Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial.

Heise T, Mari A, DeVries JH, Urva S, Li J, Pratt EJ, Coskun T, Thomas MK, Mather KJ, Haupt A, Milicevic Z

The lancet. Diabetes & endocrinology22 Apr 2022Cited by 214 (Europe PMC)

PMID35468322DOI10.1016/s2213-8587(22)00085-7PepBankPUB-35468322

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 study12

12 results from studies that gave the peptide. 12 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on metformin, tirzepatide 15 mg once weekly increased the clamp disposition index (a combined measure of insulin secretion and sensitivity) from baseline to week 28 versus placebo (estimated treatment difference 1·92, 95% CI 1·59-2·24).
In plain wordsIn adults with type 2 diabetes, tirzepatide improved a combined measure of insulin release and insulin sensitivity, compared with placebo.
Peptide
Tirzepatide
Outcome
IncreaseClamp disposition index change from baseline to week 28 vs placebo
Study
n = 102
Comparator
Placebo
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
15 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).
Source sentences
Summary
With tirzepatide, the clamp disposition index increased from a least squares mean of 0·3 pmol m^-2 L min^-2 kg^-1 (SE 0·03) at baseline by 1·9 pmol m^-2 L min^-2 kg^-1 (0·16) to total 2·3 pmol m^-2 L min^-2 kg-1</su…
3 context sentences(design, population, supporting numbers)
Summary · context
estimated treatment difference [ETD] tirzepatide vs placebo 1·92 [95% CI 1·59-2·24]; p<0·0001
Summary · context
patients were randomly assigned (3:3:2) to subcutaneously receive either tirzepatide 15 mg, semaglutide 1 mg, or placebo once per week
Summary · context
Because of discontinuations and exclusions due to missing or unevaluable data, 39 patients in each treatment group and 24 patients in the placebo group comprised the pharmacodynamic analysis set.
Report a problemFND-3546832201
02HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, the improvement in clamp disposition index with tirzepatide 15 mg was significantly greater than with semaglutide 1 mg (estimated treatment difference 0·84, 95% CI 0·46-1·21).
In plain wordsIn adults with type 2 diabetes, tirzepatide improved a combined measure of insulin release and insulin sensitivity more than semaglutide.
Peptide
Tirzepatide
Outcome
IncreaseClamp disposition index change vs semaglutide
Study
n = 102
Comparator
Semaglutide 1 mg once weekly
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
15 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).
Source sentences
Summary
The improvement with tirzepatide in clamp disposition index was significantly greater than with semaglutide (ETD 0·84 pmol m^-2 L min^-2 kg^-1 [95% CI 0·46-1·21]).
2 context sentences(design, population, supporting numbers)
Summary · context
patients were randomly assigned (3:3:2) to subcutaneously receive either tirzepatide 15 mg, semaglutide 1 mg, or placebo once per week
Summary · context
Because of discontinuations and exclusions due to missing or unevaluable data, 39 patients in each treatment group and 24 patients in the placebo group comprised the pharmacodynamic analysis set.
Report a problemFND-3546832202
03HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, tirzepatide 15 mg significantly improved total insulin secretion rate versus semaglutide 1 mg (estimated treatment difference 102·09 pmol min-1 m-2, 95% CI 51·84-152·33).
In plain wordsIn adults with type 2 diabetes, tirzepatide increased the body's insulin release more than semaglutide did.
Peptide
Tirzepatide
Outcome
IncreaseTotal insulin secretion rate vs semaglutide
Study
n = 102
Comparator
Semaglutide 1 mg once weekly
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
15 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).
Source sentences
Summary
This result reflected significant improvements in total insulin secretion rate (ETD 102·09 pmol min^-1 m^-2 [51·84-152·33]) and insulin sensitivity (ETD 1·52 mg min^-1 kg^-1 [0·53-2·52]) for tirzepatide versus semaglutide.
2 context sentences(design, population, supporting numbers)
Summary · context
patients were randomly assigned (3:3:2) to subcutaneously receive either tirzepatide 15 mg, semaglutide 1 mg, or placebo once per week
Summary · context
Because of discontinuations and exclusions due to missing or unevaluable data, 39 patients in each treatment group and 24 patients in the placebo group comprised the pharmacodynamic analysis set.
Report a problemFND-3546832203
04HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, tirzepatide 15 mg significantly improved insulin sensitivity versus semaglutide 1 mg (estimated treatment difference 1·52 mg min-1 kg-1, 95% CI 0·53-2·52).
In plain wordsIn adults with type 2 diabetes, tirzepatide improved insulin sensitivity more than semaglutide did.
Peptide
Tirzepatide
Outcome
IncreaseInsulin sensitivity (M value) vs semaglutide
Study
n = 102
Comparator
Semaglutide 1 mg once weekly
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
15 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).
Source sentences
Summary
This result reflected significant improvements in total insulin secretion rate (ETD 102·09 pmol min^-1 m^-2 [51·84-152·33]) and insulin sensitivity (ETD 1·52 mg min^-1 kg^-1 [0·53-2·52]) for tirzepatide versus semaglutide.
2 context sentences(design, population, supporting numbers)
Summary · context
patients were randomly assigned (3:3:2) to subcutaneously receive either tirzepatide 15 mg, semaglutide 1 mg, or placebo once per week
Summary · context
Because of discontinuations and exclusions due to missing or unevaluable data, 39 patients in each treatment group and 24 patients in the placebo group comprised the pharmacodynamic analysis set.
Report a problemFND-3546832204
05HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, tirzepatide 15 mg significantly reduced glucose excursions on a meal tolerance test versus placebo, with a larger effect than semaglutide 1 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide lowered blood sugar rises after a test meal more than placebo, and more than semaglutide did.
Peptide
Tirzepatide
Outcome
DecreaseGlucose excursions on meal tolerance test
Study
n = 102
Comparator
Placebo
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
15 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).
Source sentences
Summary
On meal tolerance testing, tirzepatide significantly reduced glucose excursions (lower insulin and glucagon concentrations) compared with placebo, with effects on these variables being greater than with semaglutide.
2 context sentences(design, population, supporting numbers)
Summary · context
patients were randomly assigned (3:3:2) to subcutaneously receive either tirzepatide 15 mg, semaglutide 1 mg, or placebo once per week
Summary · context
Because of discontinuations and exclusions due to missing or unevaluable data, 39 patients in each treatment group and 24 patients in the placebo group comprised the pharmacodynamic analysis set.
Report a problemFND-3546832205
06HumanRandomized controlled trialSafety outcome
In 117 adults with type 2 diabetes, gastrointestinal events were the most common adverse events; nausea affected 24% on tirzepatide 15 mg versus 25% on placebo, diarrhoea 20% versus 21%, and vomiting 7% versus 4%, and tirzepatide and semaglutide had similar safety profiles.
In plain wordsIn adults with type 2 diabetes, stomach and gut problems were the most common adverse events in the tirzepatide, semaglutide and placebo groups.
Peptide
Tirzepatide
Outcome
Direction not reportedGastrointestinal adverse events (nausea, diarrhoea, vomiting)
Study
n = 117
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
15 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).
Measurements
Nausea incidence
24%
tirzepatide 15 mg
Nausea incidence
25%
placebo
Diarrhoea incidence
20%
tirzepatide 15 mg
Diarrhoea incidence
21%
placebo
Vomiting incidence
7%
tirzepatide 15 mg
Vomiting incidence
4%
placebo
Source sentences
Summary
The safety profiles of tirzepatide and semaglutide were similar, with gastrointestinal adverse events being the most common (11 [24%], 13 [30%], and seven [25%] with nausea; nine [20%], 13 [30%], and six [21%] with diarrhoea; and three [7%], five [11%], and one [4%] with vomiting, for tirzepatide, s…
1 context sentence(design, population, supporting numbers)
Summary · context
Safety was analysed in the safety population, which comprised all randomly assigned participants who received at least one dose of a study drug.
Report a problemFND-3546832207
07HumanRandomized controlled trialSafety outcome
In the 117-participant safety population of a 28-week trial in adults with type 2 diabetes, there were no deaths.
In plain wordsIn this 28-week trial in adults with type 2 diabetes, no one died.
Peptide
Tirzepatide
Outcome
Not applicableDeaths
Study
n = 117
Outcome group
Mortality · Whole body
Studied dose
15 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).
Source sentences
Summary
There were no deaths.
1 context sentence(design, population, supporting numbers)
Summary · context
we screened 184 individuals and enrolled 117 participants, all of whom were included in the safety population
Report a problemFND-3546832208
08HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, no deaths occurred in the trial arms, including the semaglutide 1 mg arm.
In plain wordsIn adults with type 2 diabetes, no deaths occurred in this trial, including in the semaglutide group.
Peptide
Semaglutide
Outcome
Not applicableDeaths
Study
n = 117
Outcome group
Mortality · Whole body
Studied dose
1 mg · subcutaneous · 28 weeksAs given in this study (human).
Source sentences
Summary
There were no deaths.
1 context sentence(design, population, supporting numbers)
Summary · context
Via a randomisation table, patients were randomly assigned (3:3:2) to subcutaneously receive either tirzepatide 15 mg, semaglutide 1 mg, or placebo once per week.
Report a problemFND-3546832212
09HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, tirzepatide 15 mg lowered insulin and glucagon concentrations on a meal tolerance test versus placebo, with larger effects than semaglutide 1 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide lowered insulin and glucagon levels after a test meal compared with placebo, more than semaglutide did.
Peptide
Tirzepatide
Outcome
DecreaseInsulin and glucagon concentrations on meal tolerance test
Study
n = 102
Comparator
Placebo
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
15 mg once weekly · subcutaneous · 28 weeksAs given in this study (human).
Source sentences
Summary
On meal tolerance testing, tirzepatide significantly reduced glucose excursions (lower insulin and glucagon concentrations) compared with placebo, with effects on these variables being greater than with semaglutide.
2 context sentences(design, population, supporting numbers)
Summary · context
patients were randomly assigned (3:3:2) to subcutaneously receive either tirzepatide 15 mg, semaglutide 1 mg, or placebo once per week
Summary · context
Because of discontinuations and exclusions due to missing or unevaluable data, 39 patients in each treatment group and 24 patients in the placebo group comprised the pharmacodynamic analysis set.
Report a problemFND-3546832206
10HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, 13 (30%) patients on semaglutide 1 mg weekly reported nausea.
In plain wordsIn adults with type 2 diabetes, about three in ten people taking semaglutide reported nausea.
Peptide
Semaglutide
Outcome
Not applicableNausea (semaglutide arm)
Study
n = 44
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
1 mg · subcutaneous · 28 weeksAs given in this study (human).
Measurements
Nausea incidence
30%
semaglutide 1 mg
Source sentences
Summary
The safety profiles of tirzepatide and semaglutide were similar, with gastrointestinal adverse events being the most common (11 [24%], 13 [30%], and seven [25%] with nausea; nine [20%], 13 [30%], and six [21%] with diarrhoea; and three [7%], five [11%], and one [4%] with vomiting, for tirzepatide, s…
1 context sentence(design, population, supporting numbers)
Summary · context
Via a randomisation table, patients were randomly assigned (3:3:2) to subcutaneously receive either tirzepatide 15 mg, semaglutide 1 mg, or placebo once per week.
Report a problemFND-3546832209
11HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, 13 (30%) patients on semaglutide 1 mg weekly reported diarrhoea.
In plain wordsIn adults with type 2 diabetes, about three in ten people taking semaglutide reported diarrhoea.
Peptide
Semaglutide
Outcome
Not applicableDiarrhoea (semaglutide arm)
Study
n = 44
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
1 mg · subcutaneous · 28 weeksAs given in this study (human).
Measurements
Diarrhoea incidence
30%
semaglutide 1 mg
Source sentences
Summary
The safety profiles of tirzepatide and semaglutide were similar, with gastrointestinal adverse events being the most common (11 [24%], 13 [30%], and seven [25%] with nausea; nine [20%], 13 [30%], and six [21%] with diarrhoea; and three [7%], five [11%], and one [4%] with vomiting, for tirzepatide, s…
1 context sentence(design, population, supporting numbers)
Summary · context
Via a randomisation table, patients were randomly assigned (3:3:2) to subcutaneously receive either tirzepatide 15 mg, semaglutide 1 mg, or placebo once per week.
Report a problemFND-3546832210
12HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, five (11%) patients on semaglutide 1 mg weekly reported vomiting.
In plain wordsIn adults with type 2 diabetes, about one in ten people taking semaglutide reported vomiting.
Peptide
Semaglutide
Outcome
Not applicableVomiting (semaglutide arm)
Study
n = 44
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
1 mg · subcutaneous · 28 weeksAs given in this study (human).
Measurements
Vomiting incidence
11%
semaglutide 1 mg
Source sentences
Summary
The safety profiles of tirzepatide and semaglutide were similar, with gastrointestinal adverse events being the most common (11 [24%], 13 [30%], and seven [25%] with nausea; nine [20%], 13 [30%], and six [21%] with diarrhoea; and three [7%], five [11%], and one [4%] with vomiting, for tirzepatide, s…
1 context sentence(design, population, supporting numbers)
Summary · context
Via a randomisation table, patients were randomly assigned (3:3:2) to subcutaneously receive either tirzepatide 15 mg, semaglutide 1 mg, or placebo once per week.
Report a problemFND-3546832211

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 1Results postedNCT03951753

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

Eli Lilly and Companyn = 11728 Jun 2019 to 8 Apr 2021

Diabetes Mellitus, Type 2

Trial page ClinicalTrials.govUpdated 20 Mar 2023

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 3 to 38Current
28 Oct 2026, 02:04 UTC
The same notice was added 36 times, first on 9 Oct 2026, 12:39 UTC. The status did not change between them.
Study results updated
Version 2
9 Oct 2026, 03:07 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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