LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial.

Urva S, Coskun T, Loh MT, Du Y, Thomas MK, Gurbuz S, Haupt A, Benson CT, Hernandez-Illas M, D'Alessio DA, Milicevic Z

Lancet (London, England)27 Oct 2022Cited by 150 (Europe PMC)

PMID36354040DOI10.1016/s0140-6736(22)02033-5PepBankPUB-36354040

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: Publisher copyright. Results still quote short attributed sentences.

Results from this study13

13 results from studies that gave the peptide. 13 results from people.

01HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, treatment-emergent adverse events were reported by 63% of participants given LY3437943, 60% given dulaglutide 1.5 mg and 54% given placebo.
In plain wordsIn adults with type 2 diabetes, 63% of people given retatrutide reported side effects, compared with 54% on placebo and 60% on dulaglutide.
Peptide
Retatrutide
Outcome
Not applicableTreatment-emergent adverse events
Study
n = 72
Comparator
Placebo and dulaglutide 1.5 mg
Analysis
Primary
Outcome group
Adverse events · Whole body
Studied dose
0.5 mg, 1.5 mg, 3 mg, 3/6 mg and 3/6/9/12 mg once weekly · subcutaneous · 12 weeksAs given in this study (human).
Measurements
Treatment-emergent adverse events
63%
LY3437943
Treatment-emergent adverse events
60%
dulaglutide 1.5 mg
Treatment-emergent adverse events
54%
placebo
Source sentences
Summary
Treatment-emergent adverse events were reported by 33 (63%), three (60%), and eight (54%) participants who received LY3437943, dulaglutide 1·5 mg, and placebo, respectively, with gastrointestinal disorders being the most frequently reported treatment-emergent adverse events.
3 context sentences(design, population, supporting numbers)
Summary · context
15 participants had placebo, five had dulaglutide 1·5 mg and, for LY3437943, nine had 0·5 mg, nine had 1·5 mg, 11 had 3 mg, 11 had 3/6 mg, and 12 had 3/6/9/12 mg.
Summary · context
We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.
Summary · context
Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period.
Report a problemFND-3635404001
02HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, gastrointestinal disorders were the most frequently reported treatment-emergent adverse events.
In plain wordsIn adults with type 2 diabetes, stomach and gut problems were the side effects reported most often.
Peptide
Retatrutide
Outcome
Not applicableGastrointestinal disorders as most frequent adverse events
Study
n = 72
Analysis
Primary
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
0.5 mg, 1.5 mg, 3 mg, 3/6 mg and 3/6/9/12 mg once weekly · subcutaneous · 12 weeksAs given in this study (human).
Source sentences
Summary
with gastrointestinal disorders being the most frequently reported treatment-emergent adverse events.
3 context sentences(design, population, supporting numbers)
Summary · context
15 participants had placebo, five had dulaglutide 1·5 mg and, for LY3437943, nine had 0·5 mg, nine had 1·5 mg, 11 had 3 mg, 11 had 3/6 mg, and 12 had 3/6/9/12 mg.
Summary · context
We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.
Summary · context
Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period.
Report a problemFND-3635404002
03HumanRandomized controlled trialPharmacokinetics
In adults with type 2 diabetes, the pharmacokinetics of LY3437943 were dose proportional.
In plain wordsIn adults with type 2 diabetes, blood levels of retatrutide rose in proportion to the dose.
Peptide
Retatrutide
Outcome
Not applicableDose proportionality of pharmacokinetics
Study
n: not reported in source
Analysis
Secondary
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
0.5 mg, 1.5 mg, 3 mg, 3/6 mg and 3/6/9/12 mg once weekly · subcutaneous · 12 weeksAs given in this study (human).
Source sentences
Summary
The pharmacokinetics of LY3437943 were dose proportional
3 context sentences(design, population, supporting numbers)
Summary · context
15 participants had placebo, five had dulaglutide 1·5 mg and, for LY3437943, nine had 0·5 mg, nine had 1·5 mg, 11 had 3 mg, 11 had 3/6 mg, and 12 had 3/6/9/12 mg.
Summary · context
We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.
Summary · context
Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period.
Report a problemFND-3635404004
04HumanRandomized controlled trialPharmacokinetics
In adults with type 2 diabetes, the half-life of LY3437943 was approximately 6 days.
In plain wordsIn adults with type 2 diabetes, retatrutide stayed in the body with a half-life of about 6 days.
Peptide
Retatrutide
Outcome
Not applicableHalf-life
Study
n: not reported in source
Analysis
Secondary
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
0.5 mg, 1.5 mg, 3 mg, 3/6 mg and 3/6/9/12 mg once weekly · subcutaneous · 12 weeksAs given in this study (human).
Measurements
Half-life
≈ 6 days
LY3437943
Source sentences
Summary
its half-life was approximately 6 days.
2 context sentences(design, population, supporting numbers)
Summary · context
We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.
Summary · context
Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period.
Report a problemFND-3635404005
05HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, LY3437943 3 mg lowered placebo-adjusted mean daily plasma glucose at week 12 by 2.8 mmol/L.
In plain wordsIn adults with type 2 diabetes, retatrutide 3 mg lowered daily blood glucose more than placebo after 12 weeks.
Peptide
Retatrutide
Outcome
DecreaseMean daily plasma glucose at week 12, 3 mg
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
3 mg once weekly · subcutaneous · 12 weeksAs given in this study (human).
Measurements
Placebo-adjusted mean daily plasma glucose difference
−2.8 mmol/L
3 mg
Source sentences
Summary
least-squares mean difference -2·8 mmol/L [90% CI -4·63 to -0·94] for 3 mg
3 context sentences(design, population, supporting numbers)
Summary · context
At week 12, placebo-adjusted mean daily plasma glucose significantly decreased from baseline at the three highest dose LY3437943 groups
Summary · context
We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.
Summary · context
Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period.
Report a problemFND-3635404006
06HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, LY3437943 3/6 mg lowered placebo-adjusted mean daily plasma glucose at week 12 by 3.1 mmol/L.
In plain wordsIn adults with type 2 diabetes, retatrutide 3/6 mg lowered daily blood glucose more than placebo after 12 weeks.
Peptide
Retatrutide
Outcome
DecreaseMean daily plasma glucose at week 12, 3/6 mg
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
3/6 mg once weekly · subcutaneous · 12 weeksAs given in this study (human).
Measurements
Placebo-adjusted mean daily plasma glucose difference
−3.1 mmol/L
3/6 mg
Source sentences
Summary
-3·1 mmol/L [-4·91 to -1·22] for 3/6 mg
3 context sentences(design, population, supporting numbers)
Summary · context
At week 12, placebo-adjusted mean daily plasma glucose significantly decreased from baseline at the three highest dose LY3437943 groups
Summary · context
We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.
Summary · context
Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period.
Report a problemFND-3635404007
07HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, LY3437943 3/6/9/12 mg lowered placebo-adjusted mean daily plasma glucose at week 12 by 2.9 mmol/L.
In plain wordsIn adults with type 2 diabetes, retatrutide 3/6/9/12 mg lowered daily blood glucose more than placebo after 12 weeks.
Peptide
Retatrutide
Outcome
DecreaseMean daily plasma glucose at week 12, 3/6/9/12 mg
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
3/6/9/12 mg once weekly · subcutaneous · 12 weeksAs given in this study (human).
Measurements
Placebo-adjusted mean daily plasma glucose difference
−2.9 mmol/L
3/6/9/12 mg
Source sentences
Summary
-2·9 mmol/L [-4·70 to -1·01] for 3/6/9/12 mg)
3 context sentences(design, population, supporting numbers)
Summary · context
At week 12, placebo-adjusted mean daily plasma glucose significantly decreased from baseline at the three highest dose LY3437943 groups
Summary · context
We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.
Summary · context
Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period.
Report a problemFND-3635404008
08HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, LY3437943 3 mg lowered placebo-adjusted HbA1c by 1.4%.
In plain wordsIn adults with type 2 diabetes, retatrutide 3 mg lowered long-term blood sugar (HbA1c) more than placebo.
Peptide
Retatrutide
Outcome
DecreaseHbA1c change, 3 mg
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
3 mg once weekly · subcutaneous · 12 weeksAs given in this study (human).
Measurements
Placebo-adjusted HbA1c change
−1.4%
3 mg
Source sentences
Summary
-1·4% [90% CI -2·17 to -0·56] for 3 mg
3 context sentences(design, population, supporting numbers)
Summary · context
Placebo-adjusted sHbA_1c also decreased significantly in the three highest dose groups
Summary · context
We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.
Summary · context
Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period.
Report a problemFND-3635404009
09HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, LY3437943 3/6 mg lowered placebo-adjusted HbA1c by 1.6%.
In plain wordsIn adults with type 2 diabetes, retatrutide 3/6 mg lowered long-term blood sugar (HbA1c) more than placebo.
Peptide
Retatrutide
Outcome
DecreaseHbA1c change, 3/6 mg
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
3/6 mg once weekly · subcutaneous · 12 weeksAs given in this study (human).
Measurements
Placebo-adjusted HbA1c change
−1.6%
3/6 mg
Source sentences
Summary
-1·6% [-2·37 to -0·75] for 3/6 mg
3 context sentences(design, population, supporting numbers)
Summary · context
Placebo-adjusted sHbA_1c also decreased significantly in the three highest dose groups
Summary · context
We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.
Summary · context
Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period.
Report a problemFND-3635404010
10HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, LY3437943 3/6/9/12 mg lowered placebo-adjusted HbA1c by 1.2%.
In plain wordsIn adults with type 2 diabetes, retatrutide 3/6/9/12 mg lowered long-term blood sugar (HbA1c) more than placebo.
Peptide
Retatrutide
Outcome
DecreaseHbA1c change, 3/6/9/12 mg
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
3/6/9/12 mg once weekly · subcutaneous · 12 weeksAs given in this study (human).
Measurements
Placebo-adjusted HbA1c change
−1.2%
3/6/9/12 mg
Source sentences
Summary
-1·2% [-2·05 to -0·45] for 3/6/9/12 mg)
3 context sentences(design, population, supporting numbers)
Summary · context
Placebo-adjusted sHbA_1c also decreased significantly in the three highest dose groups
Summary · context
We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.
Summary · context
Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period.
Report a problemFND-3635404011
11HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, LY3437943 reduced placebo-adjusted bodyweight in a dose-dependent way, by up to 8.96 kg in the 3/6/9/12 mg group.
In plain wordsIn adults with type 2 diabetes, retatrutide cut body weight more than placebo, and higher doses cut more.
Peptide
Retatrutide
Outcome
DecreaseBodyweight change
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
dose dependent, up to 3/6/9/12 mg once weekly · subcutaneous · 12 weeksAs given in this study (human).
Measurements
Placebo-adjusted bodyweight change
−8.96 kg
3/6/9/12 mg
Source sentences
Summary
Placebo-adjusted bodyweight reduction with LY3437943 appeared to be dose dependent (up to -8·96 kg [90% CI -11·16 to -6·75] in the 3/6/9/12 mg group).
2 context sentences(design, population, supporting numbers)
Summary · context
We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.
Summary · context
Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period.
Report a problemFND-3635404012
12HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, 29 participants discontinued the study early; the abstract does not split this number by treatment arm.
In plain wordsIn adults with type 2 diabetes, 29 people left the study early. The abstract does not say how many were in each group.
Peptide
Retatrutide
Outcome
Not applicablePremature study discontinuation
Study
n = 72
Outcome group
Adverse events · Whole body
Studied dose
0.5 mg, 1.5 mg, 3 mg, 3/6 mg and 3/6/9/12 mg once weekly · subcutaneous · 12 weeksAs given in this study (human).
Measurements
Participants who discontinued
29 participants
all arms
Source sentences
Summary
29 participants discontinued the study prematurely.
2 context sentences(design, population, supporting numbers)
Summary · context
We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.
Summary · context
Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period.
Report a problemFND-3635404003
13HumanRandomized controlled trialSafety outcome
In people with type 2 diabetes, three dulaglutide recipients reported treatment-emergent adverse events, representing 60% of that arm.
In plain wordsIn people with diabetes, 60% of dulaglutide recipients reported treatment-emergent adverse events.
Peptide
Dulaglutide (Trulicity)
Outcome
Not applicableTreatment-emergent adverse events
Study
n = 5
Outcome group
Adverse events · Whole body
Studied dose
1.5 mg once weekly · subcutaneous · 12 weeksAs given in this study (human).
Measurements
Treatment-emergent adverse events
60%
dulaglutide
Participants with treatment-emergent adverse events
3 participants
dulaglutide
Source sentences
Summary
Treatment-emergent adverse events were reported by 33 (63%), three (60%), and eight (54%) participants who received LY3437943, dulaglutide 1·5 mg, and placebo, respectively, with gastrointestinal disorders being the most frequently reported treatment-emergent adverse events.
2 context sentences(design, population, supporting numbers)
Summary · context
Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period.
Summary · context
15 participants had placebo, five had dulaglutide 1·5 mg and, for LY3437943, nine had 0·5 mg, nine had 1·5 mg, 11 had 3 mg, 11 had 3/6 mg, and 12 had 3/6/9/12 mg.
Report a problemFND-3635404013

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 · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 1NCT04143802

A Study of LY3437943 in Participants With Type 2 Diabetes Mellitus (T2DM)

Eli Lilly and Companyn = 7218 Dec 2019 to 28 Dec 2020

Diabetes Mellitus, Type 2

Trial page ClinicalTrials.govUpdated 20 Jan 2021

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
9 Oct 2026, 19:08 UTC
Study results updated
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC