Drug class: Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors

Medically reviewed by Drugs.com on Apr 10, 2025. Written by ASHP.

Introduction

Sodium-glucose cotransporter 2 (SGLT2) inhibitor; antidiabetic agent.

Uses for Bexagliflozin

Type 2 Diabetes Mellitus

Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Used as monotherapy and in combination with metformin for treatment of type 2 diabetes mellitus.

Not recommended to improve glycemic control in patients with type 1 diabetes mellitus.

Guidelines from the American Diabetes Association (ADA) and other experts generally recommend the use of SGLT2 inhibitors or glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes and established/high risk of atherosclerotic cardiovascular disease (ASCVD), heart failure, and/or chronic kidney disease. When selecting treatment regimen, consider factors such as cardiovascular and renal comorbidities, drug efficacy and adverse effects, hypoglycemic risk, presence of overweight or obesity, cost, access, and patient preferences. Weight management should be included as a distinct treatment goal, and other healthy lifestyle behaviors should be considered.

Bexagliflozin Dosage and Administration

General

Pretreatment Screening

• Assess renal function.

• Assess volume status. In patients with volume depletion, correct this condition before initiating bexagliflozin.

• Before initiation, consider factors in the patient history that may predispose to the need for amputations, such as history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.

Patient Monitoring

• Assess renal function periodically during treatment as clinically indicated.

• Consider ketone monitoring in patients at risk for ketoacidosis if indicated by clinical situation.

• Assess for ketoacidosis regardless of presenting blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis.

• Monitor for signs and symptoms of volume depletion and renal function.

• Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated.

• Monitoring of glycemic control with urine glucose tests is not recommended in patients taking bexagliflozin due to known increase in urinary glucose excretion, leading to positive urine glucose tests. Use alternate methods to monitor glycemic control.

• Measurements of 1,5-anhydroglucitol are unreliable in assessing glycemic control in patients taking sodium-glucose cotransporter 2 inhibitors. Monitoring of glycemic control with 1,5-anhydroglucitol assay is not recommended. Use alternative methods to monitor glycemic control.

Administration

Administer orally as tablets.

Take in the morning with or without food; do not crush or chew tablets.

If dose is missed, take missed dose as soon as possible. Do not double next dose.

Withhold for at least 3 days, if possible, prior to major surgery or procedures associated with prolonged fasting. Resume when patient clinically stable and has resumed oral intake.

Dosage

Adults

Type 2 Diabetes Mellitus

Oral

20 mg once daily.

Special Populations

Hepatic Impairment

No dosage adjustments for mild to moderate hepatic impairment. Not recommended for use in severe hepatic impairment.

Renal Impairment

No dosage adjustments needed for eGFR ≥30 mL/minute per 1.73 m². Not recommended for use in eGFR <30 mL/minute per 1.73 m².

Geriatric Patients

No specific population dosage recommendations at this time.

Cautions for Bexagliflozin

Contraindications

• Hypersensitivity to bexagliflozin or any excipient in the formulation. Anaphylaxis and angioedema have been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors.

Warnings/Precautions

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus or Other Ketoacidosis

In patients with type 1 diabetes mellitus, bexagliflozin significantly increases risk of diabetic ketoacidosis (a life-threatening event) beyond background rate. Bexagliflozin is not indicated for glycemic control in type 1 diabetes mellitus.

Patients with type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also at risk for ketoacidosis. There have been postmarking reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors.

Precipitating conditions include under-insulinization due to insulin dosage reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse. Signs and symptoms are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Blood glucose levels at presentation may be below those typically expected for diabetic ketoacidosis (e.g., <250 mg/dL). Ketoacidosis and glucosuria may persist longer than typically expected. Urinary glucose excretion persists for 3 days after discontinuation; however, there have been postmarketing reports of ketoacidosis and/or glucosuria lasting >6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors.

Consider ketone monitoring in patients at risk for ketoacidosis if indicated by clinical situation. Assess for ketoacidosis regardless of blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis. If ketoacidosis is suspected, discontinue bexagliflozin, promptly evaluate, and treat ketoacidosis, if confirmed. Monitor for resolution of ketoacidosis before restarting.

Withhold bexagliflozin, if possible, in temporary clinical situations that could predispose to ketoacidosis. Resume when the patient is clinically stable and has resumed oral intake.

Educate all patients on signs and symptoms of ketoacidosis and instruct patients to discontinue bexagliflozin and seek medical attention immediately if signs and symptoms occur.

Lower Limb Amputation

Increased incidence of lower limb amputations occurred in bexagliflozin-treated compared to placebo-treated patients (8.3 versus 5.1 events per 1000 patients-years) in a randomized, placebo-controlled trial evaluating patients with type 2 diabetes mellitus who had either established or were at risk for cardiovascular disease. Of the 23 patients who had amputations, 15 were amputations of toe and midfoot and 8 were amputations above and below the knee. Some had multiple amputations.

Lower limb infections, gangrene, ischemia, and osteomyelitis were most common precipitating events leading to need for amputation. Risk of amputation was highest in patients with baseline history of prior amputation, peripheral vascular disease, and neuropathy.

Before initiating, consider factors in history that may predispose to need for amputations, such as history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. Counsel patients on importance of routine preventative foot care. Monitor patients for signs and symptoms of infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving lower limbs, and discontinue bexagliflozin if these complications occur.

Volume Depletion

Can cause intravascular volume contraction, which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors. Patients with impaired renal function (eGFR rate <60 mL/minute per 1.73 m²), elderly, low systolic blood pressure, or on loop diuretics may be at increased risk for volume depletion or hypotension.

Before initiating in patients with one or more of these characteristics, assess volume status and renal function. In patients with volume depletion, correct this condition before initiating therapy. Monitor for signs and symptoms of volume depletion and renal function after initiation.

Urosepsis and Pyelonephritis

There have been reports of serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization in patients receiving SGLT2 inhibitors, including bexagliflozin.

Treatment with SGLT2 inhibitors increases risk of urinary tract infections. Evaluate for signs and symptoms of urinary tract infections and treat promptly, if indicated.

Hypoglycemia with Concomitant Use of Insulin and Insulin Secretagogues

Bexagliflozin may increase the risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue (e.g., sulfonylurea). Lower dosage of insulin or insulin secretagogue may be required to minimize risk of hypoglycemia when used in combination with bexagliflozin.

Necrotizing Fasciitis of the Perineum (Fournier's Gangrene)

Reports of necrotizing fasciitis of perineum (Fournier’s Gangrene), a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have occurred. Cases have been reported in both females and males. Serious outcomes have included hospitalization, multiple surgeries, and death.

Patients presenting with pain or tenderness, erythema, or swelling in genital or perineal areas, along with fever or malaise, should be assessed for necrotizing fasciitis. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue bexagliflozin, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.

Genital Mycotic Infections

Increases risk of genital mycotic infection. Patients who have history of genital mycotic infections or who are uncircumcised are more likely to develop genital mycotic infections. Monitor and treat appropriately.

Specific Populations

Pregnancy

Insufficient evidence in pregnant women to evaluate drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Based on animal data showing adverse renal effects, not recommended during second and third trimesters of pregnancy.

There are risks to mother and fetus associated with poorly controlled diabetes in pregnancy. Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes. Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.

Lactation

No data on presence of bexagliflozin in human milk, effects on breast-fed child, or effects on milk production. Excreted into the milk of lactating rats. When drug present in animal milk, it is likely that drug will be present in human milk. Since human kidney maturation occurs in utero and during first 2 years of life when lactational exposure may occur, there may be a risk to the developing human kidney. Because of potential for serious adverse reactions in breast-fed child, including potential to affect postnatal renal development, advise patients that use of bexagliflozin is not recommended while breastfeeding.

Pediatric Use

Safety and effectiveness not established.

Geriatric Use

No overall differences in the effectiveness of bexagliflozin have been observed between patients aged ≥65 years and older and younger adult patients.

Hepatic Impairment

Not studied in severe hepatic impairment and not recommended for use in this population. Recommended dosage for mild to moderate hepatic impairment same as recommended dosage for normal hepatic function.

Renal Impairment

Patients with renal impairment may be more likely to experience adverse reactions, including female genital mycotic infection, increased urination, and thirst, and may be at higher risk for volume depletion and acute kidney injury.

Glucose-lowering pharmacodynamic response declines with increasing severity of renal impairment.

Safety and efficacy of bexagliflozin in adults with type 2 diabetes mellitus have been established in moderate renal impairment (eGFR between 30 and 60 mL/minute per 1.73 m²). Recommended dosage in eGFR ≥30 mL/minute per 1.73 m² is same as normal renal function. Impact of hemodialysis not known.

Not recommended in eGFR <30 mL/minute per 1.73 m² due to decline of the glucose lowering effect and reduction in urine output.

Common Adverse Effects

Most common adverse effects (>5%): female genital mycotic infections, urinary tract infection, increased urination.

Drug Interactions

Mainly metabolized by uridine diphosphate-glucuronosyl transferase (UGT) 1A9, and, to lesser extent, CYP3A.

Substrate for P-glycoprotein (P-gp).

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Not expected to inhibit CYP isoenzymes CYP1A2, CYP2B6, CYP2C8, 2C9, 2C19, 2D6, and 3A4, or induce CYP1A2, CYP2C19, and CYP3A4 at clinically relevant plasma concentrations.

Drugs Affecting or Affected by Transport Systems

Not expected to inhibit breast cancer resistance protein (BCRP), bile salt export pump (BSEP), organic anion transporting polypeptide (OATP) 1B1 or OATP1B3, organic anion transporter (OAT) 1 or OAT3, organic cation transporter (OCT) 1 or OCT2, and multidrug and toxic extrusion transporters (MATE) 1 or MATE2-K at clinically relevant plasma concentrations.

UGT enzyme inducers may significantly reduce exposure to bexagliflozin and lead to decreased efficacy. Consider adding another antihyperglycemic agent in patients who require additional glycemic control.

Specific Drugs

Bexagliflozin Pharmacokinetics

Absorption

Bioavailability

Plasma C_max and AUC increase in dose-proportional manner following single doses from 3 to 90 mg.

Accumulates in plasma up to ~20% following multiple dosing.

Onset

Peak plasma concentrations (C_max) reached between 2—4 hours post-dose; delayed if taken after meal or medications that slow gastric emptying.

Effect of Food

Administration after consumption of standard high-fat, high-caloric meal increases C_max and AUC by 31% and 10%, respectively, compared to fasted state; median time to maximum plasma concentration (T_max) increased to 5 hours.

Effects of food not considered clinically relevant.

Special Populations

In mild (eGFR 60—89 mL/minute per 1.73 m²), moderate (eGFR 30—59 mL/minute per 1.73 m²), and severe (eGFR <30 mL/minute per 1.73 m²) renal impairment, AUC is 7%, 34%, and 54% greater than in normal renal function, respectively, after single dose. This increase in AUC is not considered clinically meaningful; however, glucose-lowering pharmacodynamic response declines with increasing severity of renal impairment. Impact of hemodialysis is not known.

In moderate hepatic impairment (Child-Pugh class B), AUC increases 28% and C_max increases by 6.3% compared to normal hepatic function. These increases are not considered clinically meaningful. No clinical experience in severe (Child-Pugh class C) hepatic impairment.

Distribution

Extent

Likely distributed into human breast milk.

Plasma Protein Binding

93%.

Elimination

Metabolism

Metabolized by uridine diphosphate-glucuronosyl transferase (UGT) 1A9, and, to lesser extent, CYP3A.

Elimination Route

Excreted in feces (51.1%), majority as unchanged drug, and urine (40.5%), largely as 3’-O-glucuronide metabolite.

Half-life

Approximately 12 hours.

Special Populations

Age, body weight, sex, and race do not have clinically relevant effect on pharmacokinetics.

Pharmacokinetics similar in healthy subjects and adults with type 2 diabetes mellitus.

Stability

Storage

Oral

Tablets, film-coated

Store at 20-25°C; excursions permitted between 15-30°C.

Actions

• Inhibitor of sodium-glucose cotransporter 2 (SGLT2), the transporter responsible for reabsorption of the majority of glucose from the renal glomerular filtrate in the renal proximal tubule.

• By inhibiting SGLT2, reduces renal reabsorption of filtered glucose and lowers renal threshold for glucose, and thereby increases urinary glucose excretion.

• Provides near-maximal urinary glucose excretion; increases in urinary glucose excretion accompanied by increases in urine volume.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Medication Guide).

• Inform patients that bexagliflozin can cause potentially fatal ketoacidosis and that type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are risk factors. Educate all patients on precipitating factors, such as insulin dosage reduction or missed insulin doses, infection, reduced caloric intake, ketogenic diet, surgery, dehydration, and alcohol abuse, and symptoms of ketoacidosis (including nausea, vomiting, abdominal pain, tiredness, and labored breathing). Inform patients that blood glucose may be normal even in the presence of ketoacidosis. Advise patients that they may be asked to monitor ketones. If symptoms of ketoacidosis occur, instruct patients to discontinue bexagliflozin and seek medical attention immediately.

• Inform patients of the potential for an increased risk of amputations with bexagliflozin. Counsel patients on the importance of routine preventative foot care. Instruct patients to monitor for any new pain or tenderness, sores or ulcers, or infections involving the leg or foot and to seek medical advice immediately if such signs or symptoms develop.

• Inform patients that symptomatic hypotension may occur with bexagliflozin and advise them to contact their clinician if they experience such symptoms. Advise them to seek medical advice if such symptoms occur.

• Inform patients of the potential for urinary tract infections, which may be serious. Provide patients with information on the symptoms of urinary tract infections. Advise patients to seek medical advice if such symptoms occur.

• Inform patients that the incidence of hypoglycemia may increase when bexagliflozin is added to insulin and/or an insulin secretagogue. Educate patients or caregivers on the signs and symptoms of hypoglycemia.

• Inform patients that necrotizing infections of the perineum (Fournier’s Gangrene) have occurred with bexagliflozin. Counsel patients to promptly seek medical attention if they develop pain or tenderness, redness or swelling of the genitals or the area from the genitals to the anus, accompanied by a fever above 38°C (100.4°F) or malaise.

• Inform female patients that vaginal yeast infections may occur and provide them with information on the signs and symptoms of vaginal yeast infections. Advise patients of treatment options and when to seek medical advice.

• Inform male patients that yeast infections of the penis (e.g., balanitis or balanoposthitis) may occur, especially in uncircumcised males and patients with prior infections. Provide patients with information on the signs and symptoms of balanitis and balanoposthitis (rash or redness of the glans or foreskin of the penis). Advise patients of treatment options and when to seek medical advice.

• Advise pregnant patients and females of reproductive potential of the potential risk to a fetus with treatment with bexagliflozin. Instruct patients to inform their clinician if they are pregnant or are planning to become pregnant.

• Advise patients that breastfeeding is not recommended during treatment with bexagliflozin.

• Inform patients that their urine will test positive for glucose while taking bexagliflozin due to its mechanism of action.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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