Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial.

Ludvik B, Giorgino F, Jódar E, Frias JP, Fernández Landó L, Brown K, Bray R, Rodríguez Á

Lancet (London, England)6 Aug 2021Cited by 501 (Europe PMC)

PMID34370970DOI10.1016/s0140-6736(21)01443-4PepBankPUB-34370970

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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: Publisher copyright. Results still quote short attributed sentences.

Results from this study7

7 results from studies that gave the peptide. 7 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on metformin, tirzepatide 5, 10 and 15 mg reduced HbA1c at week 52 by 1·93%, 2·20% and 2·37% versus 1·34% with insulin degludec; non-inferiority was met and treatment differences ranged from -0·59% to -1·04%.
In plain wordsIn adults with type 2 diabetes, tirzepatide lowered long-term blood sugar (HbA1c) more than insulin degludec after 52 weeks.
Peptide
Tirzepatide
Outcome
DecreaseHbA1c change from baseline at week 52
Study
n = 1,437
Comparator
Titrated insulin degludec (once daily, subcutaneous)
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
5 mg, 10 mg or 15 mg once weekly (start 2·5 mg, escalated by 2·5 mg every 4 weeks) · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
the reductions in HbA_1c at week 52 were 1·93% (SE 0·05) for tirzepatide 5 mg, 2·20% (0·05) for tirzepatide 10 mg, and 2·37% (0·05) for tirzepatide 15 mg, and 1·34% (0·05) for insulin degludec. The non-inferiority margin of 0·3% was met. The estimated treatment difference (ETD) versus insu…
1 context sentence(design, population, supporting numbers)
Summary · context
The modified intention-to-treat population was 1437 participants from the tirzepatide 5 mg (n=358), tirzepatide 10 mg (n=360), tirzepatide 15 mg (n=359), and insulin degludec (n=360) groups.
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02HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on metformin, a higher proportion of participants in all three tirzepatide groups than on insulin degludec reached an HbA1c below 7·0% at week 52.
In plain wordsIn adults with type 2 diabetes, more people reached the HbA1c goal of below 7% with tirzepatide than with insulin degludec.
Peptide
Tirzepatide
Outcome
IncreaseProportion with HbA1c below 7·0% at week 52
Study
n = 1,437
Comparator
Titrated insulin degludec (once daily, subcutaneous)
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
5 mg, 10 mg or 15 mg once weekly (start 2·5 mg, escalated by 2·5 mg every 4 weeks) · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
The proportion of participants achieving a HbA_1c of less than 7·0% (<53 mmol/mol) at week 52 was greater (p<0·0001) in all three tirzepatide groups (82%-93%) versus insulin degludec (61%).
1 context sentence(design, population, supporting numbers)
Summary · context
The modified intention-to-treat population was 1437 participants from the tirzepatide 5 mg (n=358), tirzepatide 10 mg (n=360), tirzepatide 15 mg (n=359), and insulin degludec (n=360) groups.
Report a problemFND-3437097002
03HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on metformin, all three tirzepatide doses decreased bodyweight at week 52 (by at least 7·5 kg) whereas insulin degludec increased it by 2·3 kg, with significantly larger reductions with tirzepatide.
In plain wordsIn adults with type 2 diabetes, tirzepatide led to weight loss after 52 weeks, while insulin degludec led to weight gain.
Peptide
Tirzepatide
Outcome
DecreaseBodyweight change from baseline at week 52
Study
n = 1,437
Comparator
Titrated insulin degludec (once daily, subcutaneous)
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
5 mg, 10 mg or 15 mg once weekly (start 2·5 mg, escalated by 2·5 mg every 4 weeks) · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
At week 52, from a baseline of 94·3 kg (SD 20·1), all three tirzepatide doses decreased bodyweight (-7·5 kg to -12·9 kg), whereas insulin degludec increased bodyweight by 2·3 kg. The ETD versus insulin degludec ranged from -9·8 kg to -15·2 kg for tirzepatide (p<0·0001 for all tirzepatide doses).
1 context sentence(design, population, supporting numbers)
Summary · context
The modified intention-to-treat population was 1437 participants from the tirzepatide 5 mg (n=358), tirzepatide 10 mg (n=360), tirzepatide 15 mg (n=359), and insulin degludec (n=360) groups.
Report a problemFND-3437097003
04HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes on metformin, nausea, diarrhoea, decreased appetite and vomiting were more frequent with tirzepatide than with insulin degludec (insulin degludec rates were 2%, 4%, 1% and 1% respectively), mostly mild to moderate.
In plain wordsIn adults with type 2 diabetes, nausea, diarrhoea, reduced appetite and vomiting were more common with tirzepatide than with insulin degludec, mostly mild to moderate.
Peptide
Tirzepatide
Outcome
IncreaseGastrointestinal adverse events (nausea, diarrhoea, decreased appetite, vomiting)
Study
n = 1,437
Comparator
Titrated insulin degludec (once daily, subcutaneous)
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
5 mg, 10 mg or 15 mg once weekly (start 2·5 mg, escalated by 2·5 mg every 4 weeks) · subcutaneous · 52 weeksAs given in this study (human).
Measurements
Nausea incidence
2%
insulin degludec
Diarrhoea incidence
15 to 17%
tirzepatide groups (range)
Diarrhoea incidence
4%
insulin degludec
Decreased appetite incidence
1%
insulin degludec
Vomiting incidence
1%
insulin degludec
Source sentences
Summary
A higher incidence of nausea (12-24%), diarrhoea (15-17%), decreased appetite (6-12%), and vomiting (6-10%) was reported in participants treated with tirzepatide than in those treated with insulin degludec (2%, 4%, 1%, and 1%, respectively).
2 context sentences(design, population, supporting numbers)
Summary · context
The most common adverse events in tirzepatide-treated participants were mild to moderate gastrointestinal events that decreased over time.
Summary · context
The modified intention-to-treat population was 1437 participants from the tirzepatide 5 mg (n=358), tirzepatide 10 mg (n=360), tirzepatide 15 mg (n=359), and insulin degludec (n=360) groups.
Report a problemFND-3437097004
05HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes on metformin, hypoglycaemia (defined in the trial by a low-glucose threshold or severity) occurred in 1%, 1% and 2% of participants on tirzepatide 5, 10 and 15 mg versus 7% on insulin degludec.
In plain wordsIn adults with type 2 diabetes, low blood sugar events were less common with tirzepatide than with insulin degludec.
Peptide
Tirzepatide
Outcome
DecreaseHypoglycaemia (<54 mg/dL or severe)
Study
n = 1,437
Comparator
Titrated insulin degludec (once daily, subcutaneous)
Outcome group
Adverse events · Metabolic and weight
Studied dose
5 mg, 10 mg or 15 mg once weekly (start 2·5 mg, escalated by 2·5 mg every 4 weeks) · subcutaneous · 52 weeksAs given in this study (human).
Measurements
Hypoglycaemia incidence
1%
tirzepatide 5 mg
Hypoglycaemia incidence
1%
tirzepatide 10 mg
Hypoglycaemia incidence
2%
tirzepatide 15 mg
Hypoglycaemia incidence
7%
insulin degludec
Source sentences
Summary
Hypoglycaemia (<54 mg/dL or severe) was reported in five (1%), four (1%), and eight (2%) participants on tirzepatide 5, 10, and 15 mg, respectively, versus 26 (7%) on insulin degludec.
1 context sentence(design, population, supporting numbers)
Summary · context
The modified intention-to-treat population was 1437 participants from the tirzepatide 5 mg (n=358), tirzepatide 10 mg (n=360), tirzepatide 15 mg (n=359), and insulin degludec (n=360) groups.
Report a problemFND-3437097005
06HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes on metformin, treatment discontinuation due to an adverse event was more common in the tirzepatide groups than in the insulin degludec group.
In plain wordsIn adults with type 2 diabetes, more people stopped tirzepatide because of side effects than stopped insulin degludec.
Peptide
Tirzepatide
Outcome
IncreaseTreatment discontinuation due to adverse events
Study
n = 1,437
Comparator
Titrated insulin degludec (once daily, subcutaneous)
Outcome group
Adverse events · Whole body
Studied dose
5 mg, 10 mg or 15 mg once weekly (start 2·5 mg, escalated by 2·5 mg every 4 weeks) · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
Treatment discontinuation due to an adverse event was more common in the tirzepatide groups than in the insulin degludec group.
1 context sentence(design, population, supporting numbers)
Summary · context
The modified intention-to-treat population was 1437 participants from the tirzepatide 5 mg (n=358), tirzepatide 10 mg (n=360), tirzepatide 15 mg (n=359), and insulin degludec (n=360) groups.
Report a problemFND-3437097006
07HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes, five participants died during the 52-week study, and the investigators considered none of the deaths related to study treatment.
In plain wordsIn this 52-week trial in type 2 diabetes, five people died; the investigators judged none of the deaths related to the study treatment.
Peptide
Tirzepatide
Outcome
Not applicableDeaths during the study
Study
n = 1,437
Outcome group
Mortality · Whole body
Studied dose
5 mg, 10 mg or 15 mg once weekly (start 2·5 mg, escalated by 2·5 mg every 4 weeks) · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
Five participants died during the study; none of the deaths were considered by the investigators to be related to the study treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
The modified intention-to-treat population was 1437 participants from the tirzepatide 5 mg (n=358), tirzepatide 10 mg (n=360), tirzepatide 15 mg (n=359), and insulin degludec (n=360) groups.
Report a problemFND-3437097007

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 3Results postedNCT03882970

A Study of Tirzepatide (LY3298176) Versus Insulin Degludec in Participants With Type 2 Diabetes

Eli Lilly and Companyn = 1,4441 Apr 2019 to 4 Jan 2021

Type 2 Diabetes Mellitus

Trial page ClinicalTrials.govUpdated 19 Jan 2022

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.

Version 2Current
9 Oct 2026, 12:39 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

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