Semaglutide promising alternative treatment for chronic myopathy of hyperkalemic periodic paralysis: a case report

Hyperkalemic Periodic Paralysis (HyperPP) is a rare autosomal dominant channelopathy characterized by episodic muscle weakness or paralysis, often triggered by elevated extracellular potassium levels. This condition is frequently linked to mutations in the SCN4A gene, encoding a skeletal muscle sodium channel. Traditional management strategies, such as potassium avoidance, low-potassium diets, and carbonic anhydrase inhibitors like acetazolamide and diclofenamide, have provided limited long-term relief, particularly in addressing the progressive myopathy associated with the disease.

Case Report

A 48-year-old male with a confirmed SCN4A mutation (Threonine to Methionine at position 704) presented with longstanding muscle weakness. Symptom onset occurred in childhood, with progressive deterioration into permanent weakness by his thirties. Conventional therapies were ineffective. In 2023, the patient began weekly semaglutide injections for weight loss. Remarkable improvement in muscle strength and mobility was noted within a year, with the patient regaining the ability to rise unaided from a chair and walk at a normal pace. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is primarily indicated for type 2 diabetes and obesity. However, this case suggests its potential in neuromuscular disorders. GLP-1 RAs may exert anabolic effects on skeletal muscle through insulin-dependent and insulin-independent pathways, improving mitochondrial function, glucose uptake, and reducing inflammation—factors potentially beneficial in muscle channelopathies This case provides preliminary evidence that semaglutide may reverse chronic myopathy in HyperPP patients. Larger studies are needed to evaluate its therapeutic potential, safety, and mechanisms in muscular channelopathies.

Brand, K., Landry, D., Mulhern, J. et al. Semaglutide reverses the chronic myopathy of hyperkalemic periodic paralysis: a case report. BMC Nephrol 26, 179 (2025). https://doi.org/10.1186/s12882-025-04068-5

Keywords:

Hyperkalemic periodic paralysis, SCN4A mutation, Semaglutide, Myopathy, GLP-1 receptor agonist, Skeletal muscle, Channelopathy, Case report