TRIAL RESULTS · SIDE EFFECTS
Setmelanotide side effects
ANSWER
In 6 placebo-controlled trials with posted results, the most common side effects of Setmelanotide were skin hyperpigmentation 36.9% (placebo 7.7%), nausea 29.6% (placebo 14.5%), injection site erythema 23.0% (placebo 20.0%). Read from ClinicalTrials.gov on 2026-10-03. Not medical advice.
Trial register
Trials with posted results
8
with an arm on Setmelanotide, of 29 registered
Against placebo
6
placebo-controlled trials
People in those trials
355
on Setmelanotide · 207 on placebo
Read
2026-10-03
ClinicalTrials.gov
VS PLACEBO
Most common side effects, Setmelanotide beside placebo
Share of people with each side effect in 6 placebo-controlled trials with posted results: 355 people on Setmelanotide (all doses), 207 on placebo, same trials. Listed only when reported for at least half of the people on Setmelanotide. Source: ClinicalTrials.gov, read 2026-10-03. Not medical advice.
ALL TRIALS
The 100 most reported of 981 side effects reported
Every trial with posted results and an arm on Setmelanotide (n ≥ 20), all phases, by people affected. Placebo is shown where placebo-controlled trials reported the same event. Comparator arms are not counted.
| Side effect | Organ system | Setmelanotide | Placebo | Trials |
|---|---|---|---|---|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | 48.4% (268 of 554) | 7.7% | 7 |
| Nausea | Gastrointestinal disorders | 27.9% (212 of 759) | 14.5% | 8 |
| Headache | Nervous system disorders | 23.3% (177 of 759) | 18.4% | 8 |
| Vomiting | Gastrointestinal disorders | 18.5% (136 of 737) | 10.7% | 7 |
| Injection site erythema | General disorders | 26.3% (136 of 517) | 20.0% | 6 |
| Skin Hyperpigmentation | Skin and subcutaneous tissue disorders | 53.7% (110 of 205) | - | 1 |
| Injection site pain | General disorders | 19.1% (99 of 517) | 21.2% | 6 |
| Injection site pruritus | General disorders | 17.5% (97 of 554) | 11.6% | 7 |
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 18.8% (86 of 458) | 3.2% | 6 |
| Diarrhoea | Gastrointestinal disorders | 11.0% (81 of 737) | 10.7% | 7 |
| Fatigue | General disorders | 11.0% (81 of 737) | 7.5% | 7 |
| Injection site induration | General disorders | 15.1% (78 of 517) | 8.2% | 6 |
| Nasopharyngitis | Infections and infestations | 9.8% (62 of 634) | 6.2% | 6 |
| Covid-19 | Infections and infestations | 29.3% (60 of 205) | - | 1 |
| Injection Site Erythema | General disorders | 21.0% (43 of 205) | - | 1 |
| Dizziness | Nervous system disorders | 5.7% (41 of 722) | 4.7% | 7 |
| Melanocytic Naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 20.0% (41 of 205) | - | 1 |
| Cough | Respiratory, thoracic and mediastinal disorders | 5.7% (40 of 700) | 6.7% | 6 |
| Injection site oedema | General disorders | 9.5% (40 of 421) | 4.1% | 5 |
| Injection Site Pruritus | General disorders | 18.5% (38 of 205) | - | 1 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 5.0% (37 of 737) | 1.6% | 7 |
| Injection site bruising | General disorders | 8.7% (37 of 423) | 12.3% | 5 |
| Decreased appetite | Metabolism and nutrition disorders | 7.9% (36 of 455) | 1.9% | 5 |
| Upper Respiratory Tract Infection | Infections and infestations | 17.6% (36 of 205) | - | 1 |
| Injection Site Induration | General disorders | 17.1% (35 of 205) | - | 1 |
| Abdominal pain | Gastrointestinal disorders | 6.4% (34 of 532) | 5.3% | 6 |
| Influenza | Infections and infestations | 6.6% (33 of 498) | 10.4% | 3 |
| Injection site reaction | General disorders | 8.2% (32 of 392) | 14.0% | 4 |
| Pyrexia | General disorders | 5.3% (28 of 527) | 7.9% | 4 |
| Gastroenteritis | Infections and infestations | 4.8% (27 of 564) | 3.5% | 5 |
| Constipation | Gastrointestinal disorders | 4.2% (26 of 623) | 6.4% | 5 |
| Upper respiratory tract infection | Infections and infestations | 7.2% (26 of 359) | 15.9% | 4 |
| Injection Site Pain | General disorders | 12.7% (26 of 205) | - | 1 |
| Injection Site Bruising | General disorders | 12.2% (25 of 205) | - | 1 |
| Injection site swelling | General disorders | 5.2% (23 of 440) | 8.3% | 5 |
| Rash | Skin and subcutaneous tissue disorders | 3.2% (21 of 660) | 3.1% | 6 |
| Depression | Psychiatric disorders | 3.5% (20 of 564) | 2.7% | 5 |
| Insomnia | Psychiatric disorders | 4.4% (20 of 455) | 0.0% | 4 |
| Abdominal pain upper | Gastrointestinal disorders | 5.0% (20 of 399) | 6.9% | 4 |
| Abdominal Pain Upper | Gastrointestinal disorders | 9.8% (20 of 205) | - | 1 |
| Abdominal Pain | Gastrointestinal disorders | 9.8% (20 of 205) | - | 1 |
| Back Pain | Musculoskeletal and connective tissue disorders | 9.8% (20 of 205) | - | 1 |
| Back pain | Musculoskeletal and connective tissue disorders | 3.4% (19 of 554) | 1.9% | 7 |
| Myalgia | Musculoskeletal and connective tissue disorders | 3.6% (19 of 527) | 6.6% | 4 |
| COVID-19 | Infections and infestations | 6.5% (19 of 293) | 10.4% | 2 |
| Pruritus | Skin and subcutaneous tissue disorders | 3.4% (18 of 529) | 1.3% | 4 |
| Urinary Tract Infection | Infections and infestations | 8.3% (17 of 205) | - | 1 |
| Disturbance in sexual arousal | Psychiatric disorders | 4.9% (16 of 324) | 0.0% | 3 |
| Acne | Skin and subcutaneous tissue disorders | 3.2% (16 of 500) | 2.0% | 3 |
| Libido increased | Psychiatric disorders | 7.2% (16 of 221) | 0.0% | 2 |
| Injection Site Oedema | General disorders | 7.8% (16 of 205) | - | 1 |
| Pain In Extremity | Musculoskeletal and connective tissue disorders | 7.8% (16 of 205) | - | 1 |
| Hypertension | Vascular disorders | 2.7% (15 of 557) | 0.0% | 5 |
| Ephelides | Skin and subcutaneous tissue disorders | 2.9% (15 of 522) | 1.4% | 4 |
| Alopecia | Skin and subcutaneous tissue disorders | 3.5% (15 of 433) | 0.0% | 3 |
| Spontaneous penile erection | Reproductive system and breast disorders | 4.3% (14 of 327) | 0.0% | 4 |
| Erection increased | Reproductive system and breast disorders | 3.9% (14 of 357) | 3.5% | 4 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 4.3% (14 of 322) | 5.3% | 3 |
| Dry skin | Skin and subcutaneous tissue disorders | 3.0% (13 of 436) | 2.9% | 5 |
| Anaemia | Blood and lymphatic system disorders | 2.5% (13 of 518) | 1.6% | 4 |
| Sinusitis | Infections and infestations | 2.6% (13 of 498) | 14.6% | 3 |
| Alanine Aminotransferase Increased | Investigations | 6.3% (13 of 205) | - | 1 |
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | 6.3% (13 of 205) | - | 1 |
| Migraine | Nervous system disorders | 2.8% (12 of 433) | 0.0% | 3 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 2.8% (12 of 433) | 3.6% | 3 |
| Pneumonia | Infections and infestations | 3.7% (12 of 328) | 5.3% | 3 |
| Pigmentation lip | Gastrointestinal disorders | 3.8% (12 of 317) | 0.0% | 3 |
| Eczema | Skin and subcutaneous tissue disorders | 3.0% (12 of 404) | - | 2 |
| Fall | Injury, poisoning and procedural complications | 3.0% (12 of 404) | - | 2 |
| Ear Infection | Infections and infestations | 5.9% (12 of 205) | - | 1 |
| Injection Site Haemorrhage | General disorders | 5.9% (12 of 205) | - | 1 |
| Dysmenorrhoea | Reproductive system and breast disorders | 1.9% (11 of 588) | 2.2% | 6 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 2.5% (11 of 436) | 5.1% | 5 |
| Anxiety | Psychiatric disorders | 2.3% (11 of 470) | 0.0% | 4 |
| Pain | General disorders | 2.5% (11 of 433) | 0.0% | 3 |
| Bronchitis | Infections and infestations | 2.5% (11 of 433) | 3.6% | 3 |
| Influenza like illness | General disorders | 3.5% (11 of 315) | 5.9% | 3 |
| Tongue Pigmentation | Gastrointestinal disorders | 5.4% (11 of 205) | - | 1 |
| Blood Creatine Phosphokinase Increased | Investigations | 5.4% (11 of 205) | - | 1 |
| Immunisation Reaction | Injury, poisoning and procedural complications | 5.4% (11 of 205) | - | 1 |
| Dyspepsia | Gastrointestinal disorders | 1.7% (10 of 588) | 0.7% | 6 |
| Pharyngitis | Infections and infestations | 2.3% (10 of 433) | 0.0% | 3 |
| Injection site discolouration | General disorders | 3.2% (10 of 317) | 1.4% | 3 |
| Acanthosis Nigricans | Skin and subcutaneous tissue disorders | 4.9% (10 of 205) | - | 1 |
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | 4.9% (10 of 205) | - | 1 |
| Vulvovaginal discomfort | Reproductive system and breast disorders | 5.0% (10 of 199) | - | 1 |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | 3.1% (9 of 287) | 0.0% | 4 |
| Viral Upper Respiratory Tract Infection | Infections and infestations | 4.4% (9 of 205) | - | 1 |
| Depressed Mood | Psychiatric disorders | 4.4% (9 of 205) | - | 1 |
| Skin discolouration | Skin and subcutaneous tissue disorders | 2.8% (8 of 287) | 0.0% | 4 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 3.1% (8 of 256) | 4.3% | 4 |
| Conjunctivitis | Eye disorders | 1.5% (8 of 527) | 3.9% | 4 |
| Urinary tract infection | Infections and infestations | 2.4% (8 of 330) | 3.5% | 3 |
| Urticaria | Skin and subcutaneous tissue disorders | 1.8% (8 of 441) | 0.0% | 3 |
| Contusion | Injury, poisoning and procedural complications | 3.4% (8 of 234) | 0.0% | 2 |
| Hidradenitis | Skin and subcutaneous tissue disorders | 2.0% (8 of 404) | - | 2 |
| Dry Skin | Skin and subcutaneous tissue disorders | 3.9% (8 of 205) | - | 1 |
| Erection Increased | Reproductive system and breast disorders | 3.9% (8 of 205) | - | 1 |
| Cellulitis | Infections and infestations | 1.3% (7 of 557) | 1.0% | 5 |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 1.2% (7 of 606) | 3.9% | 5 |
Source: ClinicalTrials.gov posted results, read 2026-10-03. A trial lists events above its own reporting threshold, so a rare event may be missing from some trials. Not medical advice.
FDA LABEL
What the FDA label says
Imcivree NDA213793 · label of 2026-04-01 Regulator
Most common adverse reactions (incidence ≥20% in at least 1 indication) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.
QUESTIONS
Does setmelanotide cause skin hyperpigmentation?
In 6 placebo-controlled trials with posted results, 36.9% of people on setmelanotide reported skin hyperpigmentation, against 7.7% on placebo. Source: ClinicalTrials.gov, read 2026-10-03. Not medical advice.
Does setmelanotide cause nausea?
In 6 placebo-controlled trials with posted results, 29.6% of people on setmelanotide reported nausea, against 14.5% on placebo. Source: ClinicalTrials.gov, read 2026-10-03. Not medical advice.
Does setmelanotide cause injection site erythema?
In 6 placebo-controlled trials with posted results, 23.0% of people on setmelanotide reported injection site erythema, against 20.0% on placebo. Source: ClinicalTrials.gov, read 2026-10-03. Not medical advice.
Does setmelanotide cause vomiting?
In 6 placebo-controlled trials with posted results, 21.3% of people on setmelanotide reported vomiting, against 10.7% on placebo. Source: ClinicalTrials.gov, read 2026-10-03. Not medical advice.
Does setmelanotide cause headache?
In 6 placebo-controlled trials with posted results, 19.7% of people on setmelanotide reported headache, against 18.4% on placebo. Source: ClinicalTrials.gov, read 2026-10-03. Not medical advice.
REGISTERED STUDIES
29 registered clinical trials of Setmelanotide
The 10 most recently updated are listed.
| NCT05774756 | A Trial of Setmelanotide in Acquired Hypothalamic Obesity Status: ACTIVE_NOT_RECRUITING · Updated 2026-08-10 |
|---|---|
| NCT05093634 | EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway Status: COMPLETED · Updated 2026-08-06 |
| NCT07496463 | Setmelanotide to Treat Obesity in a Patient With Pseudohypoparathyroidism Type 1a (PHP1a) Status: ENROLLING_BY_INVITATION · Updated 2026-07-23 |
| NCT06596135 | Open-Label Extension Study of Setmelanotide Status: COMPLETED · Updated 2026-07-15 |
| NCT07674290 | Real-World Effects of MC4R Agonist Therapy in BBS and Severe Genetic Obesity Status: RECRUITING · Updated 2026-06-29 |
| NCT06760546 | A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756) Status: RECRUITING · Updated 2026-02-12 |
| NCT06772597 | A Study of Setmelanotide in Patients With Prader-Willi Syndrome Status: ACTIVE_NOT_RECRUITING · Updated 2026-02-12 |
| 2023-507634-24-00 | A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial: Multiple Independent Sub-studies of Setmelanotide in Patients with POMC/PCSK1, LEPR, NCOA1 (SRC1), or SH2B1 Gene Variants in the Melanocortin-4 Receptor Pathway Status: UNKNOWN · Updated 2025-11-28 |
| NCT04963231 | DAYBREAK: A Study of Setmelanotide in Participants With Specific Gene Variants in the Melanocortin-4 Receptor (MC4R) Pathway Status: COMPLETED · Updated 2025-07-02 |
| NCT03651765 | Long Term Extension Trial of Setmelanotide Status: COMPLETED · Updated 2025-05-31 |
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