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Mounjaro ® (tirzepatide) injection
2.5 mg/5 mg/7.5 mg/10 mg/12.5 mg/15 mg
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What were the effects of Mounjaro® (tirzepatide) on the liver, abdominal adipose tissue, and muscle fat content in the SURPASS-3 MRI Substudy?
In the SURPASS-3 MRI substudy, tirzepatide was associated with changes in liver fat content, abdominal adipose tissue, and muscle fat infiltration in adults with type 2 diabetes. Mounjaro is not indicated for weight loss; individual results may vary.
See important safety information, including boxed warning, in the attached prescribing information.
Content Overview
SURPASS-3 MRI Substudy
Mounjaro (tirzepatide) is a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D) for once-weekly, subcutaneous administration.1
SURPASS-3 was a 52-week, phase 3, open-label study of tirzepatide 5, 10, and 15 mg once weekly compared with titrated insulin degludec daily in 1444 adults with T2D inadequately controlled on metformin with or without a sodium-glucose cotransporter-2 (SGLT-2) inhibitor.2
SURPASS-3 MRI Substudy Design
A substudy of the SURPASS-3 trial, SURPASS-3 MRI, was conducted in 296 participants. The primary objective of the substudy was to compare the effect of tirzepatide on the change from baseline in the percentage of liver fat content (LFC) as measured by magnetic resonance imaging (MRI) techniques at 52 weeks, using data pooled from 10 mg and 15 mg dosing arms versus insulin degludec in a subpopulation with high likelihood of liver steatosis.3
The substudy population had a fatty liver index (FLI) >60 at baseline and were on stable doses of metformin with or without an SGLT-2 inhibitor. Baseline characteristics of the substudy are shown in Baseline Demographics and Clinical Characteristics in SURPASS-3 MRI Substudy.3
Parameter |
TZP 5 mg |
TZP 10 mg |
TZP 15 mg |
IDeg |
Total |
Age (years) |
56.5±10.3 |
55.6±9.6 |
56.5±10.0 |
56.5±9.5 |
56.2±9.8 |
Female, n (%) |
27 (38) |
38 (48) |
25 (35) |
34 (46) |
124 (42) |
Duration of diabetes (years) |
7.9±6.0 |
9.4±8.2 |
8.7±6.7 |
7.0±4.8 |
8.3±6.6 |
HbA1c (%) |
8.27±0.89 |
8.41±0.90 |
8.15±0.87 |
8.14±0.99 |
8.24±0.92 |
On metformin + SGLT-2i, n (%) |
24 (34) |
25 (32) |
23 (32) |
16 (22) |
88 (30) |
BMI (kg/m2) |
34.5±5.3 |
33.1±4.6 |
33.4±4.5 |
33.0±4.9 |
33.5±4.8 |
Body weight (kg) |
98.0±18.3 |
93.1±14.0 |
95.6±16.0 |
91.2±16.6 |
94.4±16.3 |
Abbreviations: BMI = body mass index; HbA1c = glycated hemoglobin; IDeg = insulin degludec; MRI = magnetic resonance imaging; SGLT-2i = sodium-glucose co-transporter-2 inhibitor; TZP = tirzepatide.
Effect of Tirzepatide on Liver Fat Content and Liver Function Tests in SURPASS-3 MRI
Primary objective of the substudy was to compare the effect of tirzepatide on the change from baseline in the percentage of LFC at 52 weeks, using data pooled from 10 mg and 15 mg dosing arms, versus insulin degludec.3
Relative change from baseline in LFC at week 52 was
- –29.78% with tirzepatide 5 mg
- –47.11% with tirzepatide 10 mg
- –39.59% with tirzepatide 15 mg, and
- –11.17% with insulin degludec (p<.05 vs insulin degludec for tirzepatide 5mg and p<.001 vs insulin degludec for tirzepatide 10 and 15 mg; Liver Fat Content).3
Please refer to Liver Fat Content for the proportion of participants at week 52 with
- LFC ≤10%, and
- ≥30% relative decrease from baseline in LFC.
TZP 5 mg |
TZP 10 mg |
TZP 15 mg |
IDeg |
|
LFC baseline, % |
14.86 (1.11) |
14.78 (1.04) |
16.65 (1.09) |
16.58 (1.05) |
LFC endpoint, % |
10.11 (0.80)* |
8.16 (0.79)** |
8.59 (0.77)** |
13.18 (0.79) |
Relative change in LFC from baseline, % |
-29.78 (5.61)* |
-47.11 (5.58)** |
-39.59 (5.42)** |
-11.17 (5.58) |
Proportion of participants with LFC ≤10% |
||||
Baseline |
32.58 (5.81) |
38.00 (5.64) |
19.85 (4.87) |
29.45 (5.37) |
Endpoint |
60.42 (7.98)* |
77.86 (6.41)** |
73.92 (6.69)** |
34.79 (7.87) |
Proportion of participants with ≥30% relative decrease in LFC |
66.94 (7.39)* |
81.41 (5.62)** |
78.77 (5.97)** |
32.12 (7.19) |
Abbreviations: IDeg = insulin degludec; LFC = liver fat content; LOCF = last observation carried forward; mITT = modified intention-to-treat; MRI = magnetic resonance imaging; TZP = tirzepatide.
Notes: *p<.05 and **p<.001 are based on percent change from baseline versus IDeg; not controlled for multiplicity adjustment.
Note: TZP doses were achieved through stepwise 2.5 mg dose escalation every 4 weeks. IDeg starting dose was 10 U/day and titrated to an FSG <5 mmol/L following a treat-to-target algorithm. Mean IDeg dose was 58.8 U/day at 52 weeks.
aData are estimates (SE) mITT-efficacy analysis set unless otherwise noted: on treatment data prior to initiating rescue therapy from mITT population excluding patients with baseline and postbaseline data not obtained or not valid. N values vary across primary and secondary endpoints at week 52.
bMissing values at week 52 were imputed with LOCF using mITT efficacy analysis set (if early termination or unscheduled visit with MRI scan available).
A secondary objective of the substudy was to compare each dose of tirzepatide with insulin degludec at 52 weeks for liver function tests (see Liver Function Tests Results).3
Parametera |
TZP 5 mg |
TZP 10 mg |
TZP 15 mg |
IDeg |
ALT, U/L |
||||
Baseline |
28.0 (1.7) |
25.8 (1.5) |
26.1 (1.6) |
24.7 (1.5) |
Endpoint |
21.8 (1.1) |
19.1 (1.0)* |
17.8 (0.9)** |
22.8 (1.2) |
AST, U/L |
||||
Baseline |
20.7 (1.0) |
19.6 (0.9) |
20.6 (1.0) |
20.0 (1.0) |
Endpoint |
18.3 (0.8) |
17.8 (0.7)* |
16.5 (0.7)** |
20.4 (0.9) |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; IDeg = insulin degludec; mITT = modified intention-to-treat; MRI = magnetic resonance imaging; TZP = tirzepatide.
*p<.05 and **p<.001 versus IDeg; not controlled for multiplicity adjustement.
Note: TZP doses were achieved through stepwise 2.5 mg dose escalation every 4 weeks. IDeg starting dose was 10 U/day and titrated to an FSG <5 mmol/L following a treat-to-target algorithm. Mean IDeg dose was 58.8 U/day at 52 weeks.
aData are estimates (SE) mITT safety analysis set: All available data from mITT population including safety follow-up regardless of adherence to the study drug or use of rescue therapy including patients with nonmissing baseline and at least 1 nonmissing postbaseline record. N values vary across primary and secondary endpoints at week 52.
Effect of Tirzepatide on Abdominal Adipose Tissue in SURPASS-3 MRI
Secondary objectives included comparison of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes of the individual tirzepatide doses versus insulin degludec at week 52.3
Changes in VAT and ASAT volumes in participants treated with tirzepatide and insulin degludec at week 52 can be found in Measures of Abdominal Visceral and Subcutaneous Adipose Tissue.
TZP 5 mg |
TZP 10 mg |
TZP 15 mg |
IDeg |
|
VAT (L) |
||||
Baseline |
6.87 (0.24) |
6.21 (0.23) |
6.81 (0.24) |
6.34 (0.23) |
Endpoint |
5.42 (0.19)** |
5.00 (0.18)** |
4.88 (0.18)** |
6.90 (0.18) |
ASAT (L) |
||||
Baseline |
10.99 (0.51) |
10.21 (0.49) |
10.34 (0.50) |
10.04 (0.49) |
Endpoint |
9.07 (0.25)** |
8.22 (0.24)** |
8.42 (0.23)** |
11.10 (0.24) |
Abbreviations: ASAT = abdominal subcutaneous adipose tissue; VAT = visceral adipose tissue; IDeg = insulin degludec; LOCF = last observation carried forward; mITT = modified intention-to-treat; MRI = magnetic resonance imaging; TZP = tirzepatide.
**p<.001 versus IDeg; not controlled for multiplicity adjustment
Note: TZP doses were achieved through stepwise 2.5 mg dose escalation every 4 weeks. IDeg starting dose was 10 U/day and titrated to an FSG <5 mmol/L following a treat-to-target algorithm. Mean IDeg dose was 58.8 U/day at 52 weeks.
aData are estimates (SE), unless otherwise noted: on treatment data prior to initiating rescue therapy from mITT population excluding patients with baseline and postbaseline data not obtained or not valid. N values vary across primary and secondary endpoints at week 52.
bMissing values at week 52 were imputed with LOCF using mITT efficacy analysis set (if early termination or unscheduled visit with MRI scan available).
Post Hoc Analyses From SURPASS-3 MRI
Effect of Tirzepatide on Liver Fat Content and Adipose Tissue in Participants With Normoglycemia in SURPASS-3 MRI Post Hoc Analysis
A post hoc analysis of the SURPASS-3 MRI substudy compared changes in LFC, VAT, and abdominal subcutaneous adipose tissue (ASAT) at week 52 in tirzepatide-treated participants who had normoglycemia (HbA1c <5.7%) and those who did not (HbA1c ≥5.7%).4
The analyses were conducted on pooled data from all tirzepatide arms combined (5, 10, and 15 mg). The analysis excluded participants with missing HbA1c values at week 52. In addition, data after rescue or study drug discontinuation were also excluded.4
Baseline characteristics were mostly similar between participants with HbA1c <5.7% (N=70) and participants with HbA1c ≥5.7% (N=118). However, participants who had normoglycemia, when compared with those who did not have normoglycemia,
- were slightly younger (mean age=53.8 years vs 57.7 years; p=.009)
- had lower baseline mean HbA1c (7.99% vs 8.44%; p<.001), and
- had a higher proportion assigned to tirzepatide 15 mg (44.3% vs 26.3%; p=.026).4
SURPASS-3 MRI Substudy Post Hoc Analysis: Change From Baseline in LFC, VAT, and ASAT in Participants With Normoglycemia Versus Participants Without Normoglycemia at Week 52 presents the change from baseline to week 52 in LFC, VAT, and ASAT in participants with HbA1c <5.7% and HbA1c ≥5.7%.
Figure 1 description: In SURPASS-MRI, in pooled data of all participants treated with tirzepatide, changes from baseline to week 52 in liver fat content, visceral adipose tissue, and abdominal subcutaneous adipose tissue were -10.4%, -2.3% and -2.8% in participants with HbA1c less than 5.7%, and -5.5, -1.0, and -1.4 in participants with HbA1c greater than or equal to 5.7%, respectively.
Abbreviations: ASAT = abdominal subcutaneous adipose tissue; HbA1c = glycated hemoglobin; LFC = liver fat content; LOCF = last observation carried forward; LSM = least squares mean; MRI = magnetic resonance imaging; VAT = visceral adipose tissue.
Note: Statistical analyses were based on analysis of covariance. Missing values were imputed with LOCF.
Effect of Tirzepatide on Muscle Fat in SURPASS-3 MRI Post Hoc Analysis
A post hoc analysis of the SURPASS-3 MRI substudy evaluated change from baseline to week 52 in participants treated with tirzepatide or insulin degludec in
- thigh muscle fat infiltration (MFI)
- fat-free muscle volume (MV), and
- sex-, height-, weight-, and body mass index-invariant MV z-scores (z-MV).5
In SURPASS-3 MRI, neck-to-knee images were collected and analyzed for quantification of thigh MV and MFI using AMRA® Researcher (AMRA Medical AB, Linköping, Sweden).5
Mean baseline MFI, MV, and z-MV were not statistically different between pooled tirzepatide and insulin degludec treatment groups.5
Baseline and Change of Muscle Composition at Week 52 in the SURPASS-3 MRI Study presents the change from baseline at week 52 in participants treated with tirzepatide or insulin degludec in
- MFI
- MV, and
- z-MV.5
Parameter |
TZP Pooled |
TZP 5 mg |
TZP 10 mg |
TZP 15 mg |
IDeg |
Muscle volume, L |
|||||
Baseline, mean (SD) |
10.8 (2.6) |
11.0 (2.8) |
10.3 (2.1) |
11.0 (2.7) |
10.7 (3.1) |
Absolute change |
-0.64 |
-0.44 |
-0.71 |
-0.76 |
0.16 |
Relative change (%) |
-6.0 |
-4.1 |
-6.9 |
-7.0 |
1.6 |
Muscle volume z-score, SD |
|||||
Baseline, mean (SD) |
-0.48 (1.07) |
-0.58 (1.11) |
-0.42 (1.12) |
-0.44 (1.00) |
-0.25 (1.07) |
Absolute change |
-0.22 |
-0.12 |
-0.23 |
-0.30 |
0.06 |
Muscle fat infiltration, % |
|||||
Baseline, mean (SD) |
8.1 (2.3) |
8.1 (2.1) |
8.0 (2.5) |
8.0 (2.3) |
7.6 (2.7) |
Absolute change |
-0.36 |
-0.23 |
-0.42 |
-0.44 |
0.03 |
Relative change (%) |
-4.5 |
-2.6 |
-5.6 |
-5.2 |
0.2 |
Abbreviations: IDeg = insulin degludec; TZP = tirzepatide; MRI = magnetic resonance imaging.
Notes: Data are shown as mean (95% CI) unless otherwise indicated. P-values for change are from paired t-tests; not controlled for multiplicity adjustment.
ap<0.0001 vs baseline.
bp=0.043 vs baseline.
cp=0.023 vs baseline.
dp=0.013 vs baseline.
ep=0.0015 vs baseline.
fp=0.35 vs baseline.
gp=0.042 vs baseline.
hp=0.0002 vs baseline.
ip=0.62 vs baseline.
jp=0.047 vs baseline.
kp=0.83 vs baseline.
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Mounjaro [package insert]. Indianapolis, IN: Eli Lilly and Company; 2025.
2Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;398(10300):583-598. https://doi.org/10.1016/S0140-6736(21)01443-4
3Gastaldelli A, Cusi K, Fernández Landó L, et al. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): A substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 2022;10(6):393-406. https://doi.org/10.1016/S2213-8587(22)00070-5
4Rodríguez Á, Cusi K, Gastaldelli A, et al. Changes in liver and abdominal fat in tirzepatide-treated patients achieving normoglycemia in the SURPASS-3 MRI substudy. Poster presented at: 83rd Scientific Session of the American Diabetes Association; June 23-26, 2023; San Diego, CA, USA.
5Sattar N, Neeland IJ, Dahlqvist Leinhard O, et al. 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. Lancet Diabetes Endocrinol. 2025;13(6):482-493. https://doi.org/10.1016/S2213-8587(25)00027-0
Date of Last Review: May 05, 2025