Use of a Sodium-Glucose Cotransporter 2 Inhibitor, Empagliflozin, in a Patient with Rabson-Mendenhall Syndrome

Abstract

Introduction: Among the insulin resistance syndromes that lead to diabetes mellitus in young people, Rabson-Mendenhall syndrome (RMS; OMIM # 262190) is an autosomal recessive inherited disease caused by an insulin receptor mutation (INSR; 147,670). Due to the rarity and complexity of the disease, we have few therapeutic alternatives other than insulin with clinical studies with robust evidence. Some reports suggest the adjunct use of metreleptin, metformin, and pioglitazone with improved glycemic control, however, with results still unsatisfactory for the desirable glycemic targets for this age group. Case Presentation: We report a case of an 11-year-old patient who was diagnosed with RMS at 6 years of age, confirmed through genetic sequencing, with unsatisfactory glycemic control despite the use of >5 IU/kg/day of insulin, pioglitazone, and metformin. To optimize therapy, we used empagliflozin (SGLT2i) to correct hyperglycemia. With the use of the drug, we obtained a decrease of almost 3% in the value of glycated hemoglobin (HbA1c) and about 30% reduction in the total daily dose of insulin. Discussion/Conclusion: In this specific case, considering the glycosuric effects independent of the functionality of insulin receptors (which in this case had partial activity due to the INSR gene mutation), an improvement in glycemic control was obtained, with optimization of HbA1c without documented or reported adverse effects. From this isolated case and understanding the pharmacokinetics of this drug class, the question remains whether it would be possible to use this treatment in other situations of SIR where we also have few therapeutic perspectives.

A Novel Mutation in the INSR Gene Causes Severe Insulin Resistance and Rabson–Mendenhall Syndrome in a Paraguayan Patient

“…However, postprandial glucose surged to 11–22 mmol/L. Therefore, the patient initiated metformin treatment in 2018 with an initial dosage of 100 mg thrice daily; the treatment was discontinued for some time due to the early age of the patient [ 9 , 17 , 23 ].…”

“…Further adjustments in insulin dosages or consideration of additional therapeutic modalities may be warranted to address persistent postprandial hyperglycemia. Additionally, the recurrent nature of glycemic fluctuations underscores the importance of continuous patient education and engagement to enhance adherence to treatment plans [ 17 , 23 ]. The nephrocalcinosis observed in this case is a known complication of RMS and reflects the underlying metabolic disruption [ 16 ].…”

Frequency and characteristics of diabetes in lipodystrophies and insulin receptoropathies compared with type 1 and type 2: results from the multicenter DPV registry

“…In contrast to other types of diabetes, a significant number of patients with inborn defects of insulin signaling have been treated with SGLT2 inhibitors. This approach has been described in several case reports as a successful therapeutic approach in this disorder, as the glucosuric effect leads to an insulin receptor-independent lowering of blood glucose ( 25 , 26 , 27 , 28 ). In addition, SGLT2 inhibitors may be beneficial in this indication due to their positive effect on blood pressure ( 29 , 30 ).…”

INSR novel mutations identified in a Chinese family with severe INSR-related insulin resistance syndromes: A case report

“…With the informed consent of the patient families, recombinant human methionyl leptin (metreleptin) can reduce BMI in SDS and improve glycemic control in patients with MRS. [19,20] Evidence also suggests that sodium-glucose cotransporter 2 inhibitors (both dapagliflozin and empagliflozin) are well tolerated in patients with RMS, improving glycemic control without significantly increasing ketonemia; however, renal calcium excretion should be monitored regularly during the dosing phase. [21,22] The treatment of SIR is challenging, and the therapeutic effect of these drugs appears to diminish over time; therefore, more clinical experience is needed to guide treatment.…”