Can semaglutide (glucagon-like peptide-1 receptor agonist) cause hyponatremia (low sodium levels)?

Semaglutide and Hyponatremia: Clinical Evidence and Recommendations

Based on current clinical guidelines and available evidence, semaglutide does not appear to cause hyponatremia as a recognized adverse effect.

Documented Side Effects of Semaglutide

Semaglutide, a GLP-1 receptor agonist, has well-documented side effects that do not include hyponatremia. According to clinical guidelines, the most common adverse effects include:

• Gastrointestinal effects: nausea, vomiting, and diarrhea (occurring in 15-20% of patients) 1
• Transient nausea and vomiting that are typically self-limited with longer-acting GLP-1 RAs 1
• Potential delay in gastric emptying, which may affect absorption of concomitantly administered medications 1
• Increased heart rate (typically by ~5 bpm) 1
• Risk of diabetic retinopathy complications, particularly with semaglutide in patients with prior history of proliferative retinopathy 1

Safety Profile in Renal Impairment

Semaglutide has been studied extensively in patients with various degrees of renal impairment:

• It can be used with caution in patients with severe renal impairment or end-stage renal disease (ESRD) 1
• Clinical trials have included participants with eGFR as low as 15 ml/min/1.73 m² 1
• Pharmacokinetic studies show that when adjusted for differences in sex, age, and body weight, semaglutide exposure is similar between subjects with renal impairment and those with normal renal function 2
• Hemodialysis does not appear to affect the pharmacokinetics of semaglutide 2

Contraindications and Cautions

The American College of Cardiology guidelines list specific contraindications for GLP-1 RAs, including:

• History of serious hypersensitivity reaction to the drug
• Personal or family history of medullary thyroid cancer
• Multiple endocrine neoplasia syndrome type 2 (MEN2) 1

None of these contraindications or cautions mention hyponatremia or electrolyte disturbances.

Renal Benefits of Semaglutide

Rather than causing electrolyte disturbances, semaglutide has demonstrated renal benefits:

• GLP-1 receptor agonists reduce albuminuria and slow eGFR decline 1
• Semaglutide reduced the risk of major kidney disease events by 24% compared to placebo in patients with type 2 diabetes and chronic kidney disease 3
• The mean annual eGFR slope was less steep by 1.16 ml per minute per 1.73 m² in the semaglutide group compared to placebo 3

Monitoring Recommendations

When prescribing semaglutide, guidelines recommend:

1. Monitoring for common side effects like nausea and vomiting
2. Starting with the lowest dose and up-titrating gradually to minimize gastrointestinal side effects 1
3. Having a recent eye examination prior to semaglutide initiation, especially in patients with history of retinopathy 1
4. Monitoring for hypoglycemia if used with insulin or insulin secretagogues 1

There are no specific recommendations for monitoring sodium levels or watching for hyponatremia in patients taking semaglutide.

Clinical Implications

When considering semaglutide for patients:

• It is appropriate for patients with renal impairment, with demonstrated safety down to eGFR of 15 ml/min/1.73 m² 1, 4
• It offers cardiovascular and renal protection benefits beyond glycemic control 3
• The risk of serious adverse events is actually lower with semaglutide compared to placebo (49.6% vs. 53.8%) 3

Conclusion

Hyponatremia is not listed as a known adverse effect of semaglutide in any of the major clinical guidelines or research studies. The medication has been extensively studied in populations at risk for electrolyte disturbances (such as those with renal impairment) without identification of hyponatremia as a safety concern. Clinicians should focus on monitoring for the well-established side effects of semaglutide, particularly gastrointestinal symptoms and potential retinopathy complications.