Beyond Weight Loss: Comparative Effects of Tirzepatide Plus Low-Energy Ketogenic Versus Low-Calorie Diet on Hepatic Steatosis and Stiffness in MASLD.

Schiavo L, Santella B, Mingo M, Rossetti G, Orio M, Pilone V

Nutrients24 Jul 2025Cited by 9 (Europe PMC)

PMID40805994PMCIDPMC12348380DOI10.3390/nu17152409PepBankPUB-40805994

Summary

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the liver fat content in patients with obesity and T2D. However, its effect on liver-specific outcomes such as steatosis and fibrosis remains incompletely characterized. Low-energy ketogenic therapy (LEKT), a nutritional strategy characterized by carbohydrate restriction and nutritional ketosis, may enhance hepatic β-oxidation and reduce hepatic lipogenesis. To date, however, the combination of TZP and LEKT has not been studied in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the hepatic and metabolic effects of TZP combined with either LEKT or a conventional low-calorie diet (LCD) over a 12-week period. Methods: Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group. As primary endpoints, the controlled attenuation parameter (CAP, an index of hepatic steatosis) and liver stiffness measurement (LSM, an index of liver fibrosis) were assessed at the baseline and after 12 weeks using FibroScan^®. Secondary outcomes included changes in body mass index (BMI), glycated hemoglobin (HbA1c), and liver enzymes. Adherence to both diet and pharmacological treatment, as well as tolerability, were systematically monitored throughout the intervention period. Results: Both groups showed significant reductions in body weight (TZP + LEKT, p = 0.0289; TZP + LCD, p = 0.0278), with no significant intergroup difference (p = 0.665). CAP and LSM improved significantly in both groups, but reductions were greater in the TZP + LEKT group (CAP -12.5%, p p p = 0.014; LSM -9.2%, p = 0.022). Between-group differences were statistically significant for both CAP (p = 0.01) and LSM (p = 0.03). Conclusions: Based on these preliminary findings, we support the hypothesis that the combination of TZP and LEKT may be superior to TZP with an LCD in reducing hepatic steatosis and stiffness in individuals with obesity.

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

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Tirzepatide.

01HumanNot a test of Tirzepatide aloneNon-randomized trialEfficacy outcome
In adults with MASLD, tirzepatide with a low-energy ketogenic diet reduced CAP more than tirzepatide with a low-calorie diet (-12.5% vs -6.7%).
In plain wordsIn adults with fatty liver disease, tirzepatide with a ketogenic diet cut liver fat score more than tirzepatide with a low-calorie diet.
Peptide
Tirzepatide
Outcome
DecreaseControlled attenuation parameter (hepatic steatosis)
Study
n = 60
Comparator
Tirzepatide plus low-calorie diet
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Measurements
CAP change
−12.5%
tirzepatide + LEKT
CAP change
−6.7%
tirzepatide + LCD
Source sentences
Summary
CAP and LSM improved significantly in both groups, but reductions were greater in the TZP + LEKT group (CAP -12.5%, p p p = 0.014; LSM -9.2%, p = 0.022).
2 context sentences(design, population, supporting numbers)
Summary · context
Between-group differences were statistically significant for both CAP (p = 0.01) and LSM (p = 0.03).
Summary · context
Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4080599402
02HumanNot a test of Tirzepatide aloneNon-randomized trialEfficacy outcome
In adults with MASLD, tirzepatide with a low-energy ketogenic diet reduced liver stiffness more than tirzepatide with a low-calorie diet (-22.7% vs -9.2%).
In plain wordsIn adults with fatty liver disease, tirzepatide with a ketogenic diet cut liver stiffness more than tirzepatide with a low-calorie diet.
Peptide
Tirzepatide
Outcome
DecreaseLiver stiffness measurement (hepatic fibrosis index)
Study
n = 60
Comparator
Tirzepatide plus low-calorie diet
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Measurements
LSM change
−22.7%
tirzepatide + LEKT
LSM change
−9.2%
tirzepatide + LCD
Source sentences
Summary
CAP and LSM improved significantly in both groups, but reductions were greater in the TZP + LEKT group (CAP -12.5%, p p p = 0.014; LSM -9.2%, p = 0.022).
2 context sentences(design, population, supporting numbers)
Summary · context
Between-group differences were statistically significant for both CAP (p = 0.01) and LSM (p = 0.03).
Summary · context
Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4080599403
03HumanNot a test of Tirzepatide aloneNon-randomized trialEfficacy outcome
In adults with MASLD, 12 weeks of tirzepatide with a low-energy ketogenic diet or with a low-calorie diet both reduced body weight, with no significant difference between the two regimens.
In plain wordsIn adults with fatty liver disease on tirzepatide, both diet plans led to weight loss, and neither diet plan was better for weight.
Peptide
Tirzepatide
Outcome
No significant changeBody weight reduction, tirzepatide plus LEKT versus tirzepatide plus LCD
Study
n = 60
Comparator
Tirzepatide plus low-calorie diet
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
Both groups showed significant reductions in body weight (TZP + LEKT, p = 0.0289; TZP + LCD, p = 0.0278), with no significant intergroup difference (p = 0.665).
1 context sentence(design, population, supporting numbers)
Summary · context
Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4080599401

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 2Current
12 Oct 2026, 12:58 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

Subjects

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