Abstract: FR-PO0870
Shrinking Waistline and Shrinking Sodium: GLP-1 Receptor Agonist-Induced Severe Hyponatremia
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Case Reports - 1
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Reyes-Jimenez, Carmen Johanna, Hospital General Menonita de Cayey, Cayey, Puerto Rico
- Torres-Rivera, Gabriel J., Hospital General Menonita de Cayey, Cayey, Puerto Rico
Introduction
We present a rare case of GLP-1 receptor agonist-induced severe symptomatic hyponatremia secondary to a “triple hit” mechanism.
Case Description
51-year-old man with a history of T2DM, HTN and dyslipidemia presented with somnolence, disorientation, persistent nausea, non-bilious emesis, and 7 days of oral intolerance. Medications included irbesartan (300 mg/d), chlorthalidone (25 mg/d), and amlodipine (10 mg/d). Semaglutide was started 5 weeks prior, titrated to 0.5 mg before symptom onset. At ER, he developed confusion. Nausea and vomiting persisted despite IV fluids and ondansetron. Physical exam was notable for dry mucous membranes and decreased skin turgor. Labs showed an unremarkable hemogram. Stable renal function (SCr: 0.57 mg/dL, BUN: 9 mg/dL). Normal TSH (1.76) and cortisol (13.5). Severe hyponatremia (Na 109 mmol/L), K 4.4 mmol/L, Cl 68 mmol/L, CO2 28 mmol/L, Glucose 107 mg/dL. Calculated serum osmolality: 227.15 mOsm/kg. CT abdomen/pelvis was unremarkable. Findings were consistent with severe acute hypovolemic hypotonic hyponatremia.
Given severe symptomatic hyponatremia with neurologic manifestations, the patient received 100 mL of 3% IV hypertonic saline. A 2-hour repeat Na was 111 mmol/L, with minimal neurological improvement. A second 100 mL dose was administered, with improvement in nausea and somnolence. Three days after treatment, urine osmolality was 101 mOsm/kg (admission UOsm not available). This water diuresis demonstrated the expected ADH suppression after intravascular volume restoration, ruling out true SIADH. This confirmed the diagnosis of profound hypovolemic hyponatremia associated with GLP-1-induced GI losses and thiazide diuretic use. 7 days after management, Na was corrected to 131 mmol/L, and the patient was discharged with full symptom recovery.
Discussion
GLP-1 RAs inhibit the sodium-hydrogen exchanger isoform 3 (NHE3) in the proximal tubule, reducing 60–70% of filtered Na reabsorption. Chlorthalidone inhibits the Na+–Cl– cotransporter in the distal tubule, resulting in a sequential nephron block. In addition, patient had decreased oral intake and GI losses due to GLP-1. Severe hyponatremia can cause life-threatening, refractory seizures and neurological symptoms, even in low-risk individuals. Clinicians should be aware of potential electrolyte disturbances when initiating GLP-1 receptor agonists for weight loss, especially when diuretics are used concurrently.