Peptide Comparison

SetmelanotidevsLiraglutide

Targeted MC4R agonist for rare genetic obesity caused by melanocortin pathway defects

FDA-approved once-daily GLP-1 receptor agonist (Victoza/Saxenda) that reduces HbA1c by 0.9–1.6%, promotes 5–10% body weight loss, and demonstrated a 13% reduction in major adverse cardiovascular events in the landmark LEADER trial of 9,340 patients

Weight ManagementWeight Management

At a Glance

Quick
comparison

Dose Range

Setmelanotide

0.5 mg–3 mg mg

Liraglutide

0.6–3.0 mg

Frequency

Setmelanotide

Once daily

Liraglutide

Once daily

Administration

Setmelanotide

subcutaneous injection

Liraglutide

Subcutaneous injection

Cycle Length

Setmelanotide

Ongoing/indefinite

Liraglutide

Ongoing/indefinite

Onset Speed

Setmelanotide

Moderate (1-2 weeks)

Liraglutide

Gradual (3-4 weeks)

Evidence Level

Setmelanotide

Strong human trials (Phase 3 or FDA approved)

Liraglutide

Strong human trials (Phase 3 or FDA approved)

Efficacy

Benefit
ratings

Setmelanotide

Liraglutide

Weight Management

Setmelanotide9%

Liraglutide9%

Metabolic Health

Setmelanotide8%

Liraglutide0%

Quality of Life

Setmelanotide8%

Liraglutide0%

Metabolic

Setmelanotide0%

Liraglutide9%

Healing & Recovery

Setmelanotide0%

Liraglutide8%

Technical Data

Compound
specifications

Setmelanotide

Molecular Formula

C₄₉H₆₈N₁₈O₉S₂

Molecular Weight

1,117.3 Da

Half-Life

~11 hours

Bioavailability

~79% subcutaneous bioavailability

CAS Number

920014-72-8

Liraglutide

Molecular Formula

C₁₇₂H₂₆₅N₄₃O₅₁

Molecular Weight

3,751 Da

Half-Life

~13 hours (enabling once-daily dosing); Tmax 8–12 hours; steady state in 3–5 days

Bioavailability

~55% after subcutaneous injection; >98% plasma protein binding to albumin via C16 fatty acid moiety

CAS Number

204656-20-2

Protocols

Dosing
tiers

Setmelanotide

Liraglutide

starting

0.6 mg subcutaneous once daily

Once daily

1 week (tolerability assessment)

Begin at 0.6 mg daily for the first week to assess gastrointestinal tolerability before dose escalation. This starting dose is sub-therapeutic for both diabetes and obesity indications. Inject in abdomen, thigh, or upper arm at any time of day regardless of meals. Rotate injection sites. GI side effects (nausea) are most common during the initial titration period.

standard

1.2–1.8 mg subcutaneous once daily

Once daily

Ongoing chronic therapy

Standard therapeutic dose range for type 2 diabetes (Victoza). Escalate from 0.6 mg to 1.2 mg at week 2 and optionally to 1.8 mg at week 3 for additional glycemic benefit. Maximum diabetes dose is 1.8 mg/day. No dose adjustment needed for renal or hepatic impairment. If combining with sulfonylureas, reduce sulfonylurea dose by 50% to minimize hypoglycemia. Store in-use pen at room temperature or refrigerated for up to 30 days.

advanced

3.0 mg subcutaneous once daily

Once daily

Ongoing chronic therapy with 16-week efficacy assessment

Obesity dose (Saxenda) reached through weekly 0.6 mg increments: 0.6→1.2→1.8→2.4→3.0 mg over 5 weeks. Evaluate response at 16 weeks — if <4% body weight loss, consider discontinuation as unlikely to achieve meaningful benefit. Must be combined with reduced-calorie diet and increased physical activity. Approved for BMI ≥30 or BMI ≥27 with weight-related comorbidities. Do not use simultaneously with Victoza or any other GLP-1 RA.

Applications

Best
suited for

Setmelanotide

Treating obesity caused by confirmed POMC deficiency mutations

Setmelanotide is particularly well-suited for individuals focused on treating obesity caused by confirmed pomc deficiency mutations. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Managing obesity from PCSK1 or LEPR genetic defects

Setmelanotide is particularly well-suited for individuals focused on managing obesity from pcsk1 or lepr genetic defects. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Reducing hyperphagia and body weight in Bardet-Biedl syndrome

Setmelanotide is particularly well-suited for individuals focused on reducing hyperphagia and body weight in bardet-biedl syndrome. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Addressing early-onset severe obesity with identified melanocortin pathway mutations

Setmelanotide is particularly well-suited for individuals focused on addressing early-onset severe obesity with identified melanocortin pathway mutations. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Liraglutide

Type 2 diabetes patients with HbA1c >7% requiring both glycemic control and weight management

Liraglutide is particularly well-suited for individuals focused on type 2 diabetes patients with hba1c >7% requiring both glycemic control and weight management. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Obese individuals (BMI ≥30) or overweight (BMI ≥27) with weight-related comorbidities seeking FDA-approved pharmacotherapy

Liraglutide is particularly well-suited for individuals focused on obese individuals (bmi ≥30) or overweight (bmi ≥27) with weight-related comorbidities seeking fda-approved pharmacotherapy. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Patients with established cardiovascular disease or high cardiovascular risk seeking cardioprotective diabetes therapy

Liraglutide is particularly well-suited for individuals focused on patients with established cardiovascular disease or high cardiovascular risk seeking cardioprotective diabetes therapy. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Patients on metformin requiring add-on therapy with favorable weight and cardiovascular profile

Liraglutide is particularly well-suited for individuals focused on patients on metformin requiring add-on therapy with favorable weight and cardiovascular profile. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.

Safety Profile

Side
effects

Setmelanotide

Common

Skin Hyperpigmentation
Injection Site Reactions
Nausea
Diarrhea

Uncommon

Hair Color Darkening and Nevus Changes

Serious

Depression and Suicidal Ideation

Liraglutide

Common

Nausea
Diarrhea
Vomiting
Decreased appetite and headache

Uncommon

Injection site reactions

Serious

Acute pancreatitis
Gallbladder disease

Research Status

Safety
& evidence

Setmelanotide

Evidence Level

Strong human trials (Phase 3 or FDA approved)

FDA Status

FDA approved for this use

Safety Overview

Setmelanotide demonstrates favorable tolerability in Phase 3 trials with safety data from over 200 patients across POMC, PCSK1, LEPR-deficient, and Bardet-Biedl syndrome populations. The most common adverse effect is dose-dependent skin hyperpigmentation (>60% of patients) due to off-target MC1R activation on melanocytes—a manageable, reversible pharmacological effect rather than true toxicity. Serious psychiatric adverse events including depression and suicidal ideation require baseline mental health screening and ongoing monitoring in all patients.

Contraindications

xKnown hypersensitivity to setmelanotide or any excipients
xObesity not caused by POMC, PCSK1, LEPR deficiency or Bardet-Biedl syndrome
xPatients without genetic confirmation of melanocortin pathway mutations
xUse during pregnancy (animal studies suggest potential fetal harm)

Liraglutide

Evidence Level

Strong human trials (Phase 3 or FDA approved)

FDA Status

FDA approved for this use

Safety Overview

Liraglutide (Victoza, Saxenda) is FDA-approved with extensive safety data from 15+ years of clinical use in diabetes (GLP-1 agonist) and obesity indications. Gastrointestinal side effects (nausea, vomiting, diarrhea) occur in 30-40% of patients during dose escalation but diminish significantly after 2-3 weeks of stable dosing. Black box warnings include risk of medullary thyroid carcinoma and pancreatitis, though absolute incidence remains rare. Injection site reactions are minimal. The compound shows no hepatotoxicity, nephrotoxicity, or major drug interactions at approved doses.

Contraindications

xPersonal or family history of medullary thyroid carcinoma (MTC) — black box warning based on rodent thyroid C-cell tumor findings
xMultiple Endocrine Neoplasia syndrome type 2 (MEN 2)
xKnown hypersensitivity to liraglutide or any excipients
xPregnancy (Saxenda indication) — contraindicated; effective contraception required

Decision Guide

Which is
right for you?

Choose Setmelanotide if...

Treating obesity caused by confirmed POMC deficiency mutations
Managing obesity from PCSK1 or LEPR genetic defects
Reducing hyperphagia and body weight in Bardet-Biedl syndrome
Addressing early-onset severe obesity with identified melanocortin pathway mutations

Choose Liraglutide if...

Type 2 diabetes patients with HbA1c >7% requiring both glycemic control and weight management
Obese individuals (BMI ≥30) or overweight (BMI ≥27) with weight-related comorbidities seeking FDA-approved pharmacotherapy
Patients with established cardiovascular disease or high cardiovascular risk seeking cardioprotective diabetes therapy
Patients on metformin requiring add-on therapy with favorable weight and cardiovascular profile

Full Setmelanotide Profile Full Liraglutide Profile

Peptide Database

Quickcomparison

Benefitratings

Compoundspecifications

Dosingtiers

Bestsuited for

Sideeffects

Safety& evidence

Which isright for you?

Quick
comparison

Benefit
ratings

Compound
specifications

Dosing
tiers

Best
suited for

Side
effects

Safety
& evidence

Which is
right for you?