Retatrutide Cardiometabolic Markers: What Clinical Trials Measured

PBIPeptide Bio Index Editorial DeskSource-labeled research summary

Source-labeled9 min readUpdated Sep 6, 2026

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Trials and study designs that reported cardiometabolic markers
Body weight outcomes reported
Body composition: fat mass and lean mass assessments
Liver fat (hepatic steatosis) outcomes
Glycemia and other metabolic measures
Cardiac and vital-sign measurements
Safety and adverse events captured
What the reviewed sources did not report or reported incompletely
Reported study-design details from cited sources
Limitations and research gaps
Documentation checklist
Related research supplies
More Retatrutide research
Sources and references

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This article summarizes published research and reported study designs. It is not medical advice, dosing guidance, or a personal-use recommendation.

This evidence deep dive summarizes which cardiometabolic markers were measured in clinical trials of retatrutide (LY3437943) and how those markers were reported in the reviewed phase 2 trials and related publications.

Trials and study designs that reported cardiometabolic markers

The reviewed clinical evidence base includes randomized, double-blind, placebo-controlled phase 2 trials that measured cardiometabolic outcomes: a 48-week obesity trial that specified percent change in body weight at 24 weeks as the primary end point (adults with BMI ≥30 or BMI 27–<30 plus a weight-related condition) (S1); a randomized phase 2a substudy focused on participants with metabolic dysfunction-associated steatotic liver disease and ≥10% liver fat drawn from the obesity trial population (S2); and a phase 2, double-blind, parallel-group randomized substudy in adults with type 2 diabetes that prespecified percent change in total body fat mass by DXA at week 36 (S8). ^{[S1] [S2] [S8]}

Body weight outcomes reported

Percent change in body weight was a primary or key efficacy outcome across the obesity-phase 2 program: the phase 2 obesity trial reported least-squares mean percent changes at 24 weeks of -7.2% (1 mg), -12.9% (combined 4 mg), -17.3% (combined 8 mg), and -17.5% (12 mg) versus -1.6% with placebo, and at 48 weeks of -8.7% (1 mg), -17.1% (4 mg), -22.8% (8 mg), and -24.2% (12 mg) versus -2.1% with placebo (S1). A contemporary systematic review of RCTs included the reported weight-loss magnitude for retatrutide 12 mg (up to ~22.1% at 48 weeks) as part of aggregated weight-loss comparisons across agents (S3). ^{[S1] [S3]}

Body composition: fat mass and lean mass assessments

A dedicated substudy in adults with type 2 diabetes measured percent change in total body fat mass by dual-energy X-ray absorptiometry (DXA) as the prespecified primary substudy end point at week 36, reporting dose-dependent reductions in total fat mass (e.g., 15.2% with pooled 4 mg, 26.1% with pooled 8 mg, and 23.2% with 12 mg) and least-squares mean differences versus placebo (for example, -21.6% for pooled 8 mg versus placebo) (S8). The substudy also reported that the proportion of lean-mass loss relative to total weight loss was similar to other obesity treatments (S8). ^[S8]

Liver fat (hepatic steatosis) outcomes

In a randomized phase 2a trial of participants with metabolic dysfunction-associated steatotic liver disease, retatrutide dose groups (1, 4, 8, 12 mg once weekly) showed mean relative changes from baseline in liver fat at 24 weeks of -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), and -82.4% (12 mg) versus +0.3% for placebo; the trial also reported the proportion of participants reaching 'normal' liver fat (<5%) at 24 weeks (e.g., 79% at 8 mg, 86% at 12 mg) (S2). The publication further noted that liver-fat reductions were significantly related to changes in body weight, abdominal fat, and metabolic measures linked to insulin sensitivity and lipid metabolism (S2). ^[S2]

Glycemia and other metabolic measures

Trials and reviews reported glucose and broader metabolic outcomes alongside bodyweight and body-composition changes: the type 2 diabetes substudy enrolled adults with HbA1c 7.0–10.5% and described retatrutide as demonstrating robust glucose reductions in addition to bodyweight effects (S8). A narrative review summarized phase 1/2 clinical results as showing reductions in glycated hemoglobin (HbA1c) and improvements in liver steatosis and diabetic kidney disease across the clinical program (S5). The liver-fat substudy reported that liver-fat reductions correlated with changes in metabolic measures associated with improved insulin sensitivity and lipid metabolism, though specific lipid or insulin metrics are not detailed in the reviewed excerpt (S2). ^{[S8] [S5] [S2]}

Cardiac and vital-sign measurements

Vital-sign monitoring reported dose-dependent increases in heart rate in the phase 2 obesity trial, with heart-rate increases peaking at 24 weeks and declining thereafter; heart-rate effects were included among safety assessments (S1). ^[S1]

Safety and adverse events captured

Across trials and reviews, adverse events were frequently reported and were predominantly gastrointestinal in nature and dose-related (nausea, vomiting, diarrhea, constipation); the phase 2 obesity trial emphasized dose-related gastrointestinal events that were mostly mild to moderate and partially mitigated by a lower starting dose, and the type 2 diabetes substudy reported similar frequencies of adverse events with gastrointestinal events being most common and no deaths reported (S1, S8). A systematic review of RCTs summarized that gastrointestinal adverse events were a common class effect among incretin-based agents (S3). ^{[S1] [S3] [S8]}

What the reviewed sources did not report or reported incompletely

Detailed trial-level results for some cardiometabolic measures are not provided in the reviewed excerpts: for example, specific numeric changes in standard lipid-panel components (LDL-C, HDL-C, triglycerides) are not reported in the reviewed excerpts, and exact HbA1c change magnitudes were not included in the provided substudy excerpt (S1, S2, S8). Blood-pressure trajectories and comprehensive renal or cardiovascular event outcomes are not documented in the reviewed excerpts (S1, S2, S8). ^{[S1] [S2] [S8]}

Reported study-design details from cited sources

The following table summarizes protocol details reported in cited studies. These details are provided as literature context only and are not recommendations or instructions.

Source	Study Type	Model / Subject	Amount Reported	Route Reported	Frequency	Duration	Notes
[S1]	Phase 2, double-blind, randomized, placebo-controlled trial	Adults with obesity (BMI ≥30 or BMI 27–	1 mg, 4 mg (two starting-dose regimens reported), 8 mg (two starting-dose regimens reported), 12 mg (starting dose 2 mg reported)	subcutaneous	once weekly	48 weeks	Primary end point: percent change in body weight from baseline to 24 weeks; multiple dose cohorts (1 mg, 4 mg [initial dose 2 mg or 4 mg], 8 mg [initial dose 2 mg or 4 mg], 12 mg [initial dose 2 mg]).
[S2]	Randomized, double-blind, placebo-controlled phase 2a trial	Participants with metabolic dysfunction-associated steatotic liver disease and ≥10% liver fat (subset of obesity trial population)	1 mg, 4 mg, 8 mg, 12 mg	subcutaneous	once weekly	48 weeks (primary liver-fat change reported at 24 weeks)	Primary hepatic objective reported as mean relative change in liver fat at 24 weeks across dose groups.
[S8]	Phase 2, double-blind, parallel-group, placebo-controlled, randomized substudy	Adults with type 2 diabetes (HbA1c 7.0–10.5%, BMI 25–50 kg/m2)	0.5 mg, 4 mg (pooled starting-dose groups), 8 mg (pooled starting-dose groups), 12 mg; dulaglutide 1.5 mg comparator	subcutaneous	once weekly	36 weeks (body-composition substudy primary end point at week 36)	Prespecified primary substudy end point: percent change from baseline to week 36 in total fat mass by DXA; multiple retatrutide doses and a dulaglutide 1.5 mg comparator arm were included.

Limitations and research gaps

This deep dive is limited to the provided reviewed excerpts and does not include the full trial publications or supplementary materials; additional marker details may appear in the full papers or trial registries.
Most clinical evidence available in the reviewed sources is from phase 2 randomized trials and a narrative/systematic review; long-term outcomes, cardiovascular event endpoints, and phase 3 registration results are not covered in the reviewed excerpts.
Where the reviewed excerpts did not provide numeric results for specific biomarkers (for example, detailed lipid panels or exact HbA1c changes), the entry above states that such details were not reported in the reviewed source.

Documentation checklist

Confirm which trials enrolled adults with overweight or obesity and which enrolled people with type 2 diabetes (S1, S8).
Verify that percent change in body weight was the primary end point at 24 weeks in the phase 2 obesity trial (S1).
Confirm that liver fat (relative change from baseline) at 24 weeks was the prespecified hepatic end point in the MDASLD substudy (S2).
Check that total body fat mass by DXA and the prespecified substudy end point at week 36 were reported in the type 2 diabetes substudy (S8).
Note that heart-rate increases were measured and reported as dose-dependent with a peak at 24 weeks (S1).
Review the reported adverse-event profile with emphasis on dose-related gastrointestinal events across trials (S1, S3, S8).

Dual-energy X-ray absorptiometry (DXA) scanner — operator and calibration documentation (used in the body-composition substudy) (referenced in S8).
Imaging core reporting tools for liver-fat quantification (trial imaging/logistics documentation) (related to liver-fat outcomes in S2).
Calibrated vital-sign monitors and heart-rate recording logs (used for heart-rate measurements reported in S1).

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Sources and references

Peptide Bio Index is affiliated with SourcePoint Research. Articles may link to SourcePointResearch.com and third-party affiliate products. As an Amazon Associate, Peptide Bio Index earns from qualifying purchases. Content is educational and research-literature focused only and is not medical advice, dosing guidance, or a personal-use recommendation.