Cotadutide (MEDI0382): Side Effects
Known side effects, contraindications, and interactions
📌TL;DR
- •5 known side effects documented
- •3 mild, 2 moderate, 0 severe
- •3 contraindications listed
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Side Effects Severity Chart
Reported in approximately 35% of cotadutide-treated patients in the phase 2b trial. Severity decreased over time with continued dosing, consistent with GLP-1 receptor agonist class effects.
Reported in approximately 17% of patients. Generally transient and decreasing in frequency with continued treatment and dose escalation.
Reduced appetite was observed, consistent with GLP-1 receptor agonism effects on central satiety pathways. This effect contributed to the weight loss observed in clinical trials.
Gastrointestinal disturbances including diarrhea were reported at rates consistent with other GLP-1 receptor agonists.
Local reactions at the injection site were reported at rates consistent with other subcutaneous peptide therapies.
⛔Contraindications
- •Development was discontinued; not available for clinical use
- •History of medullary thyroid carcinoma or MEN2 (GLP-1 agonist class contraindication based on rodent studies)
- •Known hypersensitivity to GLP-1 receptor agonists
⚠️Drug Interactions
- •Insulin and sulfonylureas: Potential for increased hypoglycemia risk (GLP-1 agonist class effect)
- •Oral medications: Delayed gastric emptying may affect absorption of co-administered oral drugs
- •Glucagon for hypoglycemia rescue: Theoretical concern that GCGR agonism could affect glucagon rescue response
Community-Reported Side Effects
See which side effects community members report most frequently.
0View community protocolsSafety Overview#
Cotadutide's safety profile in clinical trials was characterized by gastrointestinal adverse events consistent with the GLP-1 receptor agonist class, with nausea and vomiting being the most common. The safety data were considered acceptable by AstraZeneca, and the program was not discontinued due to safety concerns.
Gastrointestinal Adverse Events#
The most common side effects in the phase 2b trial (Nahra et al., 2021) were gastrointestinal in nature:
| Adverse Event | Cotadutide (pooled) | Placebo | Liraglutide 1.8 mg |
|---|---|---|---|
| Nausea | ~35% | Low | ~20-25% |
| Vomiting | ~17% | Low | ~10% |
The GI adverse event rates were higher than liraglutide but within the range observed for GLP-1 agonists as a class. Importantly, the rates decreased over time with continued dosing, and dose escalation protocols helped mitigate initial GI intolerance.
Glucagon-Related Safety Considerations#
The glucagon receptor agonist component of cotadutide raised theoretical safety concerns that were not observed to be clinically significant:
- Hyperglycemia: The glucagon component could theoretically counteract the glucose-lowering effect of GLP-1 agonism. In practice, the GLP-1-biased selectivity of cotadutide was sufficient to produce net glycemic improvement
- Ketogenesis: Glucagon promotes hepatic ketone production. No clinically significant increases in ketones were reported
- Heart rate: Small increases in heart rate were observed, consistent with both GLP-1 and glucagon receptor activation
Comparison with Other GLP-1-Based Agents#
| Safety Parameter | Cotadutide | Semaglutide 1.0 mg | Liraglutide 1.8 mg |
|---|---|---|---|
| Nausea | ~35% | 15-20% | 20-25% |
| Vomiting | ~17% | 5-10% | 10% |
| Injection-site reactions | Mild | Mild | Mild |
| Hypoglycemia (monotherapy) | Low | Low | Low |
| Heart rate increase | Small | Small | Small |
Long-Term Safety#
Long-term safety data beyond 54 weeks were not obtained due to program discontinuation. The phase 2b trial duration of 54 weeks provided adequate data for phase 2 assessment but was insufficient for characterizing long-term safety, particularly regarding the chronic effects of glucagon receptor co-agonism.
Safety Profile Context#
Cotadutide (MEDI0382) belongs to the Metabolic category of research peptides. Understanding the side effect profile of Cotadutide (MEDI0382) is essential for researchers designing clinical protocols and for healthcare providers advising patients. The side effects documented here are based on available clinical trial data and may not represent the complete safety profile.
Reported Side Effects#
The following side effects have been documented in clinical studies of Cotadutide (MEDI0382). Side effect severity and frequency are based on available clinical data.
Nausea#
Severity: moderate | Frequency: very-common
Reported in approximately 35% of cotadutide-treated patients in the phase 2b trial. Severity decreased over time with continued dosing, consistent with GLP-1 receptor agonist class effects.
Vomiting#
Severity: moderate | Frequency: common
Reported in approximately 17% of patients. Generally transient and decreasing in frequency with continued treatment and dose escalation.
Decreased Appetite#
Severity: mild | Frequency: common
Reduced appetite was observed, consistent with GLP-1 receptor agonism effects on central satiety pathways. This effect contributed to the weight loss observed in clinical trials.
Diarrhea#
Severity: mild | Frequency: common
Gastrointestinal disturbances including diarrhea were reported at rates consistent with other GLP-1 receptor agonists.
Injection-Site Reactions#
Severity: mild | Frequency: common
Local reactions at the injection site were reported at rates consistent with other subcutaneous peptide therapies.
Contraindications#
The following contraindications have been identified for Cotadutide (MEDI0382) based on available research and pharmacological considerations:
- Development was discontinued; not available for clinical use
- History of medullary thyroid carcinoma or MEN2 (GLP-1 agonist class contraindication based on rodent studies)
- Known hypersensitivity to GLP-1 receptor agonists
Individuals with any of these conditions should not use Cotadutide (MEDI0382) without consulting a qualified healthcare provider.
Drug Interactions#
The following potential drug interactions have been identified for Cotadutide (MEDI0382):
- Insulin and sulfonylureas: Potential for increased hypoglycemia risk (GLP-1 agonist class effect)
- Oral medications: Delayed gastric emptying may affect absorption of co-administered oral drugs
- Glucagon for hypoglycemia rescue: Theoretical concern that GCGR agonism could affect glucagon rescue response
Drug interaction studies for Cotadutide (MEDI0382) remain limited. Researchers should exercise caution when combining Cotadutide (MEDI0382) with other compounds and consult relevant pharmacological references.
Related Reading#
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