SEVERE HYPOMAGNESEMIA IN A DIABETIC PATIENT ON MULTIPLE LONG-TERM MEDICATIONS

Hypomagnesemia is a common electrolyte disorder in patients with diabetes mellitus, caused not only by diabetes-related metabolic factors but also by long-term use of certain medications. Acid-suppressive agents and antidiabetic drugs such as metformin and GLP-1 receptor agonists may impair magnesium absorption or reduce intake. We report a diabetic patient receiving multiple chronic medications who developed severe hypomagnesemia and secondary hypocalcemia.

A 53-year-old woman with a 13-year history of type 2 diabetes had been treated with metformin (1,000 mg/day) and insulin since year X–7, and vonoprazan was initiated concurrently for reflux esophagitis. In year X–4, semaglutide was added for weight control, resulting in effective weight loss but appetite loss. The dose was decreased in March of year X–1, improving appetite but leading to weight regain; thus, the dose was increased again in November of the same year. In July of year X, the metformin dose was increased from 1,000 mg to 1,500 mg/day, and she subsequently developed recurrent appetite loss. In October of year X, she presented with bilateral arm numbness and generalized fatigue. Laboratory data on admission were as follows: Na 145 mEq/L, K 3.2 mEq/L, Cl 101 mEq/L, P 4.7 mg/dL, albumin 4.5 g/dL, BUN 8.6 mg/dL, creatinine 0.54 mg/dL, urinary protein/creatinine ratio 0.08 g/gCr, intact-PTH 26 pg/mL, and 25(OH)-vitamin D 13.6 ng/mL. Serum magnesium and calcium were markedly decreased (Mg 0.4 mg/dL, Ca 6.7 mg/dL), and QT prolongation was observed on ECG. Fractional excretion of magnesium (FEMg 0.15%) and calcium (FECa < 0.1%) excluded renal magnesium wasting. She was emergently admitted to our nephrology department. Vonoprazan, metformin, and semaglutide were discontinued, and intravenous magnesium and calcium supplementation was initiated with concomitant oral alfacalcidol. Serum magnesium and calcium normalized rapidly, with resolution of QT prolongation, neurological symptoms, and appetite loss. Supplementation was tapered, and maintenance was achieved with oral magnesium oxide and alfacalcidol. Vonoprazan was replaced with famotidine. Metformin and semaglutide were not resumed, and no recurrence of hypomagnesemia or hypocalcemia was observed during follow-up.

This case highlights that severe hypomagnesemia can occur in diabetic patients receiving multiple long-term medications. Chronic acid-suppressive therapy, particularly with PPIs, has been associated with hypomagnesemia after a median duration of approximately 5.5 years. The mechanism involves elevated intestinal pH, which reduces TRPM6 channel activity and thereby decreases magnesium absorption. Although reports of P-CAB–induced hypomagnesemia remain limited, a similar pathophysiologic mechanism to that of PPIs is suspected. Long-term metformin therapy may contribute to magnesium depletion by downregulating TRPM6 expression and function, while GLP-1 receptor agonists can exacerbate magnesium deficiency through appetite suppression and decreased intake. In this patient, prolonged exposure to vonoprazan and metformin, together with reduced dietary intake associated with both metformin and GLP-1 receptor agonist dose escalation, likely acted synergistically to impair intestinal magnesium absorption. The resultant hypomagnesemia led to hypocalcemia through suppressed parathyroid hormone secretion and reduced peripheral responsiveness to PTH. Following withdrawal of the causative drugs and magnesium repletion, both magnesium and calcium levels normalized promptly and remained stable thereafter.

In diabetic patients on long-term polypharmacy, clinicians should be alert to drug-induced hypomagnesemia. Regular and long-term monitoring of serum magnesium is essential, particularly in those receiving medications that may alter intestinal absorption or hormonal regulation of magnesium homeostasis.