Amycretin: Side Effects
Known side effects, contraindications, and interactions
📌TL;DR
- •5 known side effects documented
- •3 mild, 2 moderate, 0 severe
- •4 contraindications listed
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Side Effects Severity Chart
Most common GI adverse event. Reported in 82% of SC amycretin participants in Phase 1b/2a. Peaks during dose escalation and diminishes thereafter. Generally mild to moderate.
Reported in 53% of SC amycretin participants. More common during up-titration. Generally transient and mild to moderate.
Reported in 41% of SC amycretin participants. Generally mild to moderate and self-limiting.
Expected pharmacological effect of dual GLP-1/amylin receptor agonism. Common across all dose levels.
Reported with SC formulation. Generally mild and consistent with other injectable peptide therapies.
⛔Contraindications
- •Amycretin is investigational and not approved for any indication. Use only within clinical trials.
- •Expected GLP-1 agonist class contraindication: personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
- •Pregnancy (GLP-1 agonist class)
- •Prior serious hypersensitivity to amycretin or excipients
⚠️Drug Interactions
- •Insulin and sulfonylureas: Increased risk of hypoglycemia when combined (GLP-1 and amylin agonist class interaction)
- •Oral medications: Dual GLP-1/amylin activation produces additive gastric emptying delay, potentially affecting absorption of co-administered drugs
- •Oral contraceptives: Enhanced gastric emptying delay may reduce absorption; consider non-oral contraception
Community-Reported Side Effects
See which side effects community members report most frequently.
0View community protocolsSafety Overview#
Amycretin's safety profile has been characterized in Phase 1 (144 participants, oral) and Phase 1b/2a (125 participants, SC) trials published in The Lancet, plus a Phase 2 T2D trial (448 participants). As a dual GLP-1/amylin receptor agonist, amycretin produces GI adverse events consistent with both mechanisms. GI events were the most common TEAEs, with nausea in 82%, vomiting in 53%, and diarrhea in 41% of SC-treated participants.
Gastrointestinal Adverse Events#
The dual GLP-1/amylin mechanism produces additive effects on gastric emptying delay and central appetite suppression, resulting in higher GI event rates than selective GLP-1 agonists.
Phase 1b/2a Safety (SC, Obesity)#
- Nausea: 82% of amycretin participants
- Vomiting: 53%
- Diarrhea: 41%
- Timing: Peak during up-titration, diminishing thereafter
- Severity: Nearly all mild to moderate
- Dose-dependence: Higher GI rates at higher doses
Phase 1 Safety (Oral)#
- 62% of participants reported TEAEs (all mild or moderate)
- 49% of all TEAEs were GI-related (180 of 364 events)
- No deaths reported
Phase 2 Safety (T2D)#
- GI events consistent with incretin and amylin-based therapies
- Majority mild to moderate
Comparison with CagriSema#
Both amycretin and CagriSema target the same two pathways (GLP-1 + amylin). CagriSema reported GI events in 79.6% of participants in REDEFINE 1. Amycretin's 82% nausea rate is higher but from a smaller, earlier-phase study. Direct comparison requires larger trials.
Treatment Discontinuation#
In the Phase 1b/2a trial:
- 33% of participants discontinued overall
- 59% of discontinuations were unrelated to adverse events (withdrawal of consent, protocol violations)
- AE-related discontinuation rate was lower than the headline number suggests
In the Phase 1 oral trial:
- No deaths or serious adverse events
GLP-1 and Amylin Agonist Class Warnings#
Thyroid C-Cell Tumors#
The GLP-1 receptor agonist component carries the class-wide warning for thyroid C-cell tumors. Amycretin is expected to carry similar warnings.
Pancreatitis#
Both GLP-1 and amylin agonists have been associated with pancreatitis. Dual mechanism may warrant enhanced vigilance.
Gallbladder Disease#
The substantial weight loss (up to 24.3% at 36 weeks) increases gallstone risk.
Acute Kidney Injury#
The high rate of GI events (nausea 82%, vomiting 53%) may cause dehydration, increasing AKI risk.
Amylin-Specific Considerations#
Injection Site Reactions#
Amylin analogs can cause injection site reactions. Rates with amycretin were low and consistent with other SC peptide therapies.
Hypoglycemia in Combination with Insulin#
The amylin component suppresses glucagon and delays gastric emptying, which combined with insulin may increase hypoglycemia risk.
Heart Rate Effects#
GLP-1 agonists typically increase resting heart rate by 2-4 bpm. Heart rate effects specific to amycretin have not been separately characterized.
Special Populations#
Full safety data in renal impairment, hepatic impairment, elderly, and pediatric populations are not available from early-phase trials.
Drug Interactions#
- Insulin and sulfonylureas: Dose adjustment needed; dual mechanism increases hypoglycemia risk
- Oral medications: Additive gastric emptying delay from GLP-1 and amylin agonism may affect absorption more than single-mechanism drugs
- Oral contraceptives: Enhanced gastric delay may reduce absorption
Related Reading#
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Medical Disclaimer
This website is for educational and informational purposes only. The information provided is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare professional before using any peptide or supplement.