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Study · Randomized controlled trial · 2018

10 results

LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept.

Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS and 4 more

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Benson CT, Gimeno RE, D'Alessio DA, Haupt A

Molecular metabolism3 Oct 2018Cited by 700 (Europe PMC)

PMID30473097 (opens in a new tab)PMCIDPMC6308032 (opens in a new tab)DOI10.1016/j.molmet.2018.09.009 (opens in a new tab)PepBankPUB-30473097
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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: CC BY-NC-ND. Results still quote short attributed sentences.

Results from this study10

10 results from studies that gave the peptide. 5 results from people.

  1. 01HumanRandomized controlled trialSafety outcome

    In healthy subjects and patients with type 2 diabetes, the most frequent side effects of LY3298176 (tirzepatide) were gastrointestinal (vomiting, nausea, decreased appetite, diarrhoea, abdominal distension), dose-dependent and mild to moderate.

    In plain wordsIn early human trials, the most common side effects of tirzepatide were stomach and gut problems, which grew with dose and were mild to moderate.

    Peptide
    Tirzepatide
    Outcome
    Not applicableAdverse events (mostly gastrointestinal, dose-dependent)
    Study

    n: not reported in source

    Analysis
    Primary
    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    0.25-15 mg across the single-dose, multiple-dose and proof-of-concept parts · subcutaneous · single dose (SAD) and 4 weeks (MAD and POC)As given in this study (human).

    Source sentences

    Summary
    The most frequent side effects reported with LY3298176 were gastrointestinal (vomiting, nausea, decreased appetite, diarrhoea, and abdominal distension) in both HS and patients with T2DM; all were dose-dependent and considered mild to moderate in severity.
    2 context sentences
    Summary · context
    A Phase 1, randomised, placebo-controlled, double-blind study was comprised of three parts: a single-ascending dose (SAD; doses 0.25-8 mg) and 4-week multiple-ascending dose (MAD; doses 0.5-10 mg) studies in healthy subjects (HS), followed by a 4-week multiple-dose Phase 1 b proof-of-concept (POC; d…
    Summary · context
    The primary objective was to investigate safety and tolerability of LY3298176.
  2. 02HumanRandomized controlled trialPharmacokinetics

    In the phase 1 programme in healthy subjects and patients with type 2 diabetes, the pharmacokinetic profile of LY3298176 (tirzepatide) over 0.25-15 mg supported once-weekly administration.

    In plain wordsIn early human trials, the way the body handled tirzepatide supported dosing once a week.

    Peptide
    Tirzepatide
    Outcome
    Not applicablePharmacokinetic profile across 0.25-15 mg
    Study

    n: not reported in source

    Outcome group
    Pharmacokinetics · Pharmacology
    Studied dose
    0.25-15 mg · subcutaneousAs given in this study (human).

    Source sentences

    Summary
    The PK profile of LY3298176 was investigated over a wide dose range (0.25-15 mg) and supports once-weekly administration.
    2 context sentences
    Summary · context
    A Phase 1, randomised, placebo-controlled, double-blind study was comprised of three parts: a single-ascending dose (SAD; doses 0.25-8 mg) and 4-week multiple-ascending dose (MAD; doses 0.5-10 mg) studies in healthy subjects (HS), followed by a 4-week multiple-dose Phase 1 b proof-of-concept (POC; d…
    Summary · context
    A total of 142 human subjects received at least 1 dose of LY3298176, dulaglutide, or placebo.
  3. 03HumanRandomized controlled trialEfficacy outcome

    In patients with type 2 diabetes in the 4-week phase 1b trial, LY3298176 (tirzepatide) 10 mg and 15 mg significantly reduced fasting serum glucose versus placebo (least square mean differences -49.12 and -43.15 mg/dL).

    In plain wordsIn a short early trial in people with type 2 diabetes, tirzepatide 10 mg and 15 mg lowered fasting blood sugar more than placebo.

    Peptide
    Tirzepatide
    Outcome
    DecreaseFasting serum glucose in patients with type 2 diabetes
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    10 mg and 15 mg (doses above 5 mg reached by titration) · subcutaneous · 4 weeksAs given in this study (human).

    Measurements

    Fasting serum glucose difference vs placebo (reduction)
    49.12 mg/dL
    LY3298176 10 mg
    Fasting serum glucose difference vs placebo (reduction)
    43.15 mg/dL
    LY3298176 15 mg

    Source sentences

    Summary
    In the Phase 1 b trial of diabetic subjects, LY3298176 doses of 10 mg and 15 mg significantly reduced fasting serum glucose compared to placebo (least square mean [LSM] difference [95% CI]: -49.12 mg/dL [-78.14, -20.12] and -43.15 mg/dL [-73.06, -13.21], respectively).
    2 context sentences
    Summary · context
    followed by a 4-week multiple-dose Phase 1 b proof-of-concept (POC; doses 0.5-15 mg) in patients with T2DM
    Summary · context
    Doses higher than 5 mg were attained by titration
  4. 04HumanRandomized controlled trialEfficacy outcome

    In healthy subjects in the 4-week multiple-ascending dose study, LY3298176 (tirzepatide) 1.5, 4.5 and 10 mg reduced body weight significantly more than placebo (least square mean differences -1.75, -5.09 and -4.61 kg).

    In plain wordsIn a short early trial in healthy volunteers, body weight fell more with tirzepatide than with placebo.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody weight in healthy subjects (multiple-ascending dose)
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    1.5 mg, 4.5 mg or 10 mg · subcutaneous · 4 weeksAs given in this study (human).

    Measurements

    Body weight difference vs placebo (reduction)
    1.75 kg
    LY3298176 1.5 mg, healthy subjects
    Body weight difference vs placebo (reduction)
    5.09 kg
    LY3298176 4.5 mg, healthy subjects
    Body weight difference vs placebo (reduction)
    4.61 kg
    LY3298176 10 mg, healthy subjects

    Source sentences

    Summary
    Reductions in body weight were significantly greater with the LY3298176 1.5 mg, 4.5 mg and 10 mg doses versus placebo in MAD HS (LSM difference [95% CI]: -1.75 kg [-3.38, -0.12], -5.09 kg [-6.72, -3.46] and -4.61 kg [-6.21, -3.01], respectively)
    2 context sentences
    Summary · context
    A Phase 1, randomised, placebo-controlled, double-blind study was comprised of three parts: a single-ascending dose (SAD; doses 0.25-8 mg) and 4-week multiple-ascending dose (MAD; doses 0.5-10 mg) studies in healthy subjects (HS), followed by a 4-week multiple-dose Phase 1 b proof-of-concept (POC; d…
    Summary · context
    4-week multiple-ascending dose (MAD; doses 0.5-10 mg) studies in healthy subjects (HS)
  5. 05HumanRandomized controlled trialEfficacy outcome

    In patients with type 2 diabetes in the 4-week phase 1b trial, LY3298176 (tirzepatide) 10 mg and 15 mg had a relevant effect on body weight (least square mean differences -2.62 and -2.07 kg).

    In plain wordsIn a short early trial in people with type 2 diabetes, body weight fell with tirzepatide 10 mg and 15 mg.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody weight in patients with type 2 diabetes (proof-of-concept study)
    Study

    n: not reported in source

    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    10 mg and 15 mg (doses above 5 mg reached by titration) · subcutaneous · 4 weeksAs given in this study (human).

    Measurements

    Body weight difference (reduction)
    2.62 kg
    LY3298176 10 mg, patients with T2DM
    Body weight difference (reduction)
    2.07 kg
    LY3298176 15 mg, patients with T2DM

    Source sentences

    Summary
    and doses of 10 mg and 15 mg had a relevant effect in T2DM patients (LSM difference [95% CI]: -2.62 kg [-3.79, -1.45] and -2.07 kg [-3.25, -0.88], respectively.
    2 context sentences
    Summary · context
    A Phase 1, randomised, placebo-controlled, double-blind study was comprised of three parts: a single-ascending dose (SAD; doses 0.25-8 mg) and 4-week multiple-ascending dose (MAD; doses 0.5-10 mg) studies in healthy subjects (HS), followed by a 4-week multiple-dose Phase 1 b proof-of-concept (POC; d…
    Summary · context
    followed by a 4-week multiple-dose Phase 1 b proof-of-concept (POC; doses 0.5-15 mg) in patients with T2DM
  6. 06AnimalAnimal study (in vivo)Efficacy outcome

    In mice, LY3298176 (tirzepatide) produced glucose-dependent insulin secretion by acting on both GIP and GLP-1 receptors.

    In plain wordsIn mice, tirzepatide triggered insulin release that depended on blood glucose, acting on both GIP and GLP-1 receptors.

    Peptide
    Tirzepatide
    Outcome
    IncreaseGlucose-dependent insulin secretion
    Study

    micen: not reported in source

    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    showed glucose-dependent insulin secretion and improved glucose tolerance by acting on both GIP and GLP-1 receptors in mice
    1 context sentence
    Summary · context
    and in vivo using body weight, food intake, insulin secretion and glycemic profiles in mice
  7. 07AnimalAnimal study (in vivo)Efficacy outcome

    In mice, LY3298176 (tirzepatide) improved glucose tolerance by acting on both GIP and GLP-1 receptors.

    In plain wordsIn mice, tirzepatide improved how the body handled blood sugar, acting on both GIP and GLP-1 receptors.

    Peptide
    Tirzepatide
    Outcome
    IncreaseGlucose tolerance
    Study

    micen: not reported in source

    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    showed glucose-dependent insulin secretion and improved glucose tolerance by acting on both GIP and GLP-1 receptors in mice
    1 context sentence
    Summary · context
    and in vivo using body weight, food intake, insulin secretion and glycemic profiles in mice
  8. 08AnimalAnimal study (in vivo)Efficacy outcome

    In mice given LY3298176 (tirzepatide) chronically, body weight decreased significantly more than with a GLP-1 receptor agonist.

    In plain wordsIn mice, long-term tirzepatide lowered body weight more than a GLP-1 receptor agonist drug did.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody weight with chronic administration
    Study

    micen: not reported in source

    Comparator
    GLP-1 receptor agonist (not named in the abstract)
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated · chronic administrationAs given in this study (mice).

    Source sentences

    Summary
    With chronic administration to mice, LY3298176 potently decreased body weight and food intake; these effects were significantly greater than the effects of a GLP-1 receptor agonist.
    1 context sentence
    Summary · context
    and in vivo using body weight, food intake, insulin secretion and glycemic profiles in mice
  9. 09AnimalAnimal study (in vivo)Efficacy outcome

    In mice given LY3298176 (tirzepatide) chronically, food intake decreased significantly more than with a GLP-1 receptor agonist.

    In plain wordsIn mice, long-term tirzepatide reduced food intake more than a GLP-1 receptor agonist drug did.

    Peptide
    Tirzepatide
    Outcome
    DecreaseFood intake with chronic administration
    Study

    micen: not reported in source

    Comparator
    GLP-1 receptor agonist (not named in the abstract)
    Outcome group
    Appetite and food intake · Metabolic and weight
    Studied dose
    Dose not stated · chronic administrationAs given in this study (mice).

    Source sentences

    Summary
    With chronic administration to mice, LY3298176 potently decreased body weight and food intake; these effects were significantly greater than the effects of a GLP-1 receptor agonist.
    1 context sentence
    Summary · context
    and in vivo using body weight, food intake, insulin secretion and glycemic profiles in mice
  10. 10LabIn vitro (cells)Activity measurement

    In cell lines expressing recombinant or endogenous incretin receptors, LY3298176 (tirzepatide) activated both GIP and GLP-1 receptor signalling.

    In plain wordsIn cells, tirzepatide switched on both the GIP receptor and the GLP-1 receptor.

    Peptide
    Tirzepatide
    Outcome
    IncreaseGIP and GLP-1 receptor signalling activation
    Study

    n: not reported in source

    Cell lines expressing recombinant or endogenous incretin receptors
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    LY3298176 activated both GIP and GLP-1 receptor signaling in vitro
    1 context sentence
    Summary · context
    LY3298176 was characterised in vitro, using signaling and functional assays in cell lines expressing recombinant or endogenous incretin receptors

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials3

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

3 trials · 2 ongoing · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

RecruitingPhase 2NCT07046819

Tirzepatide in MetALD

National Institute on Alcohol Abuse and Alcoholism (NIAAA)n = 12011 Jun 2026 to est. 30 Jul 2027

Metabolic Alcohol-associated Liver Disease · Alcohol Use Disorder

Trial pageClinicalTrials.govUpdated 12 Aug 2026
RecruitingPhase 4NCT06606821

The Effects of Tirzepatide in People With Overweight/Obesity and Coronary Artery Disease

Tina Vilsbølln = 1241 Oct 2024 to est. 1 Aug 2028

Coronary Artery Disease · Coronary Microvascular Dysfunction · Overweight or Obesity · Stable Angina Pectoris · Chronic Coronary Artery Disease · Atherosclerosis Cardiovascular Disease

Trial pageClinicalTrials.govUpdated 22 May 2025
CompletedPhase 1Results postedNCT02759107

A Study of Tirzepatide (LY3298176) in Healthy Participants and Participants With Type 2 Diabetes (T2DM)

Eli Lilly and Companyn = 14211 May 2016 to 26 Jun 2017

Healthy · Type 2 Diabetes Mellitus (T2DM)

Trial pageClinicalTrials.govUpdated 16 Jan 2024

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, 12:39 UTC

    Study results updated

  4. Version 1

    9 Oct 2026, 03:07 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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