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Study · Randomized controlled trial · n = 282 · 2026

4 results

Retatrutide and lipid and metabolite profiles in participants with obesity with or without type 2 diabetes.

Pearson MJ, Willency JA, Lin Y, Abadi A, Hartman ML, Coskun T, Ruotolo G, Duffin KL, Haupt A, Newgard CB, Pirro V

The Journal of clinical endocrinology and metabolism1 Oct 2026Cited by 1 (Europe PMC)

PMID42135195 (opens in a new tab)PMCIDPMC13671771 (opens in a new tab)DOI10.1210/clinem/dgag201 (opens in a new tab)PepBankPUB-42135195
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Summary

ContextIn phase 2 trials, retatrutide reduced body weight, hemoglobin A1c and improved the lipid profiles of participants living with obesity, with and without T2D.ObjectiveAssess plasma metabolome and lipidome changes associated with retatrutide treatment.MethodsMetabolomics and lipidomics were performed in fasting samples from 2 randomized, placebo-controlled phase 2 trials as a post hoc exploratory analysis. Participants living with obesity with and without T2D were treated for 36 and 48 weeks, respectively. There were 282 and 213 participants in the obesity and T2D trials, respectively and the intervention(s) received were: Obesity trial: retatrutide (1, 4, 8, and 12 mg) or placebo; T2D trial: retatrutide (0.5, 4, 8, and 12 mg) or placebo or dulaglutide (1.5 mg). The main outcome measure(s) were changes in metabolite and lipid levels with retatrutide treatment against baseline levels and placebo using multiplicity correction.ResultsAt both primary and study endpoints for both populations, higher doses of retatrutide were associated with changes in a cluster of metabolites comprising 3-hydroxybutyrate, acetylcarnitine, free carnitine, and fatty acid-derived long-chain acylcarnitines. Mediation analyses suggested that changes in these biomarkers mediated 23.2% of the weight reduction response in participants without T2D and that this mediation was blunted to 12.7% in participants with T2D. Retatrutide treatment was also associated with changes in metabolites associated with insulin resistance, including branched-chain amino acids and their catabolic products, 2-aminoadipic acid, 2-hydroxybutyrate, urate, and triglycerides enriched in short-chain and saturated acyl side chains. These changes were found in both study populations and sustained across study endpoints.ConclusionRetatrutide was associated with changes in 2 metabolic clusters related to fatty acid oxidation and insulin resistance in a direction associated with improved metabolic health and reduced cardiovascular risk.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. 4 results from people.

  1. 01HumanRandomized controlled trialMechanism

    In adults with obesity without type 2 diabetes, changes in these biomarkers mediated 23.2% of the weight-reduction response to retatrutide.

    In plain wordsIn adults with obesity without type 2 diabetes, changes in these blood markers explained part of the weight loss with retatrutide.

    Peptide
    Retatrutide
    Outcome
    Not applicableMediation of weight reduction by metabolite cluster, participants without T2D
    Study

    n = 282

    Analysis
    Exploratory
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    1, 4, 8, 12 mg · 36 weeksAs given in this study (human).

    Measurements

    Mediated share of weight reduction
    23.2%
    without T2D

    Source sentences

    Summary
    Mediation analyses suggested that changes in these biomarkers mediated 23.2% of the weight reduction response in participants without T2D and that this mediation was blunted to 12.7% in participants with T2D.
    1 context sentence
    Summary · context
    Metabolomics and lipidomics were performed in fasting samples from 2 randomized, placebo-controlled phase 2 trials as a post hoc exploratory analysis.
  2. 02HumanRandomized controlled trialMechanism

    In adults with obesity and type 2 diabetes, the share of the retatrutide weight-reduction response mediated by these biomarkers was blunted to 12.7%.

    In plain wordsIn adults with obesity and type 2 diabetes, these blood markers explained a smaller part of the weight loss with retatrutide.

    Peptide
    Retatrutide
    Outcome
    Not applicableMediation of weight reduction by metabolite cluster, participants with T2D
    Study

    n = 213

    Analysis
    Exploratory
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    0.5-12 mg · 48 weeksAs given in this study (human).

    Measurements

    Mediated share of weight reduction
    12.7%
    with T2D

    Source sentences

    Summary
    Mediation analyses suggested that changes in these biomarkers mediated 23.2% of the weight reduction response in participants without T2D and that this mediation was blunted to 12.7% in participants with T2D.
    1 context sentence
    Summary · context
    Metabolomics and lipidomics were performed in fasting samples from 2 randomized, placebo-controlled phase 2 trials as a post hoc exploratory analysis.
  3. 03HumanRandomized controlled trialMechanism

    In adults with obesity with or without type 2 diabetes, higher retatrutide doses were associated with changes in a cluster of metabolites including 3-hydroxybutyrate, acetylcarnitine, free carnitine and acylcarnitines.

    In plain wordsIn adults with obesity, with or without type 2 diabetes, higher retatrutide doses were linked to changes in fat-burning related blood molecules.

    Peptide
    Retatrutide
    Outcome
    Direction not reportedFatty acid oxidation metabolite cluster
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Exploratory
    Outcome group
    Metabolic pathways and metabolomics · Metabolic and weight
    Studied dose
    higher doses (up to 12 mg) · 36 weeks (obesity trial); 48 weeks (T2D trial)As given in this study (human).

    Source sentences

    Summary
    At both primary and study endpoints for both populations, higher doses of retatrutide were associated with changes in a cluster of metabolites comprising 3-hydroxybutyrate, acetylcarnitine, free carnitine, and fatty acid-derived long-chain acylcarnitines.
    1 context sentence
    Summary · context
    Metabolomics and lipidomics were performed in fasting samples from 2 randomized, placebo-controlled phase 2 trials as a post hoc exploratory analysis.
  4. 04HumanRandomized controlled trialMechanism

    In adults with obesity with or without type 2 diabetes, retatrutide was associated with changes in metabolites linked to insulin resistance, including branched-chain amino acids, 2-aminoadipic acid, 2-hydroxybutyrate, urate and triglycerides.

    In plain wordsIn adults with obesity, with or without type 2 diabetes, retatrutide was linked to changes in blood molecules tied to insulin resistance.

    Peptide
    Retatrutide
    Outcome
    Direction not reportedInsulin resistance-related metabolites
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Exploratory
    Outcome group
    Metabolic pathways and metabolomics · Metabolic and weight
    Studied dose
    higher doses (up to 12 mg) · 36 weeks (obesity trial); 48 weeks (T2D trial)As given in this study (human).

    Source sentences

    Summary
    Retatrutide treatment was also associated with changes in metabolites associated with insulin resistance, including branched-chain amino acids and their catabolic products, 2-aminoadipic acid, 2-hydroxybutyrate, urate, and triglycerides enriched in short-chain and saturated acyl side chains.
    2 context sentences
    Summary · context
    These changes were found in both study populations and sustained across study endpoints.
    Summary · context
    Metabolomics and lipidomics were performed in fasting samples from 2 randomized, placebo-controlled phase 2 trials as a post hoc exploratory analysis.

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.

  1. Versions 4 to 8Current

    28 Oct 2026, 02:03 UTC

    The same notice was added 5 times, first on 22 Oct 2026, 02:26 UTC. The status did not change between them.

    Study results updated

  2. Version 3

    21 Oct 2026, 18:59 UTC

    Study data updated · source update from Europe PMC

  3. Version 2

    9 Oct 2026, 18:17 UTC

    Study results updated

  4. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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