Can Vibegron Elevate Triglycerides?
Yes, vibegron can elevate triglycerides through its β3-adrenergic receptor agonist mechanism, which increases circulating glycerol and fatty acid levels by promoting lipolysis. 1
Mechanism of Triglyceride Elevation
Vibegron is a potent and selective β3-adrenergic receptor agonist that acts on adipose tissue to promote lipolysis. 2, 1 In preclinical studies, vibegron administration caused dose-dependent increases in circulating glycerol and fatty acid levels in both rhesus monkeys and rats, suggesting these circulating lipids serve as surrogate biomarkers of β3-adrenergic receptor activation. 1 This mechanism is inherent to the drug class and represents on-target pharmacological activity rather than an off-target adverse effect.
Clinical Significance and Monitoring
The clinical translation of these preclinical lipid elevations to human patients remains to be fully determined. 1 However, given that β3-adrenergic receptor activation fundamentally increases lipolysis and circulating free fatty acids, clinicians should be aware of this potential metabolic effect when prescribing vibegron.
For patients with pre-existing hypertriglyceridemia (triglycerides ≥150 mg/dL), baseline and periodic monitoring of lipid panels is prudent, particularly in those with:
- Severe hypertriglyceridemia (≥500 mg/dL), where further elevation could increase pancreatitis risk 3, 4
- Diabetes mellitus with poor glycemic control 4
- Metabolic syndrome 3
- Concurrent use of other medications that raise triglycerides (atypical antipsychotics, beta-blockers, thiazides, estrogens) 3, 5, 6
Clinical Trial Safety Profile
In the pivotal phase 3 trial of 1,232 patients treated with vibegron 50-100 mg daily for 12 weeks, drug-related adverse events occurred in only 5.4-7.6% of patients, similar to placebo (5.1%). 7 A systematic review of three high-quality randomized controlled trials involving 2,120 patients confirmed vibegron was well-tolerated with a favorable safety profile. 8 However, these trials did not specifically report lipid parameters as safety outcomes, so the clinical magnitude of triglyceride elevation in humans remains incompletely characterized.
Practical Recommendations
Obtain baseline fasting lipid panel before initiating vibegron in patients with:
- Known dyslipidemia 3, 4
- Diabetes mellitus 4
- Metabolic syndrome 3
- Family history of severe hypertriglyceridemia or pancreatitis 6
Recheck lipids at 3 months after initiation if baseline triglycerides are 150-499 mg/dL. 4 If triglycerides increase to ≥500 mg/dL, immediately initiate fibrate therapy to prevent acute pancreatitis while reassessing the need for continued vibegron therapy. 3, 4
The real-world adherence data showing median persistence of only 142 days suggests most patients discontinue vibegron within 5 months, 9 which may limit the duration of lipid exposure in clinical practice.