Bexagliflozin

Indications

• Type 2 diabetes mellitus (T2DM)

Dosage

Children: Refer to the BNF for Children for specific dosing guidance.

Adults: Refer to the BNF for specific dosing guidance.

Mechanism of action

Bexagliflozin inhibits the sodium-glucose co-transporter 2 (SGLT2) located in the proximal renal tubule, which is responsible for the reabsorption of glucose and sodium. By blocking this transporter, bexagliflozin decreases glucose reabsorption in the kidneys and promotes its excretion in urine, thus lowering blood glucose levels independently of insulin sensitivity.

Pharmacodynamics

In healthy individuals and adults with type 2 diabetes, bexagliflozin induces dose-dependent increases in urinary glucose excretion (UGE) and urine volume. A 20 mg dose achieves near-maximal UGE, which is sustained with multiple doses. Bexagliflozin does not significantly prolong the QTc interval even at five times the recommended dose. Possible adverse effects include ketoacidosis, volume depletion, urinary tract infections, and an increased risk of lower limb amputation compared to placebo, particularly in patients using insulin or insulin secretagogues.

Pharmacokinetics

The pharmacokinetics of bexagliflozin involves absorption, distribution, metabolism, and excretion characteristics that are typical for SGLT2 inhibitors. However, specific details regarding its absorption rate, half-life, and clearance are not provided. The drug is primarily excreted via the renal route, correlating with its mechanism of action.

Contra-indications

• Severe renal impairment (eGFR < 30 mL/min)
• Diabetic ketoacidosis
• Hypersensitivity to bexagliflozin or any excipients

Adverse effects

• Ketoacidosis
• Volume depletion
• Urosepsis
• Pyelonephritis
• Necrotizing fasciitis of the perineum
• Genital mycotic infections
• Increased incidence of lower limb amputation
• Hypoglycemia when used with insulin or insulin secretagogues

Interactions

• Increased risk of hypoglycemia when used with insulin and insulin secretagogues
• Potential for additive diuretic effect when used with other diuretics

Precautions

• Monitor renal function before and during treatment
• Assess for signs and symptoms of urinary tract infections
• Monitor for volume depletion and orthostatic hypotension
• Consider risk of ketoacidosis, especially in patients with risk factors

Pregnancy

There is limited data on the use of bexagliflozin in pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether bexagliflozin is excreted in human breast milk. Caution is advised when administering to breastfeeding women.

Storage

Store at 20°C to 25°C. Protect from light and moisture.

Formulations

• Tablets: 5 mg, 10 mg

Mechanism of action

Bexagliflozin is a highly selective sodium–glucose co-transporter 2 (SGLT2) inhibitor. SGLT2 is located in the proximal renal tubule, a part of the kidney where most reabsorption takes place, and they transport glucose and sodium from the tubular lumen to the epithelium. By inhibiting SGLT2, bexagliflozin reduces glucose reabsorption in the kidney and promotes its excretion in urine. Therefore, in patients with type 2 diabetes mellitus (T2DM), bexagliflozin reduces blood glucose levels independently of insulin sensitivity. Aside from improving glycemic control, bexagliflozin may also reduce body weight, systolic blood pressure, and albuminuria. The mechanism of action for these other effects have not been fully elucidated, but it is possible that they depend on the initial natriuresis caused by bexagliflozin, followed by a change in tissue sodium handling.

Pharmacodynamics

Healthy subjects and adults with type 2 diabetes mellitus given single or multiple doses of bexagliflozin had dose-dependent increases in urinary glucose excretion (UGE) accompanied by increases in urine volume. A 20 mg bexagliflozin dose can provide near-maximal UGE, and elevated UGE values are maintained with multiple-dose administration. Bexagliflozin does not cause clinically significant QTc interval prolongation at 5 times the recommended dose. The use of bexagliflozin may cause ketoacidosis, volume depletion, urosepsis, pyelonephritis, necrotizing fasciitis of the perineum and genital mycotic infections. There is also an increased incidence of lower limb amputation in patients treated with bexagliflozin compared to those receiving a placebo. In addition, the use of bexagliflozin in patients treated with insulin and insulin secretagogues may increase the risk of hypoglycemia.