Optimal dose of tirzepatide for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis.

Yu Y, Hu G, Yin S, Yang X, Zhou M, Jian W

Frontiers in cardiovascular medicine31 Aug 2022Cited by 15 (Europe PMC)

PMID36119737PMCIDPMC9472131DOI10.3389/fcvm.2022.990182PepBankPUB-36119737

Summary

ObjectiveThe purpose of this study is to evaluate the optimal dose of tirzepatide (TZP) for the treatment of type 2 diabetes mellitus (T2DM) by meta-analysis and trial sequential analysis (TSA).MethodsClinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022. Mean differences (MD) and 95% confidence intervals (95%CI) were used for continuous variables, and relative risk (RR) and 95%CI were used for dichotomous variables.ResultsCompared with TZP 5 mg, meta-analysis showed that TZP 10 mg significantly reduced glycosylated hemoglobin type A1c (HbA1c) (MD -0.24, 95%CI -0.31~-0.17, P < 0.00001), fasting serum glucose (FSG) (MD -5.82, 95%CI -8.35~-3.28, P < 0.00001) and weight (MD -2.47, 95%CI -2.95~-1.98, P < 0.00001), and TZP 15 mg significantly reduced HbA1c (MD -0.37, 95%CI -0.44~-0.29, P < 0.00001), FSG (MD -8.52, 95%CI -11.07~-5.98, P < 0.00001) and weight (MD -4.63, 95%CI -5.45~-3.81, P < 0.00001). Compared with TZP 10 mg, TZP 15 mg dramatically reduced HbA1c (MD -0.12, 95%CI -0.19~-0.05, P = 0.001), FSG (MD -2.73, 95%CI -5.29~-0.17, P = 0.04) and weight (MD -2.18, 95%CI -2.67~-1.70, P < 0.00001). The TSA indicated that the benefits observed in the current information set were conclusive, except for the FSG of "TZP 15 mg vs. TZP 10 mg". In terms of safety endpoints, meta-analysis revealed that there was no significant difference in the serious adverse events (AEs), major adverse cardiovascular events-4 (MACE-4), cardiovascular death, hypertension, cancer and hypoglycemic of the three dose groups of TZP. Compared with TZP 5 mg, TZP 10 mg increased total adverse events (RR 1.06, 95%CI 1.01~1.11, P = 0.03) and gastrointestinal (GI) AEs (RR 1.17, 95%CI 1.03~1.33, P = 0.02), and TZP 15 mg increased total AEs (RR 1.10, 95%CI 1.05~1.15, P = 0.0001). There were no significant differences in total AEs and GI AEs for TZP 15 mg compared to TZP 10 mg. The TSA demonstrated that the total AEs of "TZP 15 mg vs. TZP 5 mg" were conclusive.ConclusionsTZP 15 mg >TZP 10 mg > TZP 5 mg in terms of lowering glycemia and reducing weight. TZP 5 mg > TZP 10 mg = TZP 15 mg in terms of safety. On this basis, we recommend TZP 5 mg as the first-choice dose for patients with T2DM to minimize AEs while reducing glycemia and weight. If patients cannot effectively control their glycemia after taking TZP 5 mg, it is recommended to take TZP 15 mg directly to achieve the best effect of glycemic reduction. However, most of the included studies have the background of basic medication, the independent efficacy and safety of different doses of TZP still need to be tested.Systematic review registrationUnique Identifier: CRD42022341966.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study20

20 results from studies that gave the peptide. 20 results from people.

01HumanSystematic reviewEfficacy outcome
In a meta-analysis of trials in type 2 diabetes, tirzepatide 10 mg reduced HbA1c more than tirzepatide 5 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 10 mg lowered HbA1c more than 5 mg.
Peptide
Tirzepatide
Outcome
DecreaseHbA1c, 10 mg vs 5 mg
Study
n: not reported in source
Comparator
Tirzepatide 5 mg
Outcome group
Glycemic control · Metabolic and weight
Studied dose
10 mgAs given in this study (human).
Source sentences
Summary
TZP 10 mg significantly reduced glycosylated hemoglobin type A1c (HbA1c) (MD -0.24, 95%CI -0.31~-0.17, P < 0.00001)
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973701
02HumanSystematic reviewEfficacy outcome
In a meta-analysis of trials in type 2 diabetes, tirzepatide 10 mg reduced fasting serum glucose more than tirzepatide 5 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 10 mg lowered fasting blood glucose more than 5 mg.
Peptide
Tirzepatide
Outcome
DecreaseFasting serum glucose, 10 mg vs 5 mg
Study
n: not reported in source
Comparator
Tirzepatide 5 mg
Outcome group
Glycemic control · Metabolic and weight
Studied dose
10 mgAs given in this study (human).
Source sentences
Summary
fasting serum glucose (FSG) (MD -5.82, 95%CI -8.35~-3.28, P < 0.00001)
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973702
03HumanSystematic reviewEfficacy outcome
In a meta-analysis of trials in type 2 diabetes, tirzepatide 10 mg reduced weight more than tirzepatide 5 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 10 mg reduced weight more than 5 mg.
Peptide
Tirzepatide
Outcome
DecreaseWeight, 10 mg vs 5 mg
Study
n: not reported in source
Comparator
Tirzepatide 5 mg
Outcome group
Body weight · Metabolic and weight
Studied dose
10 mgAs given in this study (human).
Source sentences
Summary
weight (MD -2.47, 95%CI -2.95~-1.98, P < 0.00001)
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973703
04HumanSystematic reviewEfficacy outcome
In a meta-analysis of trials in type 2 diabetes, tirzepatide 15 mg reduced HbA1c more than tirzepatide 5 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 15 mg lowered HbA1c more than 5 mg.
Peptide
Tirzepatide
Outcome
DecreaseHbA1c, 15 mg vs 5 mg
Study
n: not reported in source
Comparator
Tirzepatide 5 mg
Outcome group
Glycemic control · Metabolic and weight
Studied dose
15 mgAs given in this study (human).
Source sentences
Summary
TZP 15 mg significantly reduced HbA1c (MD -0.37, 95%CI -0.44~-0.29, P < 0.00001)
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973704
05HumanSystematic reviewEfficacy outcome
In a meta-analysis of trials in type 2 diabetes, tirzepatide 15 mg reduced fasting serum glucose more than tirzepatide 5 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 15 mg lowered fasting blood glucose more than 5 mg.
Peptide
Tirzepatide
Outcome
DecreaseFasting serum glucose, 15 mg vs 5 mg
Study
n: not reported in source
Comparator
Tirzepatide 5 mg
Outcome group
Glycemic control · Metabolic and weight
Studied dose
15 mgAs given in this study (human).
Source sentences
Summary
FSG (MD -8.52, 95%CI -11.07~-5.98, P < 0.00001)
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973705
06HumanSystematic reviewEfficacy outcome
In a meta-analysis of trials in type 2 diabetes, tirzepatide 15 mg reduced weight more than tirzepatide 5 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 15 mg reduced weight more than 5 mg.
Peptide
Tirzepatide
Outcome
DecreaseWeight, 15 mg vs 5 mg
Study
n: not reported in source
Comparator
Tirzepatide 5 mg
Outcome group
Body weight · Metabolic and weight
Studied dose
15 mgAs given in this study (human).
Source sentences
Summary
weight (MD -4.63, 95%CI -5.45~-3.81, P < 0.00001)
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973706
07HumanSystematic reviewEfficacy outcome
In a meta-analysis of trials in type 2 diabetes, tirzepatide 15 mg reduced HbA1c more than tirzepatide 10 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 15 mg lowered HbA1c more than 10 mg.
Peptide
Tirzepatide
Outcome
DecreaseHbA1c, 15 mg vs 10 mg
Study
n: not reported in source
Comparator
Tirzepatide 10 mg
Outcome group
Glycemic control · Metabolic and weight
Studied dose
15 mgAs given in this study (human).
Source sentences
Summary
Compared with TZP 10 mg, TZP 15 mg dramatically reduced HbA1c (MD -0.12, 95%CI -0.19~-0.05, P = 0.001), FSG (MD -2.73, 95%CI -5.29~-0.17, P = 0.04) and weight (MD -2.18, 95%CI -2.67~-1.70, P < 0.00001).
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973707
08HumanSystematic reviewEfficacy outcome
In a meta-analysis of trials in type 2 diabetes, tirzepatide 15 mg reduced fasting serum glucose more than tirzepatide 10 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 15 mg lowered fasting blood glucose more than 10 mg.
Peptide
Tirzepatide
Outcome
DecreaseFasting serum glucose, 15 mg vs 10 mg
Study
n: not reported in source
Comparator
Tirzepatide 10 mg
Outcome group
Glycemic control · Metabolic and weight
Studied dose
15 mgAs given in this study (human).
Source sentences
Summary
Compared with TZP 10 mg, TZP 15 mg dramatically reduced HbA1c (MD -0.12, 95%CI -0.19~-0.05, P = 0.001), FSG (MD -2.73, 95%CI -5.29~-0.17, P = 0.04) and weight (MD -2.18, 95%CI -2.67~-1.70, P < 0.00001).
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973708
09HumanSystematic reviewEfficacy outcome
In a meta-analysis of trials in type 2 diabetes, tirzepatide 15 mg reduced weight more than tirzepatide 10 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 15 mg reduced weight more than 10 mg.
Peptide
Tirzepatide
Outcome
DecreaseWeight, 15 mg vs 10 mg
Study
n: not reported in source
Comparator
Tirzepatide 10 mg
Outcome group
Body weight · Metabolic and weight
Studied dose
15 mgAs given in this study (human).
Source sentences
Summary
Compared with TZP 10 mg, TZP 15 mg dramatically reduced HbA1c (MD -0.12, 95%CI -0.19~-0.05, P = 0.001), FSG (MD -2.73, 95%CI -5.29~-0.17, P = 0.04) and weight (MD -2.18, 95%CI -2.67~-1.70, P < 0.00001).
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973709
10HumanSystematic reviewSafety outcome
In a meta-analysis of trials in type 2 diabetes, serious adverse events did not differ significantly between the three tirzepatide doses.
In plain wordsIn adults with type 2 diabetes, serious side effects did not differ significantly between tirzepatide 5, 10 and 15 mg.
Peptide
Tirzepatide
Outcome
No significant changeSerious adverse events across doses
Study
n: not reported in source
Comparator
Other tirzepatide doses
Outcome group
Adverse events · Whole body
Studied dose
5, 10 or 15 mgAs given in this study (human).
Source sentences
Summary
In terms of safety endpoints, meta-analysis revealed that there was no significant difference in the serious adverse events (AEs), major adverse cardiovascular events-4 (MACE-4), cardiovascular death, hypertension, cancer and hypoglycemic of the three dose groups of TZP.
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973710
11HumanSystematic reviewSafety outcome
In a meta-analysis of trials in type 2 diabetes, major adverse cardiovascular events-4 did not differ significantly between the three tirzepatide doses.
In plain wordsIn adults with type 2 diabetes, major heart and vascular events did not differ significantly between tirzepatide 5, 10 and 15 mg.
Peptide
Tirzepatide
Outcome
No significant changeMACE-4 across doses
Study
n: not reported in source
Comparator
Other tirzepatide doses
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
5, 10 or 15 mgAs given in this study (human).
Source sentences
Summary
In terms of safety endpoints, meta-analysis revealed that there was no significant difference in the serious adverse events (AEs), major adverse cardiovascular events-4 (MACE-4), cardiovascular death, hypertension, cancer and hypoglycemic of the three dose groups of TZP.
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973711
12HumanSystematic reviewSafety outcome
In a meta-analysis of trials in type 2 diabetes, cardiovascular death did not differ significantly between the three tirzepatide doses.
In plain wordsIn adults with type 2 diabetes, deaths from heart and vascular causes did not differ significantly between tirzepatide 5, 10 and 15 mg.
Peptide
Tirzepatide
Outcome
No significant changeCardiovascular death across doses
Study
n: not reported in source
Comparator
Other tirzepatide doses
Outcome group
Mortality · Cardiovascular
Studied dose
5, 10 or 15 mgAs given in this study (human).
Source sentences
Summary
In terms of safety endpoints, meta-analysis revealed that there was no significant difference in the serious adverse events (AEs), major adverse cardiovascular events-4 (MACE-4), cardiovascular death, hypertension, cancer and hypoglycemic of the three dose groups of TZP.
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973712
13HumanSystematic reviewSafety outcome
In a meta-analysis of trials in type 2 diabetes, hypertension did not differ significantly between the three tirzepatide doses.
In plain wordsIn adults with type 2 diabetes, high blood pressure events did not differ significantly between tirzepatide 5, 10 and 15 mg.
Peptide
Tirzepatide
Outcome
No significant changeHypertension across doses
Study
n: not reported in source
Comparator
Other tirzepatide doses
Outcome group
Adverse events · Cardiovascular
Studied dose
5, 10 or 15 mgAs given in this study (human).
Source sentences
Summary
In terms of safety endpoints, meta-analysis revealed that there was no significant difference in the serious adverse events (AEs), major adverse cardiovascular events-4 (MACE-4), cardiovascular death, hypertension, cancer and hypoglycemic of the three dose groups of TZP.
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973713
14HumanSystematic reviewSafety outcome
In a meta-analysis of trials in type 2 diabetes, cancer did not differ significantly between the three tirzepatide doses.
In plain wordsIn adults with type 2 diabetes, cancer events did not differ significantly between tirzepatide 5, 10 and 15 mg.
Peptide
Tirzepatide
Outcome
No significant changeCancer across doses
Study
n: not reported in source
Comparator
Other tirzepatide doses
Outcome group
Adverse events · Cancer
Studied dose
5, 10 or 15 mgAs given in this study (human).
Source sentences
Summary
In terms of safety endpoints, meta-analysis revealed that there was no significant difference in the serious adverse events (AEs), major adverse cardiovascular events-4 (MACE-4), cardiovascular death, hypertension, cancer and hypoglycemic of the three dose groups of TZP.
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973714
15HumanSystematic reviewSafety outcome
In a meta-analysis of trials in type 2 diabetes, hypoglycemia did not differ significantly between the three tirzepatide doses.
In plain wordsIn adults with type 2 diabetes, low blood sugar events did not differ significantly between tirzepatide 5, 10 and 15 mg.
Peptide
Tirzepatide
Outcome
No significant changeHypoglycemia across doses
Study
n: not reported in source
Comparator
Other tirzepatide doses
Outcome group
Adverse events · Metabolic and weight
Studied dose
5, 10 or 15 mgAs given in this study (human).
Source sentences
Summary
In terms of safety endpoints, meta-analysis revealed that there was no significant difference in the serious adverse events (AEs), major adverse cardiovascular events-4 (MACE-4), cardiovascular death, hypertension, cancer and hypoglycemic of the three dose groups of TZP.
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973715
16HumanSystematic reviewSafety outcome
In a meta-analysis of trials in type 2 diabetes, tirzepatide 10 mg increased total adverse events compared with tirzepatide 5 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 10 mg caused more side effects overall than 5 mg.
Peptide
Tirzepatide
Outcome
IncreaseTotal adverse events, 10 mg vs 5 mg
Study
n: not reported in source
Comparator
Tirzepatide 5 mg
Outcome group
Adverse events · Whole body
Studied dose
10 mgAs given in this study (human).
Measurements
RR
1.06 ratio
total AEs, 10 mg vs 5 mg
Source sentences
Summary
Compared with TZP 5 mg, TZP 10 mg increased total adverse events (RR 1.06, 95%CI 1.01~1.11, P = 0.03) and gastrointestinal (GI) AEs (RR 1.17, 95%CI 1.03~1.33, P = 0.02), and TZP 15 mg increased total AEs (RR 1.10, 95%CI 1.05~1.15, P = 0.0001).
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973716
17HumanSystematic reviewSafety outcome
In a meta-analysis of trials in type 2 diabetes, tirzepatide 10 mg increased gastrointestinal adverse events compared with tirzepatide 5 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 10 mg caused more gut side effects than 5 mg.
Peptide
Tirzepatide
Outcome
IncreaseGastrointestinal adverse events, 10 mg vs 5 mg
Study
n: not reported in source
Comparator
Tirzepatide 5 mg
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
10 mgAs given in this study (human).
Measurements
RR
1.17 ratio
GI AEs, 10 mg vs 5 mg
Source sentences
Summary
Compared with TZP 5 mg, TZP 10 mg increased total adverse events (RR 1.06, 95%CI 1.01~1.11, P = 0.03) and gastrointestinal (GI) AEs (RR 1.17, 95%CI 1.03~1.33, P = 0.02), and TZP 15 mg increased total AEs (RR 1.10, 95%CI 1.05~1.15, P = 0.0001).
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973717
18HumanSystematic reviewSafety outcome
In a meta-analysis of trials in type 2 diabetes, tirzepatide 15 mg increased total adverse events compared with tirzepatide 5 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 15 mg caused more side effects overall than 5 mg.
Peptide
Tirzepatide
Outcome
IncreaseTotal adverse events, 15 mg vs 5 mg
Study
n: not reported in source
Comparator
Tirzepatide 5 mg
Outcome group
Adverse events · Whole body
Studied dose
15 mgAs given in this study (human).
Measurements
RR
1.1 ratio
total AEs, 15 mg vs 5 mg
Source sentences
Summary
Compared with TZP 5 mg, TZP 10 mg increased total adverse events (RR 1.06, 95%CI 1.01~1.11, P = 0.03) and gastrointestinal (GI) AEs (RR 1.17, 95%CI 1.03~1.33, P = 0.02), and TZP 15 mg increased total AEs (RR 1.10, 95%CI 1.05~1.15, P = 0.0001).
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973718
19HumanSystematic reviewSafety outcome
In a meta-analysis of trials in type 2 diabetes, total adverse events did not differ significantly between tirzepatide 15 mg and 10 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 15 mg and 10 mg caused similar numbers of side effects overall.
Peptide
Tirzepatide
Outcome
No significant changeTotal adverse events, 15 mg vs 10 mg
Study
n: not reported in source
Comparator
Tirzepatide 10 mg
Outcome group
Adverse events · Whole body
Studied dose
15 mgAs given in this study (human).
Source sentences
Summary
There were no significant differences in total AEs and GI AEs for TZP 15 mg compared to TZP 10 mg.
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973719
20HumanSystematic reviewSafety outcome
In a meta-analysis of trials in type 2 diabetes, gastrointestinal adverse events did not differ significantly between tirzepatide 15 mg and 10 mg.
In plain wordsIn adults with type 2 diabetes, tirzepatide 15 mg and 10 mg caused similar numbers of gut side effects.
Peptide
Tirzepatide
Outcome
No significant changeGastrointestinal adverse events, 15 mg vs 10 mg
Study
n: not reported in source
Comparator
Tirzepatide 10 mg
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
15 mgAs given in this study (human).
Source sentences
Summary
There were no significant differences in total AEs and GI AEs for TZP 15 mg compared to TZP 10 mg.
1 context sentence(design, population, supporting numbers)
Summary · context
Clinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022.
Show in the study text Report a problemFND-3611973720

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.

Version 2Current
12 Oct 2026, 12:58 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.

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Keywords

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