Two Cases of Thyrotoxicosis and Euglycemic Diabetic Ketoacidosis Under Sodium-glucose Transport Protein 2 Inhibitor Treatment

Hitsuwari, Takuhei; Tsurutani, Yuya; Yamane, Takahiro; Sunouchi, Takashi; Horikoshi, Hirofumi; Hirose, Rei; Hoshino, Yoshitomo; Watanabe, Satoshi; Katsuragawa, Sho; Saitou, Jun

doi:10.2169/internalmedicine.8830-21

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…We are highly concerned about a rare case report. According to a case report from 2022, one patient exhibited symptoms of thyrotoxicosis during the treatment of type 2 diabetes with SGLT-2 inhibitors (13). Due to the rarity of such cases, we cannot determine whether SGLT-2 inhibitors affect thyroid function.…”

Section: Discussionmentioning

confidence: 99%

“…However, there is presently a lack of research exploring the potential connection between SGLT-2 inhibitors and thyroid dysfunction, highlighting the signi cance of this matter. Notably, a case report documents the manifestation of thyrotoxicosis symptoms in one patient undergoing treatment with SGLT-2 inhibitors for type 2 diabetes (13). Regrettably, this unique case report appears to have received limited attention, possibly due to the rarity of the phenomenon and the limited number of related studies available.…”

Section: Introductionmentioning

confidence: 99%

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Association of SGLT-2 Inhibitors with Thyroid Dysfunction: A Drug-Target Mendelian Randomization Study

Fu,

Liu,

Liu

et al. 2023

Preprint

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Context: Diabetes and thyroid dysfunction are prevalent endocrine disorders. Diabetes substantially increases the incidence of thyroid dysfunction, and the concurrent presence of diabetes and thyroid dysfunction further heightens the risk of adverse events associated with diabetes. However, no studies have been conducted to investigate the impact of novel antidiabetic medications, particularly sodium-glucose co-transporter 2 (SGLT-2) inhibitors, on thyroid dysfunction. Objective: This study aims to estimate the causal associations of SGLT-2 inhibitors with thyroid dysfunction. Methods: We extracted single-nucleotide polymorphisms associated with SLC5A2 gene expression and glycated hemoglobin A1c levels from a genome-wide association study predominantly conducted in individuals of European descent. These genetic variants were utilized as tools to simulate the effects of SGLT-2 inhibitors. Subsequently, we conducted drug-targeted mendelian randomization (MR) studies to assess the impact of SGLT-2 inhibitors on thyroid dysfunction and captured the results demonstrating this effect. Results:The inverse variance-weighted method served as the primary analysis technique in the MR study. Treatment with SGLT-2 inhibitors, predicted through genetic analysis, is strongly linked to a higher risk of thyroid disease (OR: 4.63, 95%CI: 2.94-7.28, p=3.23E-11), especially hypothyroidism (OR: 8.99, 95%CI: 5.31-15.25, p=3.46E-16). Furthermore, SGLT-2 inhibitors treatment substantially raises the occurrence of hyperthyroidism (OR: 1.01, 95%CI: 1-1.03, p=0.02). Conversely, immune dysfunction plays a significant role in the development of both hyperthyroidism and hypothyroidism, and SGLT-2 inhibitors treatment significantly increases the incidence of these related diseases (OR: 3.94, 95%CI: 2.74-5.67, p=1.63E-13). Conclusions: Our study found that the use of SGLT-2 inhibitors significantly increases the incidence of thyroid dysfunction.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of SGLT-2 Inhibitors with Thyroid Dysfunction: A Drug-Target Mendelian Randomization Study

Fu,

Liu,

Liu

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…Cessation of insulin and reduction of insulin dose and cessation of insulin secretagogues such sulfonyl urea can be the cause of the SGLT2i-associated euglycemic DKA [3,4]. In situations where anti-insulin hormones such as catecholamines are increased due to stress such as surgery or acute illness and insulin demand is increased, SGLT2i induces euglycemic DKA [3,4,7,8].…”

Section: To the Editormentioning

confidence: 99%

The Safety of Sodium Glucose Cotransporter 2 Inhibitors for the Elderly Diabetic Patients

Yanai,

Adachi,

Hakoshima

et al. 2023

J Endocrinol Metab

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“…Sodium-glucose cotransporter protein 2 inhibitors (SGLT2-I) are oral anti-diabetic medications that lower blood sugar by lessening the kidney’s proximal convoluted tubules’ renal glucose reuptake [ 27 ]. Within the past few years, many studies researched the cardioprotective role of SGLT2 inhibitors, such as empagliflozin, dapagliflozin, and canagliflozin, in heart failure [ 53 , 80 ].…”

Section: Introductionmentioning

confidence: 99%

SGLT2 inhibitor as a potential therapeutic approach in hyperthyroidism-induced cardiopulmonary injury in rats

Bastawy,

El-Mosallamy,

Aljuaydi

et al. 2024

Pflugers Arch - Eur J Physiol

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Hyperthyroidism-induced cardiac disease is an evolving health, economic, and social problem affecting well-being. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2-I) have been proven to be cardio-protective when administered in cases of heart failure. This study intended to investigate the potential therapeutic effect of SGLT2-I on hyperthyroidism-related cardiopulmonary injury, targeting the possible underlying mechanisms. The impact of the SGLT2-I, dapagliflozin (DAPA), (1 mg/kg/day, p.o) on LT4 (0.3 mg/kg/day, i.p)-induced cardiopulmonary injury was investigated in rats. The body weight, ECG, and serum hormones were evaluated. Also, redox balance, DNA fragmentation, inflammatory cytokines, and PCR quantification in heart and lung tissues were employed to investigate the effect of DAPA in experimentally induced hyperthyroid rats along with histological and immunohistochemical examination. Coadministration of DAPA with LT4 effectively restored all serum biomarkers to nearly average levels, improved ECG findings, and reinstated the redox balance. Also, DAPA could improve DNA fragmentation, elevate mtTFA, and lessen TNF-α and IGF-1 gene expression in both organs of treated animals. Furthermore, DAPA markedly improved the necro-inflammatory and fibrotic cardiopulmonary histological alterations and reduced the tissue immunohistochemical expression of TNF-α and caspase-3. Although further clinical and deep molecular studies are required before transposing to humans, our study emphasized DAPA’s potential to relieve hyperthyroidism-induced cardiopulmonary injury in rats through its antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as via antagonizing the sympathetic over activity.

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Two Cases of Thyrotoxicosis and Euglycemic Diabetic Ketoacidosis Under Sodium-glucose Transport Protein 2 Inhibitor Treatment

Cited by 6 publications

References 39 publications

Association of SGLT-2 Inhibitors with Thyroid Dysfunction: A Drug-Target Mendelian Randomization Study

Association of SGLT-2 Inhibitors with Thyroid Dysfunction: A Drug-Target Mendelian Randomization Study

The Safety of Sodium Glucose Cotransporter 2 Inhibitors for the Elderly Diabetic Patients

SGLT2 inhibitor as a potential therapeutic approach in hyperthyroidism-induced cardiopulmonary injury in rats

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