Orforglipron Side Effects: What You Need to Know

Orforglipron, a once-daily oral GLP-1 receptor agonist developed by Eli Lilly, is gaining attention as a promising treatment for type 2 diabetes and obesity-related weight management. As with any medication, understanding the potential side effects is crucial before starting therapy.

Orforglipron Common Side Effects

Orforglipron’s side effects are similar to other drugs in the GLP-1 class, mainly gastrointestinal in nature:

• Nausea:
  Most commonly reported side effect, seen in 13–58% of participants depending on dosage.
• Diarrhea:
  Affects approximately 19–26% of users, particularly during dose escalation.
• Vomiting:
  Occurs in 5–14% of users, again dose-dependent.
• Constipation:
  Occurs more frequently than in the placebo group.
• Eructation (burping):
  Mild but noted more often than in control groups.

Discontinuation Rate

Due to adverse effects, around 10–17% of patients in clinical trials discontinued treatment with orforglipron. Most discontinuations were related to gastrointestinal discomfort during early phases of therapy.

No Major Safety Concerns Observed

Notably, no increased incidence of the following was observed in trials:

• Pancreatitis
• Liver injury
• Thyroid tumors (unlike some other GLP-1 drugs)

This gives orforglipron a favorable safety profile thus far compared to injectable GLP-1 agonists like semaglutide (Ozempic/Wegovy) and tirzepatide (Zepbound/Mounjaro).

Convenience Factor

Unlike many GLP-1-based medications that require subcutaneous injection, orforglipron is taken orally once a day, without food or timing restrictions — a huge plus for patient compliance.