Comparison of Different Doses of Sodium-Glucose Ttransporter-2 Inhibitors (SGLT2i) to SGLT2i with Magnesium Infusions for Refractory Hypomagnesaemia in a Patient with Monogenic Diabetes Type-5 (MODY-5)

Introduction:

Introduction: MODY-5 is a rare autosomal dominant form of monogenic diabetes attributed to deletions of chromosome 17q12 with impaired expression of HNF1β (Hepatocyte Nuclear Factor 1 homeobox Beta. The deficient HNF1B down regulated the expression of FXYD2. Refractory hypomagnesemia is commonly observed in patients with MODY-5 due to downregulated FXYD2 which blocked the encoding of the γ (gamma) subunit of the Na+-K+-ATPase and indirectly led to hypomagnesemia. SGLT2i have been associated with small but significant increases in serum magnesium (sMg) levels in patients with diabetes. We report our patient's experience comparing the use of SGLT2i at different doses to SGLT2i with Mg infusions for refractory hypomagnesemia in a patient with MODY-5.

Case Description:
29 y/o Caucasian female with family history of young onset diabetes was diagnosed with MODY-5 at the age of 19 years old when she was found to have kidney cysts that were noted incidentally on MRI spine. She presents to our clinic with hypertension, catamenial headaches, hyperuricemia, refractory hypomagnesemia to oral magnesium supplements (400 mg twice a day) due to Mg wasting syndrome, congenital pancreatic atresia and exocrine pancreatic insufficiency. sMg levels have been <1.0mg/dl for 2 years and was symptomatic due to it such as fatigue, headaches and muscle aches. Most lately, she could not tolerate more than 1000mg twice a day of oral magnesium due to diarrhea. Prior to starting SGLT2i her sMg was <1.0 mg/dl and fractional excretion of magnesium (FEMg) was 14.5% (normal FEMg <4% in the setting of hypomagnesemia). She was started on canagliflozin 100 mg and was titrated to 300 mg; which has improved her sMg level from 0.9 mg/dl to 1.2 mg/dl and was stable with this dose for weeks. FEMg data was not available for the dose change of canagliflozin. She was also started on amiloride 5 mg daily. sMg levels have dropped to <1 md/dL when the canagliflozin has been stopped due to insurance but improved again after starting empagliflozin. On 10 mg of empagliflozin compared to 25mg of empagliflozin the sMg level has not changed and remained at 1.1 mg/dl level but the FEMg improved from 10% to 7.25%. She continued to have symptoms of hypomagnesemia, so she was started on magnesium sulfate 2 gm in 100 ml normal saline infused over 12 hrs 3 times a week for 6 months. Her symptoms improved after the infusion, but they wear off quickly. Magnesium infusions improved the sMg to 1.5 mg/dl but the FEMg was 12.6%. did not improve. Lately due to treatment burden of Magnesium infusion, they were decreased to 2 times per week.

Discussion:
SGLT2i improve refractory hypomagnesemia due to Mg wasting syndrome. Her sMg improved to >1 mg/dL with SGLT2i. There was no difference in sMg comparing low versus high doses of empagliflozin, but an improvement in FEMg. Adding magnesium infusion to SGLT2i slightly improved sMg, but at the expense of burden of the disease treatment.