Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial.

Sattar N, Neeland IJ, Dahlqvist Leinhard O, Fernández Landó L, Bray R, Linge J, Rodriguez A

The lancet. Diabetes & endocrinology30 Apr 2025Cited by 68 (Europe PMC)

PMID40318682DOI10.1016/s2213-8587(25)00027-0PepBankPUB-40318682

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: CC BY-NC-ND. Results still quote short attributed sentences.

Results from this study7

7 results from studies that gave the peptide. 7 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, changes in all three muscle composition variables with pooled tirzepatide differed significantly from those with insulin degludec, which increased muscle volume.
In plain wordsIn adults with type 2 diabetes, tirzepatide changed muscle composition differently from insulin degludec, which slightly increased muscle volume.
Peptide
Tirzepatide
Outcome
DecreaseMuscle composition changes versus insulin degludec
Study
n = 246
Comparator
Insulin degludec
Analysis
Exploratory
Outcome group
Body composition · Musculoskeletal
Studied dose
5, 10 or 15 mg · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
The changes in all three muscle composition variables with pooled tirzepatide were significantly different compared to those with insulin degludec.
3 context sentences(design, population, supporting numbers)
Summary · context
Insulin degludec was associated with a modest and significant increase in bodyweight and muscle volume, but no significant change in the other variables.
Summary · context
The multicentre (45 sites) and multinational (eight countries) MRI substudy of SURPASS-3 enrolled insulin-naive adults (aged ≥18 years) with type 2 diabetes who were on treatment with metformin with or without a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, had an HbA_1c of 7·0-10·5%…
Summary · context
Participants were randomly assigned (1:1:1:1) to receive subcutaneous injection once per week of tirzepatide (5, 10, or 15 mg), or subcutaneous injection once per day of titrated insulin degludec.
Report a problemFND-4031868204
02HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, pooled tirzepatide reduced thigh muscle fat infiltration from baseline to week 52.
In plain wordsIn adults with type 2 diabetes, tirzepatide reduced the fat inside thigh muscle over 52 weeks.
Peptide
Tirzepatide
Outcome
DecreaseThigh muscle fat infiltration change at week 52
Study
n = 190
Comparator
Baseline
Analysis
Exploratory
Outcome group
Body composition · Musculoskeletal
Studied dose
5, 10 or 15 mg · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
muscle fat infiltration (for pooled tirzepatide, mean change -0·36 percentage points [95% CI -0·48 to -0·25], p<0·0001
2 context sentences(design, population, supporting numbers)
Summary · context
The multicentre (45 sites) and multinational (eight countries) MRI substudy of SURPASS-3 enrolled insulin-naive adults (aged ≥18 years) with type 2 diabetes who were on treatment with metformin with or without a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, had an HbA_1c of 7·0-10·5%…
Summary · context
Participants were randomly assigned (1:1:1:1) to receive subcutaneous injection once per week of tirzepatide (5, 10, or 15 mg), or subcutaneous injection once per day of titrated insulin degludec.
Report a problemFND-4031868201
03HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, pooled tirzepatide reduced thigh muscle volume from baseline to week 52, alongside significant weight reduction.
In plain wordsIn adults with type 2 diabetes, tirzepatide lowered thigh muscle volume over 52 weeks, as weight fell.
Peptide
Tirzepatide
Outcome
DecreaseThigh muscle volume change at week 52
Study
n = 190
Comparator
Baseline
Analysis
Exploratory
Outcome group
Body composition · Musculoskeletal
Studied dose
5, 10 or 15 mg · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
muscle volume (-0·64 L [95% CI -0·74 to -0·54], p<0·0001
2 context sentences(design, population, supporting numbers)
Summary · context
The multicentre (45 sites) and multinational (eight countries) MRI substudy of SURPASS-3 enrolled insulin-naive adults (aged ≥18 years) with type 2 diabetes who were on treatment with metformin with or without a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, had an HbA_1c of 7·0-10·5%…
Summary · context
Participants were randomly assigned (1:1:1:1) to receive subcutaneous injection once per week of tirzepatide (5, 10, or 15 mg), or subcutaneous injection once per day of titrated insulin degludec.
Report a problemFND-4031868202
04HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, pooled tirzepatide reduced the thigh muscle volume Z score from baseline to week 52.
In plain wordsIn adults with type 2 diabetes, tirzepatide lowered the thigh muscle volume Z score over 52 weeks.
Peptide
Tirzepatide
Outcome
DecreaseThigh muscle volume Z score change at week 52
Study
n = 190
Comparator
Baseline
Analysis
Exploratory
Outcome group
Body composition · Musculoskeletal
Studied dose
5, 10 or 15 mg · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
muscle volume Z score (-0·22 [95% CI -0·29 to -0·15], p<0·0001
2 context sentences(design, population, supporting numbers)
Summary · context
The multicentre (45 sites) and multinational (eight countries) MRI substudy of SURPASS-3 enrolled insulin-naive adults (aged ≥18 years) with type 2 diabetes who were on treatment with metformin with or without a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, had an HbA_1c of 7·0-10·5%…
Summary · context
Participants were randomly assigned (1:1:1:1) to receive subcutaneous injection once per week of tirzepatide (5, 10, or 15 mg), or subcutaneous injection once per day of titrated insulin degludec.
Report a problemFND-4031868203
05HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, muscle volume changes with pooled tirzepatide were similar to population-based estimates for the same weight change.
In plain wordsIn adults with type 2 diabetes, tirzepatide muscle volume loss was similar to what is expected for the weight lost in the general population.
Peptide
Tirzepatide
Outcome
No significant changeMuscle volume change versus population-based estimate
Study
n = 190
Comparator
Population-based estimate (UK Biobank)
Analysis
Exploratory
Outcome group
Body composition · Musculoskeletal
Studied dose
5, 10 or 15 mg · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
observed muscle volume changes across all tirzepatide doses were similar to population-based estimated changes (for pooled tirzepatide, mean difference vs population-based estimate, -0·04 L [95% CI -0·11 to 0·03], p=0·22
2 context sentences(design, population, supporting numbers)
Summary · context
The multicentre (45 sites) and multinational (eight countries) MRI substudy of SURPASS-3 enrolled insulin-naive adults (aged ≥18 years) with type 2 diabetes who were on treatment with metformin with or without a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, had an HbA_1c of 7·0-10·5%…
Summary · context
Participants were randomly assigned (1:1:1:1) to receive subcutaneous injection once per week of tirzepatide (5, 10, or 15 mg), or subcutaneous injection once per day of titrated insulin degludec.
Report a problemFND-4031868205
06HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, reductions in muscle fat infiltration with pooled tirzepatide were significantly greater than population-based estimates.
In plain wordsIn adults with type 2 diabetes, tirzepatide reduced muscle fat more than expected for the weight lost in the general population.
Peptide
Tirzepatide
Outcome
DecreaseMuscle fat infiltration reduction versus population-based estimate
Study
n = 190
Comparator
Population-based estimate (UK Biobank)
Analysis
Exploratory
Outcome group
Body composition · Musculoskeletal
Studied dose
5, 10 or 15 mg · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
observed reductions in muscle fat infiltration across all doses were significantly greater than population-based estimates (for pooled tirzepatide, mean difference -0·42 percentage points [95% CI -0·54 to -0·31], p<0·0001
2 context sentences(design, population, supporting numbers)
Summary · context
The multicentre (45 sites) and multinational (eight countries) MRI substudy of SURPASS-3 enrolled insulin-naive adults (aged ≥18 years) with type 2 diabetes who were on treatment with metformin with or without a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, had an HbA_1c of 7·0-10·5%…
Summary · context
Participants were randomly assigned (1:1:1:1) to receive subcutaneous injection once per week of tirzepatide (5, 10, or 15 mg), or subcutaneous injection once per day of titrated insulin degludec.
Report a problemFND-4031868206
07HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, the reduction in muscle volume Z score with tirzepatide 15 mg was significantly greater than the population-based estimate.
In plain wordsIn adults with type 2 diabetes, tirzepatide 15 mg lowered the muscle volume Z score more than expected for weight lost in the general population.
Peptide
Tirzepatide
Outcome
DecreaseMuscle volume Z score reduction versus population-based estimate (15 mg)
Study
n = 67
Comparator
Population-based estimate (UK Biobank)
Analysis
Exploratory
Outcome group
Body composition · Musculoskeletal
Studied dose
15 mg · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
the observed reduction in muscle volume Z score with tirzepatide 15 mg was significantly greater than the population-based estimate (mean difference -0·18 [95% CI -0·29 to -0·07], p=0·0016
2 context sentences(design, population, supporting numbers)
Summary · context
The multicentre (45 sites) and multinational (eight countries) MRI substudy of SURPASS-3 enrolled insulin-naive adults (aged ≥18 years) with type 2 diabetes who were on treatment with metformin with or without a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, had an HbA_1c of 7·0-10·5%…
Summary · context
Participants were randomly assigned (1:1:1:1) to receive subcutaneous injection once per week of tirzepatide (5, 10, or 15 mg), or subcutaneous injection once per day of titrated insulin degludec.
Report a problemFND-4031868207

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

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT03882970

A Study of Tirzepatide (LY3298176) Versus Insulin Degludec in Participants With Type 2 Diabetes

Eli Lilly and Companyn = 1,4441 Apr 2019 to 4 Jan 2021

Type 2 Diabetes Mellitus

Trial page ClinicalTrials.govUpdated 19 Jan 2022

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

Terms as the source lists them.

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