The overall benefits of empagliflozin treatment in adult siblings with glycogen storage disease type Ib: one year experience

Bidiuk, Joanna; Gaciong, Zbigniew; Sobieraj, Piotr

doi:10.5114/aoms/150029

Cited by 13 publications

(19 citation statements)

References 14 publications

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“…Although not evaluated by reliable standardized tools both patients and their families reported improved quality of life following EMPA treatment. Our results are in line with previous case reports ( 13 , 14 , 18 , 19 ) and with a recent study reporting the accumulated real-life experience of 112 GSD1b patients treated with EMPA in 24 countries ( 15 ). Accordingly, neutrophil counts were improved in the majority of patients which had allowed to stop the regular GCSF injections in 55% of the patients involved in the study.…”

Section: Discussionsupporting

confidence: 93%

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Favorable outcome of empagliflozin treatment in two pediatric glycogen storage disease type 1b patients

et al. 2022

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BackgroundGlycogen storage disease type 1b (GSD1b) is an ultra-rare autosomal recessive disorder, caused by mutations in SLC37A4 gene. Affected patients present with episodes of fasting hypoglycemia and lactic acidosis, hepatomegaly, growth retardation, hyperlipidemia and renal impairment. In addition, patients present neutropenia, neutrophil dysfunction and oral, and skin infections as well as a significant predisposition to develop inflammatory bowel disease (IBD). Low neutrophil counts and function is related to the toxic accumulation of 1,5-anhydroglucitol-6-phosphate (1,5-AG6P). Recently, several reports have shown that off-label treatment with empagliflozin (EMPA), an inhibitor of the renal glucose transporter SGLT2, decreased blood 1,5-anhydroglucitol (1,5-AG), and neutrophil 1,5-AG6P, thus resulting in a new therapeutic option for neutropenia and neutrophil dysfunction in patients.MethodsOff-label treatment with EMPA was established in two GSD1b patients after signed informed consent. The patients were followed clinically. We monitored neutrophil counts and function, 1,5-AG levels in plasma and its renal clearance before and during EMPA treatment.ResultsA 17 year-old girl who had long standing oral ulcers and developed IBD, requiring systemic steroid and regular granulocyte colony-stimulating factor (GCSF) therapy and an 8 year-old boy who had steady non healing oral lesions were treated with empagliflozin during 18–24 months. Treatment led to increase of neutrophil counts and function with substantial clinical improvement. This included remission of IBD in the first patient which allowed to discontinue both GCSF and steroid therapy and resolution of oral lesions in both patients. The concentration of 1,5-AG in blood was greatly decreased within two weeks of treatment and remained stable thereafter.ConclusionsRepurposing of empagliflozin to treat neutropenia in two GSD1b patients was safe and resulted in the urinary excretion of 1,5-AG, the normalization of neutrophil function, and a remarkable improvement of neutropenia-related clinical traits. We showed for the first time that empagliflozin increases concomitantly the renal clearance of both 1,5-anhydroglucitol and glucose in GSD1b patients.

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Section: Discussionsupporting

confidence: 93%

“…Subsequently, several case reports have shown beneficial effects of EMPA treatment on neutropenia in GSD1b and G6PC3-deficient patients. This improved neutrophil counts and function resulting in clinical improvement and in some cases discontinuation of GCSF treatment (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Favorable outcome of empagliflozin treatment in two pediatric glycogen storage disease type 1b patients

et al. 2022

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“…Other case reports displayed an improved glycemic control (27, 31) or did not reveal any increased hypoglycemia (18,26,27,30).…”

Section: Empagliflozin Use In Glycogen Storage Disease Type Ibmentioning

confidence: 94%

“…The treatment with empagliflozin allowed to reduce the G-CSF dosage and the number of medications for concomitant clinical conditions. In his brother, who also suffered from HLA-B27 positive arthritis and sinus tachycardia, empagliflozin allowed corticosteroid withdrawal and antiarrhythmic therapy was tapered, without alterations in glycemic control (30).…”

Section: Evidences From Glycogen Storage Disease Type Ibmentioning

confidence: 99%

“…Data from case reports and a questionnaires from 112 patients showed that treatment with empagliflozin has significant beneficial effects on neutrophil dysfunction, mucosal lesions, recurrent infections, anemia and bowel diseases (6,18,23,24,(26)(27)(28)(29)(30)(31)(32). Furthermore, the majority of patients displayed an amelioration of glycemic control with a better fasting tolerance and metabolic parameters (6,24,27,31).…”

Section: Empagliflozin Use In Glycogen Storage Disease Type Ibmentioning

confidence: 99%

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Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders

2023

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Glycogen storage type Ib (GSDIb) is a rare inborn error of metabolism caused by glucose-6-phosphate transporter (G6PT, SLC37A4) deficiency. G6PT defect results in excessive accumulation of glycogen and fat in the liver, kidney, and intestinal mucosa and into both glycogenolysis and gluconeogenesis impairment. Clinical features include hepatomegaly, hypoglycemia, lactic acidemia, hyperuricemia, hyperlipidemia, and growth retardation. Long-term complications are liver adenoma, hepatocarcinoma, nephropathy and osteoporosis. The hallmark of GSDIb is neutropenia, with impaired neutrophil function, recurrent infections and inflammatory bowel disease. Alongside classical nutritional therapy with carbohydrates supplementation and immunological therapy with granulocyte colony-stimulating factor, the emerging role of 1,5-anhydroglucitol in the pathogenesis of neutrophil dysfunction led to repurpose empagliflozin, an inhibitor of the renal glucose transporter SGLT2: the current literature of its off-label use in GSDIb patients reports beneficial effects on neutrophil dysfunction and its clinical consequences. Surprisingly, this glucose-lowering drug ameliorated the glycemic and metabolic control in GSDIb patients. Furthermore, numerous studies from big cohorts of type 2 diabetes patients showed the efficacy of empagliflozin in reducing the cardiovascular risk, the progression of kidney disease, the NAFLD and the metabolic syndrome. Beneficial effects have also been described on peripheral neuropathy in a prediabetic rat model. Increasing evidences highlight the role of empagliflozin in regulating the cellular energy sensors SIRT1/AMPK and Akt/mTOR, which leads to improvement of mitochondrial structure and function, stimulation of autophagy, decrease of oxidative stress and suppression of inflammation. Modulation of these pathways shift the oxidative metabolism from carbohydrates to lipids oxidation and results crucial in reducing insulin levels, insulin resistance, glucotoxicity and lipotoxicity. For its pleiotropic effects, empagliflozin appears to be a good candidate for drug repurposing also in other metabolic diseases presenting with hypoglycemia, organ damage, mitochondrial dysfunction and defective autophagy.

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Patient‐reported outcomes on empagliflozin treatment in glycogen storage disease type Ib: An international questionnaire study

et al. 2023

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In patients with glycogen storage disease type Ib (GSD Ib), quality of life is severely hampered by neutropenia and neutropenia-associated symptoms. SGLT2 inhibitors are a new treatment option and have shown improved medical outcomes in more than 120 patients so far. The aim of this international questionnaire study was to assess patient-reported outcomes of this new treatment in GSD Ib patients. Patients and caregivers of pediatric patients were invited to complete a web-based questionnaire. This was designed to evaluate treatment effects of the SGLT2 inhibitor empagliflozin on clinical symptoms and important aspects of daily life including physical performance, sleep, social and work life, traveling, socioeconomic aspects, and quality of life. The questionnaire was completed by 73 respondents from 17 different countries. The mean duration of treatment was 15 months, the cumulative treatment time was 94.8 years. More than 80% of patients reported an improved quality of life. The number of hospitalizations was reduced (66% of patients), as well as the number of days absent from school or work. Granulocyte colony-stimulating factor (G-CSF) treatment could be stopped in 49% of patients and reduced in another 42%. Clear improvement of neutropenia and all neutropenia-associated symptoms was reported by the majority of patients. Additionally, patients or caregivers reported positive effects on appetite (63%), level of activity (75%), overall well-being (96%), and sleep (63%). Empagliflozin positively impacts many aspects of daily life including work and social life and thereby significantly improves quality of life of patients and caregivers. K E Y W O R D S empagliflozin, glycogen storage disease type Ib, neutropenia, quality of life, SGLT2 inhibitor Saskia B. Wortmann and Terry G. J. Derks contributed equally to this study.

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The overall benefits of empagliflozin treatment in adult siblings with glycogen storage disease type Ib: one year experience

Cited by 13 publications

References 14 publications

Favorable outcome of empagliflozin treatment in two pediatric glycogen storage disease type 1b patients

Favorable outcome of empagliflozin treatment in two pediatric glycogen storage disease type 1b patients

Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders

Patient‐reported outcomes on empagliflozin treatment in glycogen storage disease type Ib: An international questionnaire study

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