Effects of Tirzepatide, a Dual GIP and GLP-1 RA, on Lipid and Metabolite Profiles in Subjects With Type 2 Diabetes.

Pirro V, Roth KD, Lin Y, Willency JA, Milligan PL, Wilson JM, Ruotolo G, Haupt A, Newgard CB, Duffin KL

The Journal of clinical endocrinology and metabolism1 Jan 2022Cited by 95 (Europe PMC)

PMID34608929DOI10.1210/clinem/dgab722PepBankPUB-34608929

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: Publisher copyright. Results still quote short attributed sentences.

Results from this study11

11 results from studies that gave the peptide. 11 results from people.

01HumanRandomized controlled trialMechanism
In adults with type 2 diabetes, higher-dose tirzepatide modulated a cluster of metabolites and lipids associated with insulin resistance, obesity and future type 2 diabetes risk at 26 weeks.
In plain wordsIn adults with type 2 diabetes, higher-dose tirzepatide changed a group of blood metabolites linked to insulin resistance and obesity.
Peptide
Tirzepatide
Outcome
MixedCluster of metabolites and lipids linked to insulin resistance
Study
n = 259
Analysis
Exploratory
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
higher dose · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
At 26 weeks, a higher dose tirzepatide modulated a cluster of metabolites and lipids associated with IR, obesity, and future T2D risk.
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks.
Summary · context
259 subjects with T2D.
Report a problemFND-3460892901
02HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, branched-chain amino acids decreased with higher-dose tirzepatide compared with baseline and placebo.
In plain wordsIn adults with type 2 diabetes, higher-dose tirzepatide lowered branched-chain amino acids compared with baseline and placebo.
Peptide
Tirzepatide
Outcome
DecreaseBranched-chain amino acids
Study
n = 259
Comparator
Baseline and placebo
Analysis
Exploratory
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
higher dose · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
Branched-chain amino acids, direct catabolic products glutamate, 3-hydroxyisobutyrate, branched-chain ketoacids, and indirect byproducts such as 2-hydroxybutyrate decreased compared to baseline and placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks.
Summary · context
259 subjects with T2D.
Report a problemFND-3460892902
03HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, glutamate, 3-hydroxyisobutyrate and branched-chain ketoacids decreased with higher-dose tirzepatide compared with baseline and placebo.
In plain wordsIn adults with type 2 diabetes, higher-dose tirzepatide lowered breakdown products of branched-chain amino acids compared with baseline and placebo.
Peptide
Tirzepatide
Outcome
DecreaseDirect catabolic products of branched-chain amino acids
Study
n = 259
Comparator
Baseline and placebo
Analysis
Exploratory
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
higher dose · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
Branched-chain amino acids, direct catabolic products glutamate, 3-hydroxyisobutyrate, branched-chain ketoacids, and indirect byproducts such as 2-hydroxybutyrate decreased compared to baseline and placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks.
Summary · context
259 subjects with T2D.
Report a problemFND-3460892903
04HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, indirect byproducts such as 2-hydroxybutyrate decreased with higher-dose tirzepatide compared with baseline and placebo.
In plain wordsIn adults with type 2 diabetes, higher-dose tirzepatide lowered 2-hydroxybutyrate and similar byproducts compared with baseline and placebo.
Peptide
Tirzepatide
Outcome
DecreaseIndirect byproducts such as 2-hydroxybutyrate
Study
n = 259
Comparator
Baseline and placebo
Analysis
Exploratory
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
higher dose · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
Branched-chain amino acids, direct catabolic products glutamate, 3-hydroxyisobutyrate, branched-chain ketoacids, and indirect byproducts such as 2-hydroxybutyrate decreased compared to baseline and placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks.
Summary · context
259 subjects with T2D.
Report a problemFND-3460892904
05HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, changes in these metabolites were significantly larger with tirzepatide than with dulaglutide.
In plain wordsIn adults with type 2 diabetes, tirzepatide changed these blood metabolites more than dulaglutide.
Peptide
Tirzepatide
Outcome
DecreaseMetabolite changes vs dulaglutide
Study
n = 259
Comparator
Dulaglutide
Analysis
Exploratory
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
higher dose · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
Changes were significantly larger with tirzepatide compared with dulaglutide and directly proportional to reductions of HbA1c, homeostatic model assessment 2-IR indices, and proinsulin levels.
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks.
Summary · context
259 subjects with T2D.
Report a problemFND-3460892905
06HumanRandomized controlled trialMechanism
In adults with type 2 diabetes, metabolite changes with tirzepatide were directly proportional to reductions of HbA1c, HOMA2-IR indices and proinsulin levels.
In plain wordsIn adults with type 2 diabetes on tirzepatide, larger metabolite changes went with larger drops in HbA1c, insulin resistance and proinsulin.
Peptide
Tirzepatide
Outcome
Not applicableMetabolite changes in proportion to HbA1c, HOMA2-IR and proinsulin reductions
Study
n = 259
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
higher dose · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
directly proportional to reductions of HbA1c, homeostatic model assessment 2-IR indices, and proinsulin levels.
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks.
Summary · context
259 subjects with T2D.
Report a problemFND-3460892906
07HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, triglycerides were lowered significantly with tirzepatide compared with baseline, dulaglutide and placebo, with a bias toward shorter and highly saturated species.
In plain wordsIn adults with type 2 diabetes, tirzepatide lowered triglycerides compared with baseline, dulaglutide and placebo.
Peptide
Tirzepatide
Outcome
DecreaseTriglycerides
Study
n = 259
Comparator
Baseline, dulaglutide and placebo
Analysis
Exploratory
Outcome group
Lipids · Metabolic and weight
Studied dose
higher dose · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
Proportional to metabolite changes, triglycerides and diglycerides were lowered significantly compared to baseline, dulaglutide, and placebo, with a bias toward shorter and highly saturated species.
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks.
Summary · context
259 subjects with T2D.
Report a problemFND-3460892907
08HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, diglycerides were lowered significantly with tirzepatide compared with baseline, dulaglutide and placebo, with a bias toward shorter and highly saturated species.
In plain wordsIn adults with type 2 diabetes, tirzepatide lowered diglycerides compared with baseline, dulaglutide and placebo.
Peptide
Tirzepatide
Outcome
DecreaseDiglycerides
Study
n = 259
Comparator
Baseline, dulaglutide and placebo
Analysis
Exploratory
Outcome group
Lipids · Metabolic and weight
Studied dose
higher dose · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
Proportional to metabolite changes, triglycerides and diglycerides were lowered significantly compared to baseline, dulaglutide, and placebo, with a bias toward shorter and highly saturated species.
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks.
Summary · context
259 subjects with T2D.
Report a problemFND-3460892908
09HumanRandomized controlled trialEfficacy outcome
In patients with type 2 diabetes, changes in branched-chain amino acids and related metabolites at 26 weeks were significantly larger with higher-dose tirzepatide than with dulaglutide.
In plain wordsIn patients with diabetes, changes in these blood metabolites were larger with higher-dose tirzepatide than with dulaglutide.
Peptide
Dulaglutide (Trulicity)
Outcome
Direction not reportedMetabolite changes
Study
n: not reported in source
Comparator
Tirzepatide
Analysis
Exploratory
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
1.5 mg weekly · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
Changes were significantly larger with tirzepatide compared with dulaglutide and directly proportional to reductions of HbA1c, homeostatic model assessment 2-IR indices, and proinsulin levels.
1 context sentence(design, population, supporting numbers)
Summary · context
Branched-chain amino acids, direct catabolic products glutamate, 3-hydroxyisobutyrate, branched-chain ketoacids, and indirect byproducts such as 2-hydroxybutyrate decreased compared to baseline and placebo.
Report a problemFND-3460892909
10HumanRandomized controlled trialEfficacy outcome
In patients with type 2 diabetes, triglycerides at 26 weeks were higher with dulaglutide than with higher-dose tirzepatide.
In plain wordsIn patients with diabetes, triglycerides were higher with dulaglutide than with higher-dose tirzepatide.
Peptide
Dulaglutide (Trulicity)
Outcome
IncreaseTriglycerides
Study
n: not reported in source
Comparator
Tirzepatide
Analysis
Exploratory
Outcome group
Lipids · Metabolic and weight
Studied dose
1.5 mg weekly · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
Proportional to metabolite changes, triglycerides and diglycerides were lowered significantly compared to baseline, dulaglutide, and placebo, with a bias toward shorter and highly saturated species.
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks.
Summary · context
Tirzepatide (1, 5, 10, 15 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-3460892910
11HumanRandomized controlled trialEfficacy outcome
In patients with type 2 diabetes, diglycerides at 26 weeks were higher with dulaglutide than with higher-dose tirzepatide.
In plain wordsIn patients with diabetes, diglycerides were higher with dulaglutide than with higher-dose tirzepatide.
Peptide
Dulaglutide (Trulicity)
Outcome
IncreaseDiglycerides
Study
n: not reported in source
Comparator
Tirzepatide
Analysis
Exploratory
Outcome group
Lipids · Metabolic and weight
Studied dose
1.5 mg weekly · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
Proportional to metabolite changes, triglycerides and diglycerides were lowered significantly compared to baseline, dulaglutide, and placebo, with a bias toward shorter and highly saturated species.
2 context sentences(design, population, supporting numbers)
Summary · context
Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks.
Summary · context
Tirzepatide (1, 5, 10, 15 mg), dulaglutide (1.5 mg), or placebo.
Report a problemFND-3460892911

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 2Results postedNCT03131687

A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Mellitus

Eli Lilly and Companyn = 31824 May 2017 to 1 Aug 2018

Type 2 Diabetes Mellitus

Trial page ClinicalTrials.govUpdated 20 Aug 2019

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.

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
Version 3
21 Oct 2026, 18:59 UTC
Study data updated · source update from Europe PMC
Version 2
12 Oct 2026, 12:58 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC