Peptide Protocol IQ

Interaction explorer

Select two or more compounds or medication classes. Every unordered pair is evaluated against a curated register. This is a database lookup, not a generated answer, and A paired with B always returns the same result as B paired with A.

The single most important thing on this page

An identified interaction does not establish that a combination is harmful, and the absence of an identified interaction does not establish that a combination is safe. For most compounds in this catalogue, no interaction study has ever been performed, so “no qualifying signal identified” usually means nobody has looked.

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Includes catalogued compounds and the medication classes that appear in the register.

1
Pairs evaluated
1
Pairs with a caution or higher
0
Pairs with no qualifying signal

Semaglutide ↔ Tirzepatide

Mechanistic overlap3Significant research concernEMechanisticNo human evidence
Mechanism
Both agonise the GLP-1 receptor. Combining them stacks the same pharmacological action rather than adding a distinct one.
Rationale
Redundant receptor agonism with additive gastrointestinal and gastric-emptying effects. No trial has studied these two agents together, and neither product's labelling contemplates concurrent use.
Overlap domains
GLP-1 receptor agonism, Gastric emptying, Appetite signalling
Evidence certainty
High confidence. Certainty is reported separately from severity, because a serious hypothetical concern and a well-established mild one are different things.
Regulatory source
FDA-approved labelling for both products
Limitations
No study has evaluated the combination. The concern is mechanistic redundancy, which is a reasoning-based conclusion rather than an observed interaction.
Supporting sources (2)
Randomised controlled trialHuman Identifier verified

Once-Weekly Semaglutide in Adults with Overweight or Obesity

Wilding JPH, Batterham RL, Calanna S, et al. · New England Journal of Medicine · 2021 · n = 1,961

Population
Adults with BMI ≥30, or ≥27 with at least one weight-related coexisting condition; without diabetes
Endpoint
Percentage change in body weight and weight reduction of ≥5%
Route
Subcutaneous
Quantity as reported
2.4 mg weekly (16-week escalation from 0.25 mg)
Frequency
Once weekly
Duration
68 weeks

Result. Mean change in body weight was −14.9% with semaglutide versus −2.4% with placebo at week 68.

Adverse events. Nausea and diarrhoea were the most common events, typically transient and dose-escalation related; more discontinuations for gastrointestinal events than placebo.

Limitations. Participants without diabetes only; all participants received lifestyle intervention; 68-week duration does not address longer-term maintenance or discontinuation effects.

PMID33567185DOI10.1056/NEJMoa2032183NCTNCT03548935
Randomised controlled trialHuman Identifier verified

Tirzepatide Once Weekly for the Treatment of Obesity

Jastreboff AM, Aronne LJ, Ahmad NN, et al. · New England Journal of Medicine · 2022 · n = 2,539

Population
Adults with BMI ≥30, or ≥27 with a weight-related complication; without diabetes
Endpoint
Percentage change in body weight at week 72
Route
Subcutaneous
Quantity as reported
5 mg, 10 mg, or 15 mg weekly
Frequency
Once weekly
Duration
72 weeks

Result. Mean percentage weight change was −15.0%, −19.5%, and −20.9% at 5 mg, 10 mg, and 15 mg respectively, versus −3.1% with placebo.

Adverse events. Predominantly gastrointestinal (nausea, diarrhoea, constipation, vomiting), mostly mild to moderate and occurring during escalation.

Limitations. Excluded participants with diabetes; lifestyle intervention in all arms; does not establish durability after discontinuation.

PMID35658024DOI10.1056/NEJMoa2206038NCTNCT04184622