BMI (kg/m2)	37.4 ± 4.7	36.8 ± 4.6	35.9 ± 6.6	35.8 ± 8.0	0.6 (-2.8, 4.0)
HbA1C (%)	8.2 ± 0.9	8.0 ± 1.7	7.9 ± 1.0	6.7 ± 0.4a	-0.7 (-1.7, 0.4)
HOMA-IR	3.5 ± 2.2	2.73 ± 1.631	3.4 ± 1.2	3.5 ± 2.9	-0.36 (-3.3,2.6)
Triglycerides (mmol/L)	2.33 ± 2.00	2.29 ± 1.40	2.80 ± 1.64	1.26 ± 0.43b	-1.10 (-2.88, 0.66)
HDL-C (mmol/L)	1.10 ± 0.34	1.11 ± 0.29	1.12 ± 0.46	1.12 ± 0.40	-0.05 (-0.32, 0.22)
LDL-C (mmol/L)	1.61 ± 0.71	1.42 ± 0.34	1.42 ± 0.97	1.54 ± 0.51	0.30 (-0.17, 0.77)
Free fatty acids (μmol/L)	645 ± 195	914 ± 411	559 ± 158	488 ± 270	-143 (-788, 503)
Platelet aggregation (PRU)	292 ± 37	266 ± 63	236 ± 28	251 ± 74	-11 (-92, 70)
AST (IU/L)	39 ± 19	42 ± 23	44 ± 22	35 ± 9	-5 (-36, 26)
ALT (IU/L)	46 ± 36	48 ± 28	72 ± 50	51 ± 15	-5 (-51, 41)
Alk phos (IU/L)	85 ± 34	97 ± 43	93 ± 41	76 ± 28	-14 (-36, 7)
GGT (IU/L)	100 ± 98	153 ± 176	164 ± 182	90 ± 76	-62 (-164, 39)
Adiponectin (μg/mL)	2.01 ± 1.30	2.09 ± 1.14	3.93 ± 2.65	4.70 ± 3.46b	0.60 (-0.13, 1.32)c
Adipsin (μg/mL)	0.62 ± 0.26	0.61 ± 0.26	0.66 ± 0.14	0.62 ± 0.07	-0.07 (-0.26, 0.13)
Visfatin (ng/mL)	3.21 ± 3.64	3.94 ± 3.59	1.82 ± 2.33	1.70 ± 1.08	-0.58 (-3.26, 2.09)
Leptin (ng/mL)	14.62 ± 12.52	17.64 ± 16.20	9.61 ± 3.29	8.87 ± 5.54	-3.5 (-8.6, 1.6)
Resistin (ng/mL)	3.66 ± 1.01	4.31 ± 1.66	7.19 ± 8.66	4.55 ± 1.73	-4.05 (-11.33, 2.34)
TNF-α (pg/mL)	3.69 ± 1.22	4.95 ± 4.79	2.85 ± 0.66	5.14 ± 3.20	0.95 (-4.70, 6.61)
IL-6 (pg/mL)	5.89 ± 1.37	6.19 ± 2.37	7.15 ± 6.22	6.40 ± 3.41	-1.44 (-7.76, 4.87)
MRI parameters
Hepatic fat (%)	21.9 ± 10.6	19.1 ± 9.6	19.0 ± 9.7	16.1 ± 12.9	2.0 (-7.3, 11.2)
SAAT (%)	40.5 ± 7.1	39.8 ± 7.7	38.0 ± 22.0	34.1 ± 20.1	0.7 (-2.3, 3.7)
VAT (%)	30.5 ± 3.4	30.3 ± 4.4	26.8 ± 11.6	27.6 ± 13.4	0 (-6.4, 6.4)

¹One subject was excluded from the post-treatment, placebo group homeostasis model of assessment for insulin resistance (HOMA-IR) calculation due to blood glucose level above the acceptable steady-state glucose value for calculation of HOMA-IR.

^aP < 0.05 vs baseline;

^bP < 0.10 vs baseline;

^cP < 0.10 vs control.