Can Glucagon-like peptide-1 receptor agonists (GLP-1s) impact a patient's singing voice?

Can GLP-1 Receptor Agonists Impact Singing Voice?

GLP-1 receptor agonists can potentially affect singing voice through multiple mechanisms, primarily via gastroesophageal reflux disease (GERD) and less commonly through direct laryngeal effects, though these are not among the most common side effects.

Primary Mechanism: GERD-Related Voice Changes

GERD represents the most clinically significant pathway by which GLP-1 receptor agonists may impact vocal quality. GLP-1 receptors on the myenteric plexus activate nitrergic pathways that inhibit vagal activity on the gut, leading to reduced phasic gastric contractions, delayed gastric emptying, and increased fasting and postprandial gastric volumes 1, 2. This delayed gastric emptying mechanism is integral to the drugs' therapeutic effects but creates conditions favorable for reflux 3, 4.

• GERD had very high signal ratios and was significant across all GLP-1 receptor agonists assessed in adverse event reporting, making it one of the most consistent otolaryngologic side effects 5
• The delayed gastric emptying persists even with long-acting formulations like semaglutide, as demonstrated by scintigraphy studies 1, 3
• Gastric distension from retained contents can increase intra-abdominal pressure, promoting reflux episodes 2

Clinical Impact on Voice

GERD-induced laryngopharyngeal reflux causes:

• Vocal fold edema and erythema from acid exposure
• Chronic throat clearing and cough
• Dysphonia (hoarseness)
• Reduced vocal range and endurance
• Increased vocal effort required for phonation

Direct Laryngeal Effects

Dysphonia was reported as a significant adverse event specifically with liraglutide, suggesting potential direct effects beyond GERD 5. The mechanism may involve:

• GLP-1 receptors are expressed in multiple organs including the central nervous system, which could theoretically affect neural control of laryngeal function 1
• Dry mouth (xerostomia) was a significant adverse event with semaglutide, which can indirectly affect vocal quality by reducing lubrication of the vocal folds 5

Additional Relevant Side Effects

• Dysgeusia (taste disturbance) was significant with semaglutide, liraglutide, and exenatide, which may affect a singer's ability to assess vocal quality 5
• Nausea and vomiting occur in 17-44% of patients and are dose-dependent, potentially causing vocal strain from repeated emesis 1

Tachyphylaxis Considerations

The effects on gastric emptying show tachyphylaxis with continuous exposure, suggesting autonomic nervous system adaptation 1. However:

• Acute and intermittent infusions have more pronounced effects on delaying gastric emptying than continuous infusion 1
• Despite tachyphylaxis to some gastric effects, patients still experience delayed emptying after the second meal 1
• Two studies using long-acting semaglutide (12-20 weeks) showed no delay in gastric emptying using paracetamol absorption tests, though this test is now considered suboptimal 1

Clinical Management Algorithm

For Singers Considering GLP-1 Receptor Agonists:

1. Pre-treatment assessment: Screen for pre-existing GERD, as this is a relative contraindication given the high risk of exacerbation 5

2. Medication selection: Consider that GERD signals were significant across all GLP-1 receptor agonists, so switching agents may not eliminate risk 5

3. Dose titration: Use slow titration starting at the lowest available dose and increasing gradually over weeks to months to minimize gastrointestinal side effects 1, 2

4. Monitoring: Assess for GERD symptoms, dysphonia, and dry mouth at each follow-up visit (every 4 weeks during titration, then every 3 months) 6

For Singers Already on GLP-1 Receptor Agonists with Voice Changes:

1. Treat GERD aggressively: Use proton pump inhibitors, H2 blockers, and lifestyle modifications (elevate head of bed, avoid late meals, dietary modifications) 2

2. Optimize hydration: Maintain at least 8 glasses of water daily to combat dry mouth and support vocal fold lubrication 2

3. Consider dose reduction: If glycemic control and weight loss goals permit, evaluate for dose reduction to minimize gastrointestinal effects 2

4. Laryngoscopy evaluation: If dysphonia persists despite GERD management, refer to otolaryngology for direct laryngeal examination to rule out other pathology 5

Critical Caveats

• Most gastrointestinal adverse events are manageable with supportive care and often improve with continued use due to tachyphylaxis, so do not discontinue therapy prematurely for mild symptoms 2
• The gastrointestinal effects are dose-dependent and occur more frequently with short-acting formulations than long-acting preparations 2, 7
• Professional voice users (singers, teachers, actors) should be specifically counseled about these risks before initiating therapy, as even mild dysphonia may significantly impact their livelihood