Semaglutide vs tirzepatide

Semaglutide acts on the GLP-1 receptor, and tirzepatide acts on both the GIP and GLP-1 receptors. Both are approved in the US and EU for type 2 diabetes and weight management, and both have large trial programs in people. This page compares their study results.

Best randomized result by outcome

For each outcome that two or more peptides have results for: the best result of a single randomized trial, on the same measure (the same kind of number, the same unit). When a trial has several dose arms, the cell shows the highest dose arm. The trials differ in people, length and dose, so a gap between two cells is not proof that one peptide works better.

Best randomized result by outcome for Semaglutide, Tirzepatide
Outcome	Semaglutide	Tirzepatide
Cardiovascular eventsCardiovascularCompared as: value in the arm that got the peptide, in %	12% Event rate Placebo: 13.8% Dose studied: maximal dose 14 mg once dailyn = 9,6502025	23.7% event rate Dose studied: up to 15 mg weeklymedian 46.9 monthsn = 13,1652026
Body weightMetabolic and weightCompared as: difference from placebo, in %	−2.54% Body weight change at 13 weeks Dose studied: maximum 14 mg once dailyn = 9,6502026	−19.4% Difference Dose studied: maximum tolerated dose (10 or 15 mg)52 weeksn = 6702024
Glycemic controlMetabolic and weightCompared as: value in the arm that got the peptide, in %	1.5 to 1.9% HbA1c change · semaglutide 1.0 mg, non-elderly Dose studied: 0.5 or 1.0 mg once weeklyn = 3,0452018	−2.3% HbA1c change · tirzepatide 5 mg Dose studied: 5 mg104 weeksn = 1,5002025
Blood pressureCardiovascularCompared as: difference from placebo, in mm hg	−3.9 mm Hg Systolic blood pressure difference Dose studied: 2.4 mg once weekly48 weeksn = 8032021	−6.8 mm Hg Net systolic blood pressure reduction · Shown as a change. The study reports a net systolic blood pressure reduction of this size. 72 weeksn not reported2024
Quality of lifeWhole bodyCompared as: value in the arm that got the peptide, in points	7.3 points Score change · semaglutide 7 mg Dose studied: 7 mg daily52 weeksn not reported2021	5.45 points General Health score change Dose studied: maximum tolerated dose72 weeksn not reported2026
Adverse eventsWhole bodyCompared as: value in the arm that got the peptide, in %	16.6% discontinuation due to adverse events Placebo: 8.2% Dose studied: 2.4 mg once weeklyn = 17,6042023	6.3% discontinuation due to adverse events Placebo: 1.4% Dose studied: up to 15 mg once weeklyat least 52 weeksn = 7312025
Gastrointestinal adverse eventsGastrointestinalCompared as: value in the arm that got the peptide, in %	99.5% Non-serious GI AEs Dose studied: 2.4 mg once weekly68 weeksn = 2,1172022	42.5% GI adverse events Dose studied: up to 15 mg weeklymedian 46.9 monthsn = 13,1652026

Cardiovascular eventsCardiovascularCompared as: value in the arm that got the peptide, in %
- Semaglutide
  12%
  Event rate
  Placebo: 13.8%
  Dose studied: maximal dose 14 mg once dailyn = 9,6502025
- Tirzepatide
  23.7%
  event rate
  Dose studied: up to 15 mg weeklymedian 46.9 monthsn = 13,1652026
Body weightMetabolic and weightCompared as: difference from placebo, in %
- Semaglutide
  −2.54%
  Body weight change at 13 weeks
  Dose studied: maximum 14 mg once dailyn = 9,6502026
- Tirzepatide
  −19.4%
  Difference
  Dose studied: maximum tolerated dose (10 or 15 mg)52 weeksn = 6702024
Glycemic controlMetabolic and weightCompared as: value in the arm that got the peptide, in %
- Semaglutide
  1.5 to 1.9%
  HbA1c change · semaglutide 1.0 mg, non-elderly
  Dose studied: 0.5 or 1.0 mg once weeklyn = 3,0452018
- Tirzepatide
  −2.3%
  HbA1c change · tirzepatide 5 mg
  Dose studied: 5 mg104 weeksn = 1,5002025
Blood pressureCardiovascularCompared as: difference from placebo, in mm hg
- Semaglutide
  −3.9 mm Hg
  Systolic blood pressure difference
  Dose studied: 2.4 mg once weekly48 weeksn = 8032021
- Tirzepatide
  −6.8 mm Hg
  Net systolic blood pressure reduction · Shown as a change. The study reports a net systolic blood pressure reduction of this size.
  72 weeksn not reported2024
Quality of lifeWhole bodyCompared as: value in the arm that got the peptide, in points
- Semaglutide
  7.3 points
  Score change · semaglutide 7 mg
  Dose studied: 7 mg daily52 weeksn not reported2021
- Tirzepatide
  5.45 points
  General Health score change
  Dose studied: maximum tolerated dose72 weeksn not reported2026
Adverse eventsWhole bodyCompared as: value in the arm that got the peptide, in %
- Semaglutide
  16.6%
  discontinuation due to adverse events
  Placebo: 8.2%
  Dose studied: 2.4 mg once weeklyn = 17,6042023
- Tirzepatide
  6.3%
  discontinuation due to adverse events
  Placebo: 1.4%
  Dose studied: up to 15 mg once weeklyat least 52 weeksn = 7312025
Gastrointestinal adverse eventsGastrointestinalCompared as: value in the arm that got the peptide, in %
- Semaglutide
  99.5%
  Non-serious GI AEs
  Dose studied: 2.4 mg once weekly68 weeksn = 2,1172022
- Tirzepatide
  42.5%
  GI adverse events
  Dose studied: up to 15 mg weeklymedian 46.9 monthsn = 13,1652026

Outcomes with a randomized result for one peptide only (5 outcomes)

The other peptides have no randomized result on the same measure, so these results cannot be set side by side.

Outcomes with a randomized result for one peptide only: Semaglutide, Tirzepatide
Outcome	Semaglutide	Tirzepatide
Inflammation markersImmune and inflammationCompared as: difference from placebo, in %	−18.08% hsCRP change at 13 weeks Dose studied: maximum 14 mg once dailyn = 9,6502026	No comparable result 22 randomized-trial results measure it in another way or another unit.
LipidsCardiovascularCompared as: difference from placebo, in %	−7% Total cholesterol change at 13 weeks Dose studied: maximum 14 mg once dailyn = 9,6502026	No comparable result 31 randomized-trial results measure it in another way or another unit.
Cardiometabolic risk factorsMetabolic and weightCompared as: value in the arm that got the peptide, in %	−61.1% Relative risk score change Placebo: −12.9% Dose studied: 2.4 mg68 weeksn = 1,5832023	No comparable result 20 randomized-trial results measure it in another way or another unit.
Liver fat and liver functionLiverCompared as: difference from placebo, in percentage points	28.7 percentage points Estimated difference Dose studied: 2.4 mg once weekly72 weeks (interim analysis; planned 240 weeks)n = 8002025	No comparable result 15 randomized-trial results measure it in another way or another unit.
Heart functionCardiovascularCompared as: difference from placebo, in points	No comparable result 40 randomized-trial results measure it in another way or another unit.	6.9 points between-group difference Dose studied: up to 15 mg once weeklyat least 52 weeksn = 7312025

Inflammation markersImmune and inflammationCompared as: difference from placebo, in %
- Semaglutide
  −18.08%
  hsCRP change at 13 weeks
  Dose studied: maximum 14 mg once dailyn = 9,6502026
- Tirzepatide
  No comparable result
  22 randomized-trial results measure it in another way or another unit.
LipidsCardiovascularCompared as: difference from placebo, in %
- Semaglutide
  −7%
  Total cholesterol change at 13 weeks
  Dose studied: maximum 14 mg once dailyn = 9,6502026
- Tirzepatide
  No comparable result
  31 randomized-trial results measure it in another way or another unit.
Cardiometabolic risk factorsMetabolic and weightCompared as: value in the arm that got the peptide, in %
- Semaglutide
  −61.1%
  Relative risk score change
  Placebo: −12.9%
  Dose studied: 2.4 mg68 weeksn = 1,5832023
- Tirzepatide
  No comparable result
  20 randomized-trial results measure it in another way or another unit.
Liver fat and liver functionLiverCompared as: difference from placebo, in percentage points
- Semaglutide
  28.7 percentage points
  Estimated difference
  Dose studied: 2.4 mg once weekly72 weeks (interim analysis; planned 240 weeks)n = 8002025
- Tirzepatide
  No comparable result
  15 randomized-trial results measure it in another way or another unit.
Heart functionCardiovascularCompared as: difference from placebo, in points
- Semaglutide
  No comparable result
  40 randomized-trial results measure it in another way or another unit.
- Tirzepatide
  6.9 points
  between-group difference
  Dose studied: up to 15 mg once weeklyat least 52 weeksn = 7312025

Comparing 2 peptides · Data version 308560

Only differences

Swipe sideways to see every peptide.

Comparison of Semaglutide, Tirzepatide
Peptide	Synthetic analog Semaglutide	Synthetic analog Tirzepatide
Identity
Kind	Synthetic analog	Synthetic analog
Area	Weight and metabolic	Weight and metabolic
Evidence
Amount of evidence	4,624	2,165
Evidence level	Has results from studies in people	Has results from studies in people
Safety
Safety results	1,224 (1,221 in people)	462 (462 in people)
Status
Approval
Sport (WADA)
Registered trials	663 · 284 active124 more mention it but do not test it	254 · 162 active47 more mention it but do not test it

Shared outcomes

Body weight1490
Glycemic control1032
Adverse events988
Gastrointestinal adverse events524
Cardiovascular events422
Liver fat and liver function232
Lipids197
Kidney function176
Mortality167
Blood pressure150
Appetite and food intake117
Heart function116

Approval and sport status

From the regulatory data of each peptide.

Semaglutide
The FDA label for Ozempic says: “Adjunct to diet and exercise for glycemic control in adults with type 2 diabetes; reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease; reduce the risk of sustained eGFR decline…”
Tirzepatide
The FDA label for Mounjaro says: “Adjunct to diet and exercise for glycemic control in adults and pediatric patients 10 years and older with type 2 diabetes; reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes at high risk for these events”

Amount of evidence by outcome

Outcome groups with study results for at least two of these peptides. Counts include only results from studies that gave the peptide. Bar length is the number of results, on one scale. The bars show how much was studied, not how large an effect was. A peptide with more studies can look stronger here without being stronger. For results, see the randomized results above.

Study results per shared outcome group and evidence class
Outcome group	Semaglutide	Tirzepatide
Body weightMetabolic and weight	969954105	521501182
Glycemic controlMetabolic and weight	66866512	36435581
Adverse eventsWhole body	7757723	213213
Gastrointestinal adverse eventsGastrointestinal	345345	179179
Cardiovascular eventsWhole body	2672634	1551523
Liver fat and liver functionMusculoskeletal	17917441	5353
LipidsMetabolic and weight	1181171	79763
Kidney functionKidney and urinary	1361351	40391
MortalityWhole body	1041031	635724
Blood pressureEndocrine and hormones	9999	5151
Appetite and food intakeNervous system and cognition	97952	20191
Heart functionCardiovascular	67616	49427

Sequence alignment

Each analog against its native parent, residue by residue. Substitutions, non-standard residues and modifications are marked. Calculated from the two sequences.

Against Glucagon-like peptide 1 (7-37)Semaglutide

Semaglutide differs from Glucagon-like peptide 1 (7-37) at 2 positions and carries 1 added group.

Top row: Glucagon-like peptide 1 (7-37) (parent, numbered from 7)
Bottom row: Semaglutide

HEGTFTSDV

SSYLEGQAA

EFIAWLVGR

Same as parent
Substituted
Non-canonical or D-form
Modified side chain or end

What is different

1Position 8: Ala is replaced by Aib, an amino acid that is not one of the standard 20.
2Position 26: Lys carries an added group: lipidation.
3Position 34: Lys is replaced by Arg.

Against Gastric inhibitory polypeptide (GIP)Tirzepatide

Tirzepatide differs from Gastric inhibitory polypeptide (GIP) at 11 positions and in 1 end segment.

Top row: Gastric inhibitory polypeptide (GIP) (parent)
Bottom row: Tirzepatide

YEGTFSDY

SIDKIQ

FVWLA

PSSGAPPPS

Same as parent
Substituted
Non-canonical or D-form
Modified side chain or end
Replaced segment
Parent context

What is different

1Position 2: Ala is replaced by Aib, an amino acid that is not one of the standard 20.
2Position 7: Ile is replaced by Thr.
3Position 13: Ala is replaced by Aib, an amino acid that is not one of the standard 20.
4Position 14: Met is replaced by Leu.
5Position 18: His is replaced by Ala.
6Position 20: Gln is replaced by Lys.
7Position 21: Asp is replaced by Ala.
8Position 24: Asn is replaced by Gln.
9Position 27: Leu is replaced by Ile.
10Position 29: Gln is replaced by Gly.
11Position 30: Lys is replaced by Gly.
12Positions 31 to 39: the end of the peptide is a different stretch of amino acids, not a set of single swaps.

Trials side by side

Registered trials, ranked by phase (late phases first), then posted results and enrollment. Status is the registry status. Study results come from published studies. Results posted at ClinicalTrials.gov are shown on each trial page.

Semaglutide663 registered trials

Top 3 of 663 trials, ranked by phase, then posted results and enrollment: 3 completed · 3 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT03574597

Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity

Novo Nordisk A/S17,604 participants24 Oct 2018 to 29 Jun 2023

Overweight · Obesity

Trial page ClinicalTrials.gov

CompletedPhase 3Results postedNCT03914326

A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes

Novo Nordisk A/S9,651 participants17 Jun 2019 to 23 Aug 2024

Diabetes Mellitus, Type 2

Trial page ClinicalTrials.gov

CompletedPhase 3Results postedNCT03819153

A Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease

Novo Nordisk A/S3,533 participants17 Jun 2019 to 9 Jan 2024

Diabetes Mellitus, Type 2

Trial page ClinicalTrials.gov

124 more mention it but do not test it. They only measure it or name it in their text.

Tirzepatide254 registered trials

Top 3 of 254 trials, ranked by phase, then posted results and enrollment: 3 completed · 3 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT04255433