Effects of ALT-801, a GLP-1 and glucagon receptor dual agonist, in a translational mouse model of non-alcoholic steatohepatitis.

Nestor JJ, Parkes D, Feigh M, Suschak JJ, Harris MS

Scientific reports23 Apr 2022Cited by 43 (Europe PMC)

PMID35461369PMCIDPMC9035150DOI10.1038/s41598-022-10577-2PepBankPUB-35461369

Summary

Body weight loss of ≥ 10% improves the metabolic derangements and liver disease in the majority of non-alcoholic steatohepatitis (NASH) patients, suggesting metabolic modulators may be effective in controlling disease. The pharmacodynamics of ALT-801, a GLP-1/glucagon receptor dual agonist optimized for NASH and weight loss, were compared to semaglutide (GLP-1 receptor agonist) and elafibranor (peroxisome proliferator-activated receptor, PPAR-α/δ, agonist) in a biopsy-confirmed, diet-induced obese (DIO) mouse model of NASH (DIO-NASH). Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks. Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet. Study endpoints included body and liver weight, liver and plasma total cholesterol and triglycerides, plasma aminotransferases, histological analysis of liver steatosis, inflammation (galectin-3) and fibrosis (collagen type 1 alpha 1), and evaluation of individual animal changes in composite Non-alcoholic Fatty Liver Disease Activity Score (NAS), and fibrosis stage. ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor. ALT-801 significantly reduced the inflammation marker galectin-3 and the fibrosis marker collagen type 1 alpha 1 vs. vehicle (p < 0.05), with ALT-801 producing greater reductions in galectin-3 vs. elafibranor (p < 0.05). Importantly, all animals treated with ALT-801 significantly improved composite NAS compared to the active controls. This study provides evidence for a potential role for ALT-801 in the therapeutic treatment of NASH.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study17

17 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 reduced body weight by approximately 25%, more than semaglutide.
In plain wordsIn mice, ALT-801 reduced body weight more than semaglutide.
Peptide
Pemvidutide
Outcome
DecreaseBody weight versus semaglutide
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
semaglutide
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor.
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136901
02AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 reduced body weight by approximately 25%, more than elafibranor.
In plain wordsIn mice, ALT-801 reduced body weight more than elafibranor.
Peptide
Pemvidutide
Outcome
DecreaseBody weight versus elafibranor
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
elafibranor
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor.
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136902
03AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 reduced plasma aminotransferases more than semaglutide.
In plain wordsIn mice, ALT-801 reduced plasma liver enzymes more than semaglutide.
Peptide
Pemvidutide
Outcome
DecreasePlasma aminotransferases versus semaglutide
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
semaglutide
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor.
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136903
04AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 reduced plasma aminotransferases more than elafibranor.
In plain wordsIn mice, ALT-801 reduced plasma liver enzymes more than elafibranor.
Peptide
Pemvidutide
Outcome
DecreasePlasma aminotransferases versus elafibranor
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
elafibranor
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor.
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136904
05AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 reduced plasma total cholesterol more than semaglutide.
In plain wordsIn mice, ALT-801 reduced blood cholesterol more than semaglutide.
Peptide
Pemvidutide
Outcome
DecreasePlasma total cholesterol versus semaglutide
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
semaglutide
Outcome group
Lipids · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor.
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136905
06AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 reduced plasma total cholesterol more than elafibranor.
In plain wordsIn mice, ALT-801 reduced blood cholesterol more than elafibranor.
Peptide
Pemvidutide
Outcome
DecreasePlasma total cholesterol versus elafibranor
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
elafibranor
Outcome group
Lipids · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor.
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136906
07AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 reduced liver triglycerides more than semaglutide.
In plain wordsIn mice, ALT-801 reduced liver triglycerides more than semaglutide.
Peptide
Pemvidutide
Outcome
DecreaseLiver triglycerides versus semaglutide
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
semaglutide
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor.
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136907
08AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 reduced liver triglycerides more than elafibranor.
In plain wordsIn mice, ALT-801 reduced liver triglycerides more than elafibranor.
Peptide
Pemvidutide
Outcome
DecreaseLiver triglycerides versus elafibranor
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
elafibranor
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor.
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136908
09AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 reduced liver total cholesterol more than semaglutide.
In plain wordsIn mice, ALT-801 reduced liver cholesterol more than semaglutide.
Peptide
Pemvidutide
Outcome
DecreaseLiver total cholesterol versus semaglutide
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
semaglutide
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor.
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136909
10AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 reduced liver total cholesterol more than elafibranor.
In plain wordsIn mice, ALT-801 reduced liver cholesterol more than elafibranor.
Peptide
Pemvidutide
Outcome
DecreaseLiver total cholesterol versus elafibranor
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
elafibranor
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor.
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136910
11AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 improved liver steatosis more than semaglutide.
In plain wordsIn mice, ALT-801 reduced liver fat accumulation more than semaglutide.
Peptide
Pemvidutide
Outcome
DecreaseLiver steatosis versus semaglutide
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
semaglutide
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor.
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136911
12AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 improved liver steatosis more than elafibranor.
In plain wordsIn mice, ALT-801 reduced liver fat accumulation more than elafibranor.
Peptide
Pemvidutide
Outcome
DecreaseLiver steatosis versus elafibranor
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
elafibranor
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 demonstrated significant reductions in body weight (approx. 25%), plasma aminotransferases, plasma total cholesterol and liver triglycerides/total cholesterol in conjunction with improved liver steatosis, with greater reductions (p < 0.05) compared to semaglutide and elafibranor.
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136912
13AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 significantly reduced galectin-3 versus vehicle.
In plain wordsIn mice, ALT-801 reduced galectin-3 compared with vehicle.
Peptide
Pemvidutide
Outcome
DecreaseGalectin-3 versus vehicle
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
vehicle
Outcome group
Inflammation markers · Liver
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 significantly reduced the inflammation marker galectin-3 and the fibrosis marker collagen type 1 alpha 1 vs. vehicle (p < 0.05), with ALT-801 producing greater reductions in galectin-3 vs. elafibranor (p < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136913
14AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 significantly reduced collagen type 1 alpha 1 versus vehicle.
In plain wordsIn mice, ALT-801 reduced a fibrosis marker compared with vehicle.
Peptide
Pemvidutide
Outcome
DecreaseCollagen type 1 alpha 1
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
vehicle
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 significantly reduced the inflammation marker galectin-3 and the fibrosis marker collagen type 1 alpha 1 vs. vehicle (p < 0.05), with ALT-801 producing greater reductions in galectin-3 vs. elafibranor (p < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136914
15AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, ALT-801 reduced galectin-3 more than elafibranor.
In plain wordsIn mice, ALT-801 reduced galectin-3 more than elafibranor.
Peptide
Pemvidutide
Outcome
DecreaseGalectin-3 versus elafibranor
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
elafibranor
Outcome group
Inflammation markers · Liver
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
ALT-801 significantly reduced the inflammation marker galectin-3 and the fibrosis marker collagen type 1 alpha 1 vs. vehicle (p < 0.05), with ALT-801 producing greater reductions in galectin-3 vs. elafibranor (p < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136915
16AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, all ALT-801-treated animals significantly improved composite NAS compared with semaglutide.
In plain wordsIn mice, ALT-801 improved the composite liver disease score compared with semaglutide.
Peptide
Pemvidutide
Outcome
DecreaseComposite NAS versus semaglutide
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
semaglutide
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
Importantly, all animals treated with ALT-801 significantly improved composite NAS compared to the active controls.
3 context sentences(design, population, supporting numbers)
Summary · context
The pharmacodynamics of ALT-801, a GLP-1/glucagon receptor dual agonist optimized for NASH and weight loss, were compared to semaglutide (GLP-1 receptor agonist) and elafibranor (peroxisome proliferator-activated receptor, PPAR-α/δ, agonist) in a biopsy-confirmed, diet-induced obese (DIO) mouse model of NASH (DIO-NASH).
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136916
17AnimalAnimal study (in vivo)Efficacy outcome
In mice with NASH, all ALT-801-treated animals significantly improved composite NAS compared with elafibranor.
In plain wordsIn mice, ALT-801 improved the composite liver disease score compared with elafibranor.
Peptide
Pemvidutide
Outcome
DecreaseComposite NAS versus elafibranor
Study
mousen: not reported in source
diet-induced obese NASH
Comparator
elafibranor
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · 12 weeksAs given in this study (mouse).
Source sentences
Summary
Importantly, all animals treated with ALT-801 significantly improved composite NAS compared to the active controls.
3 context sentences(design, population, supporting numbers)
Summary · context
The pharmacodynamics of ALT-801, a GLP-1/glucagon receptor dual agonist optimized for NASH and weight loss, were compared to semaglutide (GLP-1 receptor agonist) and elafibranor (peroxisome proliferator-activated receptor, PPAR-α/δ, agonist) in a biopsy-confirmed, diet-induced obese (DIO) mouse model of NASH (DIO-NASH).
Summary · context
Male C57BL/6J mice were fed Amylin Liver NASH (AMLN) diet for 32 weeks.
Summary · context
Animals with biopsy-confirmed steatosis and fibrosis received ALT-801, semaglutide, elafibranor, or vehicle daily for 12 weeks while maintained on the AMLN diet.
Show in the study text Report a problemFND-3546136917

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 3Current
27 Oct 2026, 18:20 UTC
Study results updated
Version 2
27 Oct 2026, 16:32 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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