Table 2 Studies of GLP-1 agonists to treat nonalcoholic fatty liver disease

Armstrong, 2013 [21] Multinational LEAD & LEAD-2 (fair)

Patients with type 2 diabetes who were unable to maintain glycemic control (HbA1c ≥ 7%) with diet and exercise alone, or with oral antidiabetic treatment

Age: 55.9 years

Gender, %

Female: 46.5

Ethnicity, %:

White: 78.6

Asian/Hawaiian/Pacific Islander: 12.7

Black/African American: 5.8

Other: 2.1

BMI: NR

NAFLD/NASH Stage: NR

Liver enzymes (IU/L):

Total ALT mean (SD): 29.4 (16.6)

Normal ALT mean (SD): 19.1 (5.6)

Abnormal ALT mean (SD): 39.4 (17.7)

LEAD

A: Liraglutide 0.6 mg/day (475)

B: Liraglutide 1.2 mg/day (896)

C: Liraglutide 1.8 mg/day (1363)

D: Placebo (524)

Duration: 26 weeks

LEAD-2

0.6, 1.2, or 1.8 mg/day liraglutide, 4 mg/day glimepiride or placebo, all in combination

with metformin

LEAD

In patients with elevated ALT, liraglutide 1.8 significantly reduced ALT compared with placebo (and was dose responsive); however, after correcting for change in weight, the difference was no longer significant: Mean difference − 1.41, P = 0.21, with similar finding after correcting for reduction in HbA1c: Mean difference 0.57, P = 0.63. Lower doses of liraglutide had similar effects as placebo

LEAD2

64% of patients had elevated liver fat on CT; as above liraglutide improved liver fat in a dose dependent way; however, there was no significant differences between liraglutide and placebo after correcting either for weight loss or HbA1c (P = 0.90 and 0.73, respectively)

LEAD

WAE: 9% vs. 9% vs. 3% (liraglutide vs. placebo, P < 0.001)

SAE: 7% vs. 6% vs. 6%

GI disorders: 46% vs. 45% vs. 18% (liraglutide vs. placebo, P < 0.001)

LEAD2

NR

Armstrong, 2016 [9]

UK

LEAN (good)

Patients had histologically confirmed NASH

Age: 51

Sex: 60% male

Ethnicity:

White: 88%

Asian: 4%

Black: 2%

Other: 6%

Liver status: NAS: 4.9;

ALT: 72 IU/mL; F3-F4: 52%

BMI: 36

Diabetes: 33%

A. Liraglutide 1.8 mg (26)

B. Placebo (26)

Duration: 48 weeks

Resolution of NASH: 39% vs. 9% (RR 4.3, 95% CI 1.0 to 17.7)

Change in NAS: − 1.3 vs. − 0.8, P = 0.24

Change in fibrosis stage: − 0.2 vs. 0.2, P = 0.11

Patients with improvement in fibrosis: 26% vs. 14%, P = 0.46

Patient with worsening fibrosis: 9% vs. 36%, P = 0.04

Change in ALT: − 26.6 vs. − 10.2, P = 0.16

Change in AST: − 27 vs. + 9 IU/L; P = 0.025

WAE: 8% vs. 4% (P = 0.56)

SAE: 8% vs. 8%

GI disorders: 81% vs. 65% (P = 0.27)

Shao, 2014 [8] China (fair)

Patients with type 2 diabetes, obesity, NAFLD, and elevated liver enzymes with normal renal function

Age: 43

Sex: 48% male

Ethnicity: Chinese

Mild NAFLD: 40%

Moderate NAFLD: 42%

Severe: 18%

BMI: 30

HbA1c: 7.64%

A. exenatide + glargine (30)

B. Intensive insulin: Insulin aspart + insulin glargine (30)

Duration: 12 weeks

Reversal rate of NAFLD based on ultrasound:

A vs. B: 93% vs. 67% , P < 0.01

Differences in weight change post minus pretreatment:

A vs. B: − 7.77 kg vs. 3.27, P < 0.001

No difference between groups in change in HbA1c:

A vs. B: − 1.42% vs. − 1.31%, P > 0.05

NR