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Study · Systematic review · n = 6,609 · 2022

14 results

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis.

Karagiannis T, Avgerinos I, Liakos A, Del Prato S, Matthews DR, Tsapas A, Bekiari E

Diabetologia17 May 2022Cited by 191 (Europe PMC)

PMID35579691 (opens in a new tab)PMCIDPMC9112245 (opens in a new tab)DOI10.1007/s00125-022-05715-4 (opens in a new tab)PepBankPUB-35579691
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Summary

Aims/hypothesisTirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) currently under review for marketing approval. Individual trials have assessed the clinical profile of tirzepatide vs different comparators. We conducted a systematic review and meta-analysis to assess the efficacy and safety of tirzepatide for type 2 diabetes.MethodsWe searched PubMed, Embase, Cochrane and ClinicalTrials.gov up until 27 October 2021 for randomised controlled trials with a duration of at least 12 weeks that compared once-weekly tirzepatide 5, 10 or 15 mg with placebo or other glucose-lowering drugs in adults with type 2 diabetes irrespective of their background glucose-lowering treatment. The primary outcome was change in HbA1c from baseline. Secondary efficacy outcomes included change in body weight, proportion of individuals reaching the HbA1c target of <53 mmol/mol (<7.0%), ≤48 mmol/mol (≤6.5%) or <39 mmol/mol (<5.7%), and proportion of individuals with body weight loss of at least 5%, 10% or 15%. Safety outcomes included hypoglycaemia, gastrointestinal adverse events, treatment discontinuation due to adverse events, serious adverse events, and mortality. We used version 2 of the Cochrane risk-of-bias tool for randomised trials to assess risk of bias for the primary outcome.ResultsSeven trials (6609 participants) were included. A dose-dependent superiority in lowering HbA1c was evident with all three tirzepatide doses vs all comparators, with mean differences ranging from -17.71 mmol/mol (-1.62%) to -22.35 mmol/mol (-2.06%) vs placebo, -3.22 mmol/mol (-0.29%) to -10.06 mmol/mol (-0.92%) vs GLP-1 RAs, and -7.66 mmol/mol (-0.70%) to -12.02 mmol/mol (-1.09%) vs basal insulin regimens. Tirzepatide was more efficacious in reducing body weight; reductions vs GLP-1 RAs ranged from 1.68 kg with tirzepatide 5 mg to 7.16 kg with tirzepatide 15 mg. Incidence of hypoglycaemia with tirzepatide was similar vs placebo and lower vs basal insulin. Nausea was more frequent with tirzepatide vs placebo, especially with tirzepatide 15 mg (OR 5.60 [95% CI 3.12, 10.06]), associated with higher incidence of vomiting (OR 5.50 [95% CI 2.40, 12.59]) and diarrhoea (OR 3.31 [95% CI 1.40, 7.85]). Odds of gastrointestinal events were similar between tirzepatide and GLP-1 RAs, except for diarrhoea with tirzepatide 10 mg (OR 1.51 [95% CI 1.07, 2.15]). Tirzepatide 15 mg led to higher discontinuation rate of study medication due to adverse events regardless of comparator, while all tirzepatide doses were safe in terms of serious adverse events and mortality.Conclusions/interpretationA dose-dependent superiority on glycaemic efficacy and body weight reduction was evident with tirzepatide vs placebo, GLP-1 RAs and basal insulin. Tirzepatide did not increase the odds of hypoglycaemia but was associated with increased incidence of gastrointestinal adverse events. Study limitations include presence of statistical heterogeneity in the meta-analyses for change in HbA1c and body weight, assessment of risk of bias solely for the primary outcome, and generalisation of findings mainly to individuals who are overweight or obese and already on metformin-based background therapy. PROSPERO registration no. CRD42021283449.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study14

14 results from studies that gave the peptide. 14 results from people.

  1. 01HumanSystematic reviewEfficacy outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, once-weekly tirzepatide 5, 10 or 15 mg lowered HbA1c more than placebo, with mean differences from -17.71 to -22.35 mmol/mol (-1.62% to -2.06%).

    In plain wordsIn pooled trials of adults with type 2 diabetes, tirzepatide lowered long-term blood sugar (HbA1c) more than placebo.

    Peptide
    Tirzepatide
    Outcome
    DecreaseChange in HbA1c vs placebo
    Study

    n = 6,609

    Comparator
    Placebo
    Analysis
    Primary
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    5, 10 or 15 mg once weekly · Included trials lasted at least 12 weeksAs given in this study (human).

    Measurements

    Mean difference in HbA1c change vs placebo (reduction, range across doses)
    17.71 to 22.35 mmol/mol
    tirzepatide 5-15 mg vs placebo
    Mean difference in HbA1c change vs placebo (reduction, range across doses)
    1.62 to 2.06%
    tirzepatide 5-15 mg vs placebo

    Source sentences

    Summary
    A dose-dependent superiority in lowering HbA1c was evident with all three tirzepatide doses vs all comparators, with mean differences ranging from -17.71 mmol/mol (-1.62%) to -22.35 mmol/mol (-2.06%) vs placebo
    1 context sentence
    Summary · context
    Seven trials (6609 participants) were included.
  2. 02HumanSystematic reviewEfficacy outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, tirzepatide lowered HbA1c more than GLP-1 receptor agonists, with mean differences from -3.22 to -10.06 mmol/mol (-0.29% to -0.92%).

    In plain wordsIn pooled trials of adults with type 2 diabetes, tirzepatide lowered long-term blood sugar (HbA1c) more than other GLP-1 receptor agonist drugs.

    Peptide
    Tirzepatide
    Outcome
    DecreaseChange in HbA1c vs GLP-1 receptor agonists
    Study

    n = 6,609

    Comparator
    GLP-1 receptor agonists (individual drugs not named)
    Analysis
    Primary
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    5, 10 or 15 mg once weekly · Included trials lasted at least 12 weeksAs given in this study (human).

    Measurements

    Mean difference in HbA1c change vs GLP-1 RAs (reduction, range across doses)
    3.22 to 10.06 mmol/mol
    tirzepatide 5-15 mg vs GLP-1 RAs
    Mean difference in HbA1c change vs GLP-1 RAs (reduction, range across doses)
    0.29 to 0.92%
    tirzepatide 5-15 mg vs GLP-1 RAs

    Source sentences

    Summary
    -3.22 mmol/mol (-0.29%) to -10.06 mmol/mol (-0.92%) vs GLP-1 RAs
    2 context sentences
    Summary · context
    A dose-dependent superiority in lowering HbA1c was evident with all three tirzepatide doses vs all comparators
    Summary · context
    Seven trials (6609 participants) were included.
  3. 03HumanSystematic reviewEfficacy outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, tirzepatide lowered HbA1c more than basal insulin regimens, with mean differences from -7.66 to -12.02 mmol/mol (-0.70% to -1.09%).

    In plain wordsIn pooled trials of adults with type 2 diabetes, tirzepatide lowered long-term blood sugar (HbA1c) more than basal insulin.

    Peptide
    Tirzepatide
    Outcome
    DecreaseChange in HbA1c vs basal insulin regimens
    Study

    n = 6,609

    Comparator
    Basal insulin regimens
    Analysis
    Primary
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    5, 10 or 15 mg once weekly · Included trials lasted at least 12 weeksAs given in this study (human).

    Measurements

    Mean difference in HbA1c change vs basal insulin (reduction, range across doses)
    7.66 to 12.02 mmol/mol
    tirzepatide 5-15 mg vs basal insulin
    Mean difference in HbA1c change vs basal insulin (reduction, range across doses)
    0.7 to 1.09%
    tirzepatide 5-15 mg vs basal insulin

    Source sentences

    Summary
    -7.66 mmol/mol (-0.70%) to -12.02 mmol/mol (-1.09%) vs basal insulin regimens
    2 context sentences
    Summary · context
    A dose-dependent superiority in lowering HbA1c was evident with all three tirzepatide doses vs all comparators
    Summary · context
    Seven trials (6609 participants) were included.
  4. 04HumanSystematic reviewEfficacy outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, tirzepatide reduced body weight more than GLP-1 receptor agonists, by 1.68 kg (5 mg) to 7.16 kg (15 mg).

    In plain wordsIn pooled trials of adults with type 2 diabetes, tirzepatide reduced body weight more than other GLP-1 receptor agonist drugs.

    Peptide
    Tirzepatide
    Outcome
    DecreaseBody weight change vs GLP-1 receptor agonists
    Study

    n = 6,609

    Comparator
    GLP-1 receptor agonists (individual drugs not named)
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    5, 10 or 15 mg once weekly · Included trials lasted at least 12 weeksAs given in this study (human).

    Measurements

    Body weight reduction vs GLP-1 RAs (range across doses)
    1.68 to 7.16 kg
    tirzepatide 5 mg to 15 mg vs GLP-1 RAs

    Source sentences

    Summary
    Tirzepatide was more efficacious in reducing body weight; reductions vs GLP-1 RAs ranged from 1.68 kg with tirzepatide 5 mg to 7.16 kg with tirzepatide 15 mg
    1 context sentence
    Summary · context
    Seven trials (6609 participants) were included.
  5. 05HumanSystematic reviewSafety outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, hypoglycaemia incidence with tirzepatide was similar to placebo.

    In plain wordsIn pooled trials of adults with type 2 diabetes, low blood sugar events were about as common with tirzepatide as with placebo.

    Peptide
    Tirzepatide
    Outcome
    No significant changeHypoglycaemia incidence vs placebo
    Study

    n = 6,609

    Comparator
    Placebo
    Outcome group
    Adverse events · Metabolic and weight
    Studied dose
    5, 10 or 15 mg once weekly · Included trials lasted at least 12 weeksAs given in this study (human).

    Source sentences

    Summary
    Incidence of hypoglycaemia with tirzepatide was similar vs placebo and lower vs basal insulin
    1 context sentence
    Summary · context
    Seven trials (6609 participants) were included.
  6. 06HumanSystematic reviewSafety outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, hypoglycaemia incidence with tirzepatide was lower than with basal insulin regimens.

    In plain wordsIn pooled trials of adults with type 2 diabetes, low blood sugar events were less common with tirzepatide than with basal insulin.

    Peptide
    Tirzepatide
    Outcome
    DecreaseHypoglycaemia incidence vs basal insulin
    Study

    n = 6,609

    Comparator
    Basal insulin regimens
    Outcome group
    Adverse events · Metabolic and weight
    Studied dose
    5, 10 or 15 mg once weekly · Included trials lasted at least 12 weeksAs given in this study (human).

    Source sentences

    Summary
    Incidence of hypoglycaemia with tirzepatide was similar vs placebo and lower vs basal insulin
    1 context sentence
    Summary · context
    Seven trials (6609 participants) were included.
  7. 07HumanSystematic reviewSafety outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, nausea was more frequent with tirzepatide than with placebo, especially at 15 mg (OR 5.60, 95% CI 3.12 to 10.06).

    In plain wordsIn pooled trials of adults with type 2 diabetes, nausea was more common with tirzepatide than with placebo, especially at 15 mg.

    Peptide
    Tirzepatide
    Outcome
    IncreaseNausea vs placebo
    Study

    n = 6,609

    Comparator
    Placebo
    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    15 mg once weekly (highest-dose result) · Included trials lasted at least 12 weeksAs given in this study (human).

    Measurements

    Odds ratio for nausea
    5.6
    tirzepatide 15 mg vs placebo
    95% CI of odds ratio for nausea
    3.12 to 10.06
    tirzepatide 15 mg vs placebo

    Source sentences

    Summary
    Nausea was more frequent with tirzepatide vs placebo, especially with tirzepatide 15 mg (OR 5.60 [95% CI 3.12, 10.06])
    1 context sentence
    Summary · context
    Seven trials (6609 participants) were included.
  8. 08HumanSystematic reviewSafety outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, vomiting was more frequent with tirzepatide than with placebo (OR 5.50, 95% CI 2.40 to 12.59).

    In plain wordsIn pooled trials of adults with type 2 diabetes, vomiting was more common with tirzepatide than with placebo.

    Peptide
    Tirzepatide
    Outcome
    IncreaseVomiting vs placebo
    Study

    n = 6,609

    Comparator
    Placebo
    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    5, 10 or 15 mg once weekly · Included trials lasted at least 12 weeksAs given in this study (human).

    Measurements

    Odds ratio for vomiting
    5.5
    tirzepatide vs placebo
    95% CI of odds ratio for vomiting
    2.4 to 12.59
    tirzepatide vs placebo

    Source sentences

    Summary
    associated with higher incidence of vomiting (OR 5.50 [95% CI 2.40, 12.59])
    2 context sentences
    Summary · context
    Nausea was more frequent with tirzepatide vs placebo
    Summary · context
    Seven trials (6609 participants) were included.
  9. 09HumanSystematic reviewSafety outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, diarrhoea was more frequent with tirzepatide than with placebo (OR 3.31, 95% CI 1.40 to 7.85).

    In plain wordsIn pooled trials of adults with type 2 diabetes, diarrhoea was more common with tirzepatide than with placebo.

    Peptide
    Tirzepatide
    Outcome
    IncreaseDiarrhoea vs placebo
    Study

    n = 6,609

    Comparator
    Placebo
    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    5, 10 or 15 mg once weekly · Included trials lasted at least 12 weeksAs given in this study (human).

    Measurements

    Odds ratio for diarrhoea
    3.31
    tirzepatide vs placebo
    95% CI of odds ratio for diarrhoea
    1.4 to 7.85
    tirzepatide vs placebo

    Source sentences

    Summary
    and diarrhoea (OR 3.31 [95% CI 1.40, 7.85])
    2 context sentences
    Summary · context
    Nausea was more frequent with tirzepatide vs placebo
    Summary · context
    Seven trials (6609 participants) were included.
  10. 10HumanSystematic reviewSafety outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, odds of gastrointestinal adverse events were similar between tirzepatide and GLP-1 receptor agonists, except for diarrhoea with 10 mg.

    In plain wordsIn pooled trials of adults with type 2 diabetes, stomach and gut side effects were mostly similar with tirzepatide and other GLP-1 receptor agonist drugs.

    Peptide
    Tirzepatide
    Outcome
    No significant changeGastrointestinal events vs GLP-1 receptor agonists
    Study

    n = 6,609

    Comparator
    GLP-1 receptor agonists (individual drugs not named)
    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    5, 10 or 15 mg once weekly · Included trials lasted at least 12 weeksAs given in this study (human).

    Source sentences

    Summary
    Odds of gastrointestinal events were similar between tirzepatide and GLP-1 RAs, except for diarrhoea with tirzepatide 10 mg (OR 1.51 [95% CI 1.07, 2.15]).
    1 context sentence
    Summary · context
    Seven trials (6609 participants) were included.
  11. 11HumanSystematic reviewSafety outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, diarrhoea was more frequent with tirzepatide 10 mg than with GLP-1 receptor agonists (OR 1.51, 95% CI 1.07 to 2.15).

    In plain wordsIn pooled trials of adults with type 2 diabetes, diarrhoea was more common with tirzepatide 10 mg than with other GLP-1 receptor agonist drugs.

    Peptide
    Tirzepatide
    Outcome
    IncreaseDiarrhoea with tirzepatide 10 mg vs GLP-1 receptor agonists
    Study

    n = 6,609

    Comparator
    GLP-1 receptor agonists (individual drugs not named)
    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    10 mg once weekly · Included trials lasted at least 12 weeksAs given in this study (human).

    Measurements

    Odds ratio for diarrhoea
    1.51
    tirzepatide 10 mg vs GLP-1 RAs
    95% CI of odds ratio for diarrhoea
    1.07 to 2.15
    tirzepatide 10 mg vs GLP-1 RAs

    Source sentences

    Summary
    except for diarrhoea with tirzepatide 10 mg (OR 1.51 [95% CI 1.07, 2.15])
    2 context sentences
    Summary · context
    Odds of gastrointestinal events were similar between tirzepatide and GLP-1 RAs
    Summary · context
    Seven trials (6609 participants) were included.
  12. 12HumanSystematic reviewSafety outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, tirzepatide 15 mg led to a higher rate of study-medication discontinuation due to adverse events regardless of comparator.

    In plain wordsIn pooled trials of adults with type 2 diabetes, more people stopped tirzepatide 15 mg because of side effects than stopped comparator treatments.

    Peptide
    Tirzepatide
    Outcome
    IncreaseTreatment discontinuation due to adverse events (15 mg)
    Study

    n = 6,609

    Comparator
    All comparators (placebo, GLP-1 receptor agonists, basal insulin)
    Outcome group
    Adverse events · Whole body
    Studied dose
    15 mg once weekly · Included trials lasted at least 12 weeksAs given in this study (human).

    Source sentences

    Summary
    Tirzepatide 15 mg led to higher discontinuation rate of study medication due to adverse events regardless of comparator
    1 context sentence
    Summary · context
    Seven trials (6609 participants) were included.
  13. 13HumanSystematic reviewSafety outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, the authors reported that all tirzepatide doses were safe in terms of serious adverse events.

    In plain wordsThe authors of this pooled analysis of trials in type 2 diabetes described all tirzepatide doses as safe for serious side effects.

    Peptide
    Tirzepatide
    Outcome
    Direction not reportedSerious adverse events
    Study

    n = 6,609

    Outcome group
    Adverse events · Whole body
    Studied dose
    5, 10 or 15 mg once weekly · Included trials lasted at least 12 weeksAs given in this study (human).

    Source sentences

    Summary
    all tirzepatide doses were safe in terms of serious adverse events and mortality
    1 context sentence
    Summary · context
    Seven trials (6609 participants) were included.
  14. 14HumanSystematic reviewSafety outcome

    In a meta-analysis of seven randomised trials in adults with type 2 diabetes, the authors reported that all tirzepatide doses were safe in terms of mortality.

    In plain wordsThe authors of this pooled analysis of trials in type 2 diabetes described all tirzepatide doses as safe for deaths.

    Peptide
    Tirzepatide
    Outcome
    Direction not reportedMortality
    Study

    n = 6,609

    Outcome group
    Mortality · Whole body
    Studied dose
    5, 10 or 15 mg once weekly · Included trials lasted at least 12 weeksAs given in this study (human).

    Source sentences

    Summary
    all tirzepatide doses were safe in terms of serious adverse events and mortality
    1 context sentence
    Summary · context
    Seven trials (6609 participants) were included.

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

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. Version 2Current

    9 Oct 2026, 12:39 UTC

    Study results updated

  2. 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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