Flozins, inhibitors of type 2 renal sodium-glucose co-transporter – not only antihyperglycemic drugs

Abstract The kidneys play a crucial role in the regulation of the carbohydrate metabolism. In normal physiological conditions, the glucose that filters through the renal glomeruli is subsequently nearly totally reabsorbed in the proximal renal tubules. Two transporters are engaged in this process: sodium-glucose co-transporter type 1 (SGLT1), and sodium-glucose co-transporter type type 2 (SGLT2) - this being located in the luminal membrane of the renal tubular epithelial cells. It was found that the administration of dapagliflozin, a selective SGLT2 inhibitor, in patients with type 2 diabetes, is associated with the reduction of HbA1c concentration by 0.45-1.11%. Additional benefits from the treatment with dapagliflozin are the reduction of arterial blood pressure and a permanent reduction of body weight. This outcome is related to the effect of osmotic diuresis and to the considerable loss of the glucose load by way of urine excretion. Dapagliflozin may be successfully applied in type 2 diabetes monotherapy, as well as in combined therapy (including insulin), where it is equally effective as other oral anti-diabetic drugs. Of note: serious adverse effects of dapagliflozin administration are rarely observed. What is more, episodes of severe hypoglycaemia related with the treatment occur only sporadically, most often in the course of diabetes polytherapy. The most frequent effects of the SGLT2 inhibitors are inseparably associated with the mechanism of their action (the glucuretic effect), and cover urogenital infections with a mild clinical course. At present, clinical trials are being continued of the administration of several subsequent drugs from this group, the most advanced of these being the use of canagliflozin and empagliflozin.

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High sucrose diet induces morphological, structural and functional impairments in the renal tubules of Drosophila melanogaster: A model for studying type-2 diabetes mediated renal tubular dysfunction

Insect Biochemistry and Molecular Biology ◽

10.1016/j.ibmb.2020.103441 ◽

2020 ◽

Vol 125 ◽

pp. 103441

Author(s):

Lavi Rani ◽

Sanjay Saini ◽

Neha Shukla ◽

Debapratim Kar Chowdhuri ◽

Naveen Kumar Gautam

Keyword(s):

Type 2 Diabetes ◽

Tubular Dysfunction ◽

Renal Tubular Dysfunction ◽

Renal Tubules ◽

Functional Impairments ◽

Sucrose Diet ◽

High Sucrose Diet ◽

Renal Tubular ◽

High Sucrose

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Case Reports That Illustrate the Efficacy of SGLT2 Inhibitors in the Type 1 Diabetic Patient

Case Reports in Endocrinology ◽

10.1155/2015/676191 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

David S. H. Bell

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Case Reports ◽

Sglt2 Inhibitor ◽

Sglt2 Inhibitors ◽

Endogenous Insulin ◽

Large Randomized Clinical Trial ◽

Endogenous Insulin Production

SGLT2 inhibitors are only approved for use in adults with type 2 diabetes. However, because SGLT2 inhibitors have a mechanism of action that does not require the presence of endogenous insulin, these drugs should also be efficacious in type 1 diabetes where endogenous insulin production is greatly reduced or absent. Herein, I present five cases which illustrate the benefits of utilizing an SGLT2 inhibitor with type 1 diabetes. In these cases the use of SGLT2 inhibitors resulted not only in better glycemic control in most patients but also in some patients’ less hypoglycemia, weight loss, and decreased doses of insulin. In type 1 diabetesCandida albicansvaginitis and balanitis may occur more frequently than in type 2 diabetes. These cases show that a large randomized clinical trial of SGLT2 inhibitors in type 1 diabetes needs to be performed.

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Euglycemic Diabetic Ketoacidosis Secondary to SGLT2-inhibitor Use in Combination With a Ketogenic Diet

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.776 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A380-A381

Author(s):

Joi C Hester ◽

Stacy Zimmerman ◽

Teresa Allison Nimmo ◽

Wesley Cunningham ◽

Joshua Liu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Blood Glucose ◽

Diabetic Ketoacidosis ◽

Ketogenic Diet ◽

Sglt2 Inhibitor ◽

Perioperative Period ◽

Anion Gap ◽

Arterial Blood ◽

Euglycemic Diabetic Ketoacidosis

Abstract Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are cardiorenal protective agents increasingly used in patients with diabetes. Cases of euglycemic diabetic ketoacidosis (euDKA) have been reported particularly among patients with type 1 diabetes. Our case is an example that highlights the role SGLT-2 inhibitors play in the development of euDKA in a patient with type 2 diabetes with confounding factors of strict adherence to a ketogenic diet and ankle fracture. A 72-year-old female with a history of type 2 diabetes presented to the emergency department (ED) with right ankle pain and obvious deformity after a mechanical fall. Radiography of the right lower extremity confirmed distal fracture of the tibia and fibula. After reduction of her fracture in the ED, she was admitted in anticipation of an open reduction internal fixation. Her diabetes was controlled on empagliflozin monotherapy and adhering to a ketogenic diet. She monitored her blood ketones daily at home and reported values in the 3–4 mmol/L range. On admission, her basic metabolic panel (BMP) revealed a blood glucose of 148 mg/dL, bicarbonate of 20 mEq/L, anion gap of 18 mEq/L, Cr of 1.3 mg/dl, and eGFR of 40 mL/min. Her beta-hydroxybutyrate (BHB) was 5.09 mmol/L. The initial assessment was presumed starvation ketosis. On hospital day three, she complained of continued nausea, polydipsia, and abdominal pain. Chart review revealed nocturia with approximately 3–4 voids per night. Repeat BMP showed a blood glucose of 152 mg/dL, bicarbonate of 16 mEq/L, anion gap still at 18 mEq/L, Cr 1.4 mg/dl, and eGFR of 37 mL/min. Since admission, all of her blood glucose levels ranged between 118–178 mg/dL. She denied dyspnea but exhibited Kussmaul respirations on physical exam. Repeat labs revealed a BHB of 8.92 mmol/L, and arterial blood gas (ABG) showed pH 7.2, pCO2 23, pO2 100, bicarbonate 8.6 mEq/L, consistent with high-anion gap metabolic acidosis, confirming the diagnosis of euDKA. Her empagliflozin had been held since admission, but she had not received any insulin up to this point due to euglycemia. She was immediately started on a weight-based dose of 12 units of insulin glargine with subsequent improvement of her BHB and anion gap. This patient’s use of an SGLT2-inhibitor in combination with her being on a ketogenic diet, contributed to a nonregulated state of ketone production leading to euDKA in the perioperative period. As SGLT2-inhibitors become more readily available, it is important to educate physicians and patients about the risk of euDKA during fasting, ketogenic diets, and the perioperative period.

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