Long‐term efficacy of the sodium–glucose cotransporter 2 inhibitor, ipragliflozin, in a case of type A insulin resistance syndrome

Abstract

Type A insulin resistance (IR) syndrome is a severe IR form caused by insulin receptor (INSR) gene defects. Antidiabetic drugs, including high‐dose insulin and insulin‐sensitizing agents, often fail to control associated hyperglycemia. Therapy with recombinant human insulin‐like growth factor 1 can be more effective, but it is expensive. We report a case of type A IR syndrome with an in‐frame INSR heterozygous deletion (ΔLeu999) that was treated with a combination of conventional therapy and ipragliflozin, a sodium–glucose cotransporter 2 inhibitor. Treatment reduced hemoglobin A1c levels (10.0–7.5%) and induced weight loss (54.4–52.0 kg) within 2 months, and the effects were sustained for >3 years. Sodium–glucose cotransporter 2 inhibitors might be useful to normalize blood glucose in type A IR syndrome by reducing bodyweight and ameliorating glucotoxicity.

Combination Therapy With Semaglutide and Dapagliflozin as an Effective Approach for the Management of Type A Insulin Resistance Syndrome: A Case Report

“…in a case of extreme IR (Rabson-Mendenhall syndrome) ( 8 ). Previous studies have also reported promising results with regard to several SGLT2is, such as ipragliflozin and dapaliflozin, in the treatment of diabetes in patients with type A IR syndrome ( 9 , 10 ). Accordingly, Nagashima et al.…”

“…Accordingly, Nagashima et al. showed that the administration of ipragliflozin led to significant reductions in HbA1c (10% to 7.2%, maintained at approximately 8% for more than 3 years) in a patient with type A IR syndrome treated with metformin and high doses of insulin ( 9 ). Similarly, Hamaguchi and colleagues reported that dapagliflozin reduced HbA1c from 7.5% to 6.5% and decreased total daily dose of insulin in a case of severe IR due to a PIK3R1 mutation treated with metformin and insulin ( 10 ).…”

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 ).…”

New classification and diagnostic criteria for insulin resistance syndrome

“…Given that metformin and sodium-glucose cotransporter-2 (SGLT-2) inhibitors exert hypoglycemic actions by mechanisms independent of insulin receptor signaling, these drugs are effective in individuals with genetic insulin resistance syndrome. Case reports have thus shown that both metformin and SGLT-2 inhibitors improve glycemic control and allow insulin dose reduction in individuals with this syndrome [29,30]. In addition to insulin, insulin-like growth factor-1 (IGF-1) is administered to treat Donohue syndrome and Rabson-Mendenhall syndrome [31], although maintenance of good glycemic control in patients with these conditions remains a challenge.…”