SGLT2 inhibitors for genetic and acquired insulin resistance: Considerations for clinical use

Hosokawa, Yusei; Ogawa, Wataru

doi:10.1111/jdi.13309

Cited by 15 publications

(11 citation statements)

References 16 publications

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“…Recently, a trial showed benefits of long‐term treatment with metreleptin in persons with Rabson‐Mendenhall Syndrome 236 . Use of SGLT2i has also been reported to be beneficial in improving hyperglycemia 237,238 . For females, the hirsutism resulting from ovarian hyperandrogenism should be managed using similar strategies as for polycystic ovarian syndrome 239 …”

Section: Monogenic Insulin Resistance Syndromesmentioning

confidence: 99%

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ISPAD Clinical Practice Consensus Guidelines 2022: The diagnosis and management of monogenic diabetes in children and adolescents

et al. 2022

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Section: Monogenic Insulin Resistance Syndromesmentioning

confidence: 99%

“… 236 Use of SGLT2i has also been reported to be beneficial in improving hyperglycemia. 237 , 238 For females, the hirsutism resulting from ovarian hyperandrogenism should be managed using similar strategies as for polycystic ovarian syndrome. 239 …”

Section: Monogenic Insulin Resistance Syndromesmentioning

confidence: 99%

ISPAD Clinical Practice Consensus Guidelines 2022: The diagnosis and management of monogenic diabetes in children and adolescents

et al. 2022

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“…His plasma blood ketone bodies had a variation of 0.1–0.7 mmol/L, but it was still far from the impending ketoacidosis limit (1.6–3.0 mmol/L) [6] during the treatment [6]. Previous reports of treatment with SGLT2 inhibitors in patients with severe insulin resistance syndromes were in cases of generalized lipodystrophy, SHORT syndrome, and type A insulin resistance syndrome [7, 8]. SGLT2 inhibitors, acting through an insulin-independent manner, are effective and safe in individuals with type 2 diabetes, and the report presented here demonstrated their effectiveness in a patient with RMS.…”

Section: Discussion/conclusionmentioning

confidence: 99%

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

Santos¹,

Ramaldes²,

Gabbay³

et al. 2021

Horm Res Paediatr

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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.

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“…Among these drugs, sodium-glucose transporter 2 (SGLT2) inhibitors have gained the stage because of their renoprotective effects [ 58 ], which are related to lowering of the intraglomerular pressure by modulation of pre- and post-glomerular vascular tone [ 59 ]. SGLT2 inhibitors lower blood glucose by increasing urinary glucose excretion with a mechanism that is apparently independent of insulin action [ 60 ]. While some studies have reported that surrogate indexes of insulin resistance such as the homeostasis model assessment (HOMA) and the Matsuda Index were improved by treatment of type 2 diabetes with SGLT2 inhibitors [ 60 ], studies conducted with the use of the hyperinsulinemic-euglycemic clamp provided controversial results [ 61 , 62 ].…”

Section: Insulin and The Kidneymentioning

confidence: 99%

“…SGLT2 inhibitors lower blood glucose by increasing urinary glucose excretion with a mechanism that is apparently independent of insulin action [ 60 ]. While some studies have reported that surrogate indexes of insulin resistance such as the homeostasis model assessment (HOMA) and the Matsuda Index were improved by treatment of type 2 diabetes with SGLT2 inhibitors [ 60 ], studies conducted with the use of the hyperinsulinemic-euglycemic clamp provided controversial results [ 61 , 62 ]. To date, only a few studies have specifically investigated the effects of SGLT2 inhibitors on renal responsiveness to insulin.…”

Section: Insulin and The Kidneymentioning

confidence: 99%

Insulin Resistance and High Blood Pressure: Mechanistic Insight on the Role of the Kidney

et al. 2022

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The metabolic effects of insulin predominate in skeletal muscle, fat, and liver where the hormone binds to its receptor, thereby priming a series of cell-specific and biochemically diverse intracellular mechanisms. In the presence of a good secretory reserve in the pancreatic islets, a decrease in insulin sensitivity in the metabolic target tissues leads to compensatory hyperinsulinemia. A large body of evidence obtained in clinical and experimental studies indicates that insulin resistance and the related hyperinsulinemia are causally involved in some forms of arterial hypertension. Much of this involvement can be ascribed to the impact of insulin on renal sodium transport, although additional mechanisms might be involved. Solid evidence indicates that insulin causes sodium and water retention, and both endogenous and exogenous hyperinsulinemia have been correlated to increased blood pressure. Although important information was gathered on the cellular mechanisms that are triggered by insulin in metabolic tissues and on their abnormalities, knowledge of the insulin-related mechanisms possibly involved in blood pressure regulation is limited. In this review, we summarize the current understanding of the cellular mechanisms that are involved in the pro-hypertensive actions of insulin, focusing on the contribution of insulin to the renal regulation of sodium balance and body fluids.

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SGLT2 inhibitors for genetic and acquired insulin resistance: Considerations for clinical use

Cited by 15 publications

References 16 publications

ISPAD Clinical Practice Consensus Guidelines 2022: The diagnosis and management of monogenic diabetes in children and adolescents

ISPAD Clinical Practice Consensus Guidelines 2022: The diagnosis and management of monogenic diabetes in children and adolescents

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

Insulin Resistance and High Blood Pressure: Mechanistic Insight on the Role of the Kidney

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