Bexagliflozin (Brenzavvy™): A Comprehensive Monograph on a Novel SGLT2 Inhibitor for Glycemic Control

Executive Summary & Drug Classification

Introduction to Bexagliflozin

Bexagliflozin is an orally administered, potent, and highly selective small molecule inhibitor of the sodium-glucose cotransporter 2 (SGLT2).[1] Developed by TheracosBio, LLC, and marketed under the brand name Brenzavvy™, it represents a significant addition to the therapeutic armamentarium for the management of type 2 diabetes mellitus (T2DM).[3] On January 20, 2023, bexagliflozin received approval from the U.S. Food and Drug Administration (FDA), becoming the fifth orally administered SGLT2 inhibitor to enter the U.S. market for this indication, following the precedent set by dapagliflozin, canagliflozin, empagliflozin, and ertugliflozin.[4] Its approval was supported by a comprehensive clinical development program involving 23 trials and over 5,000 adult participants, which established its efficacy in improving glycemic control as an adjunct to diet and exercise.[6]

The entry of bexagliflozin into a well-established and competitive therapeutic class necessitates a careful evaluation of its distinct characteristics. In a market with several incumbent SGLT2 inhibitors, each with extensive clinical data and established patterns of use, a new agent must demonstrate compelling value to secure a place in clinical practice. This value may manifest as superior efficacy or safety in the general population or specific subgroups, a novel indication, an improved tolerability profile, or a more favorable pharmacoeconomic profile. The clinical data for bexagliflozin suggests potential advantages in specific, challenging patient populations, such as those with moderate chronic kidney disease, while its manufacturer has pursued a market access strategy centered on transparent and affordable pricing, positioning it as a potentially disruptive force in the landscape of modern diabetes care.[8]

Therapeutic Class and Context

Bexagliflozin belongs to the therapeutic class of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors, a group of oral antidiabetic agents also known as "gliflozins".[1] This class of drugs has fundamentally altered the management of T2DM over the past decade. Their unique, insulin-independent mechanism of action—promoting urinary glucose excretion by inhibiting glucose reabsorption in the kidneys—provides effective glycemic control at various stages of the disease.[1]

Beyond their glucose-lowering effects, SGLT2 inhibitors as a class have demonstrated a range of pleiotropic benefits that address the multifaceted nature of T2DM and its associated comorbidities. Large-scale cardiovascular outcomes trials (CVOTs) for other agents in this class have consistently shown reductions in major adverse cardiovascular events, hospitalizations for heart failure, and the progression of renal disease.[11] These landmark findings have led to expanded indications for certain SGLT2 inhibitors in the treatment of heart failure (with or without diabetes) and chronic kidney disease, elevating their status from simple glucose-lowering drugs to cornerstone therapies for cardio-renal protection.[5] Consequently, major clinical practice guidelines now recommend the use of SGLT2 inhibitors with proven benefit for patients with T2DM and established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, often independent of baseline hemoglobin A1c (HbA1c) levels.[5] Bexagliflozin enters this therapeutic landscape with the expectation of providing similar class-wide benefits, including modest but consistent reductions in body weight and systolic blood pressure, which were observed throughout its clinical trial program.[1]

Summary of Key Attributes

Bexagliflozin is a potent and highly selective SGLT2 inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2DM.[1] Its mechanism involves the inhibition of renal glucose reabsorption, leading to glycosuria and a reduction in plasma glucose levels through a pathway that does not depend on insulin secretion or sensitivity.[13] It is administered as a 20 mg oral tablet once daily.[3]

Regulatory approval was granted by the U.S. FDA in January 2023.[7] Consistent with its class, bexagliflozin carries important safety considerations, including warnings for diabetic ketoacidosis (DKA), lower limb amputation, volume depletion, serious urinary tract infections, and genital mycotic infections.[1] It is not recommended for the treatment of type 1 diabetes mellitus due to an elevated risk of DKA.[1] A notable and unique aspect of bexagliflozin is its dual approval for both human and veterinary use; under the brand name Bexacat™, it is the first SGLT2 inhibitor approved by the FDA for improving glycemic control in cats with diabetes mellitus, underscoring a broad therapeutic window and a well-characterized safety profile across species.[6]

Chemical Profile and Physicochemical Properties

Chemical Identification

The unambiguous identification of a pharmaceutical substance is critical for regulatory, clinical, and research purposes. Bexagliflozin is cataloged across numerous international chemical and pharmacological databases under a consistent set of identifiers.

• Generic Name: Bexagliflozin [1]
• DrugBank ID: DB12236 [1]
• Type: Small Molecule [1]
• CAS (Chemical Abstracts Service) Number: 1118567-05-7 [6]
• IUPAC (International Union of Pure and Applied Chemistry) Name: (2S,3R,4R,5S,6R)-2-[4-chloro-3-({4-[2-(cyclopropyloxy)ethoxy]phenyl}methyl)phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol [6]
• Other Key Identifiers:
• UNII (Unique Ingredient Identifier): EY00JF42FV [6]
• ChEBI (Chemical Entities of Biological Interest): CHEBI:229225 [6]
• ChEMBL ID: CHEMBL1808388 [6]
• KEGG (Kyoto Encyclopedia of Genes and Genomes) ID: D10865 [6]

Molecular Structure and Class

Bexagliflozin is classified chemically as a C-glycosyl compound, a structural feature that is central to its function and viability as an oral therapeutic agent.[11] It belongs to the C-aryl glucoside subclass, which is characteristic of the modern gliflozin drugs.[16] The molecular architecture of bexagliflozin comprises three essential moieties: a central glucose ring, two flanking benzene rings, and a methylene bridge that connects them.[1] This core scaffold is responsible for the molecule's high-affinity binding to the SGLT2 transporter protein.

The specific substitutions on this scaffold confer bexagliflozin's unique pharmacological properties. The aglycone portion of the molecule consists of a 4-chloro-3-({4-[2-(cyclopropyloxy)ethoxy]phenyl}methyl)phenyl group, which is covalently bonded to the anomeric carbon of the β-D-glucose ring.[13] This C-C bond is a critical chemical innovation. The first identified SGLT inhibitor, phlorizin (an O-glycoside derived from apple tree bark), was unsuitable for oral therapy because its O-glycosidic bond was readily cleaved by β-glucosidase enzymes in the gastrointestinal tract, leading to poor absorption and systemic bioavailability.[10] The development of C-glycosyl compounds like bexagliflozin, where the anomeric oxygen is replaced by a carbon atom, creates a bond that is resistant to enzymatic hydrolysis. This structural stability is fundamental to the success of the entire gliflozin class, enabling effective oral administration and sustained systemic exposure.[10]

Physicochemical Properties

The physical and chemical properties of bexagliflozin dictate its formulation, stability, and pharmacokinetic behavior. These properties are consistent with a molecule designed for oral bioavailability and align with established principles of medicinal chemistry, such as Lipinski's Rule-of-Five, which predicts "druglikeness".[17]

• Molecular Formula: C24​H29​ClO7​ [1]
• Molecular Weight:
• Average: 464.94 g/mol [1]
• Monoisotopic: 464.160181 g/mol [1]
• Physical Form: Bexagliflozin is described as a white to light yellow crystalline solid or powder.[21]
• Solubility: It is characterized as "slightly soluble" in aqueous media, a property that influences its dissolution rate in the gastrointestinal tract.[13] In organic solvents, it is highly soluble in dimethyl sulfoxide (DMSO), with a reported solubility of at least 100 mg/mL.[20]
• Dissociation Constant (pKa): The molecule contains several hydroxyl groups, which are weakly acidic. The predicted acidic pKa is approximately 12.57 to 13.23, indicating that the molecule will remain in a neutral, un-ionized state under physiological pH conditions.[21]
• Lipophilicity: The partition coefficient, a measure of lipophilicity, is reported as an XLogP3 value of 2.4.[25] This moderate lipophilicity balances the aqueous solubility required for dissolution with the lipid permeability needed for absorption across biological membranes.

Synonyms and Code Names

Throughout its development and into its commercialization, bexagliflozin has been known by several names. These synonyms are important for comprehensively searching scientific literature and regulatory documents.

• Commercial Brand Names: Brenzavvy™ (human), Bexacat™ (veterinary) [1]
• Developmental Code Names: EGT-1442, EGT-0001442, THR-1442 [2]

It is important to note that some commercial sources may contain inaccuracies. For instance, one supplier's description incorrectly identifies bexagliflozin's mechanism as DPP-IV inhibition.[26] This is factually erroneous, as bexagliflozin is definitively an SGLT2 inhibitor. Such discrepancies underscore the necessity of relying on authoritative sources such as regulatory filings, drug databases like DrugBank, and peer-reviewed scientific publications for accurate pharmacological information.

Table 1: Chemical and Physical Properties of Bexagliflozin

Property	Value	Source(s)
Generic Name	Bexagliflozin	1
Chemical Class	C-aryl glucoside SGLT2 inhibitor	11
IUPAC Name	(2S,3R,4R,5S,6R)-2-[4-chloro-3-({4-[2-(cyclopropyloxy)ethoxy]phenyl}methyl)phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol	6
CAS Number	1118567-05-7	6
DrugBank ID	DB12236	1
Molecular Formula	C24​H29​ClO7​	1
Molecular Weight	Average: 464.94 g/mol; Monoisotopic: 464.160181 g/mol	1
Physical Appearance	White to light yellow crystalline solid/powder	21
Solubility	Aqueous: Slightly soluble; DMSO: ≥ 100 mg/mL	13
Predicted pKa	12.57–13.23 (acidic)	21
XLogP3	2.4	25

Comprehensive Pharmacological Profile

Pharmacodynamics (Mechanism of Action)

The therapeutic effects of bexagliflozin are derived from its highly specific and potent inhibition of the sodium-glucose cotransporter 2.

Primary Target and Physiological Context

The primary molecular target of bexagliflozin is the sodium-glucose cotransporter 2 (SGLT2), a high-capacity, low-affinity transport protein located almost exclusively on the apical membrane of epithelial cells in the S1 and S2 segments of the renal proximal tubule.[1] Under normal physiological conditions, the kidneys filter approximately 180 grams of glucose from the plasma into the glomerular filtrate each day. To conserve this vital energy source, nearly all of this filtered glucose is reabsorbed back into circulation.[11] The SGLT2 transporter is the principal mediator of this process, responsible for the reabsorption of 60% to 90% of the filtered glucose load.[1] It functions by coupling the transport of one molecule of glucose with one sodium ion (

Na+) down the electrochemical gradient of sodium, effectively moving glucose from the tubular lumen into the epithelial cell against its concentration gradient.[11]

Mechanism of Inhibition and Glycemic Effects

Bexagliflozin functions as a competitive and reversible inhibitor of SGLT2.[1] By binding to the transporter, it physically blocks the reabsorption of glucose and sodium from the glomerular filtrate. This inhibition effectively lowers the renal threshold for glucose (RTG)—the plasma glucose concentration above which glucose begins to appear in the urine. In healthy individuals, the RTG is approximately 180 mg/dL, but in patients with T2DM, it is often upregulated, contributing to the maintenance of hyperglycemia. SGLT2 inhibitors like bexagliflozin lower the RTG to a new, much lower set point, causing a therapeutic glycosuria (urinary glucose excretion, UGE) at plasma glucose concentrations that would not normally result in glucose spilling.[14] A 20 mg dose of bexagliflozin provides near-maximal UGE, an effect that is sustained with chronic administration.[1] This process results in the net loss of glucose from the body, leading to a reduction in fasting and postprandial plasma glucose levels and, consequently, a decrease in HbA1c.[1]

Insulin-Independent Action

A defining and clinically crucial feature of the SGLT2 inhibitor class, including bexagliflozin, is that their mechanism of action is entirely independent of pancreatic β-cell function and systemic insulin sensitivity.[1] Unlike insulin secretagogues (e.g., sulfonylureas) or insulin sensitizers (e.g., metformin, thiazolidinediones), bexagliflozin does not rely on the presence of endogenous insulin secretion or the body's response to insulin to exert its glucose-lowering effect. This makes it an effective therapeutic option across the full spectrum of T2DM, from early stages where insulin resistance is predominant to later stages characterized by significant β-cell failure. This independence also allows it to be used effectively in combination with virtually all other classes of antidiabetic agents, providing an additive glucose-lowering effect through a complementary mechanism.[10] Furthermore, because its action is glucose-dependent (i.e., it only promotes the excretion of glucose that has been filtered), the risk of hypoglycemia when used as monotherapy is very low.[5]

Potency and Selectivity

Bexagliflozin is characterized by its high potency and remarkable selectivity for SGLT2. In vitro assays have demonstrated a half-maximal inhibitory concentration (IC50​) of approximately 2 nM for human SGLT2.[2] This indicates very high-affinity binding to its target.

Equally important is its selectivity over the related transporter, SGLT1. SGLT1 is a high-affinity, low-capacity transporter found predominantly in the small intestine, where it is responsible for the absorption of dietary glucose and galactose, and to a lesser extent in the S3 segment of the renal proximal tubule, where it reabsorbs the small amount of glucose that escapes SGLT2.[1] Bexagliflozin exhibits an

IC50​ for human SGLT1 of approximately 5.6 μM (5600 nM).[18] This results in a selectivity ratio of over 2400-fold for SGLT2 over SGLT1.[18] This high degree of selectivity is clinically significant. Potent inhibition of intestinal SGLT1 can lead to glucose-galactose malabsorption, causing gastrointestinal side effects such as diarrhea and dehydration. By selectively targeting SGLT2, bexagliflozin minimizes these off-target effects, contributing to a more favorable tolerability profile.

Pharmacokinetics (ADME Profile)

The pharmacokinetic profile of bexagliflozin describes its absorption, distribution, metabolism, and excretion (ADME), which collectively determine its dosing regimen and potential for drug interactions. Its properties are well-suited for once-daily oral administration.

Absorption

Following oral administration, bexagliflozin is readily absorbed. In the fasted state, peak plasma concentrations (Cmax​) are achieved within a median time (Tmax​) of 2 to 4 hours.[1] The pharmacokinetics are dose-proportional over a clinically relevant range.[1] Administration with a standard high-fat, high-calorie meal has a modest effect on its absorption profile, delaying the median

Tmax​ to 5 hours and increasing the Cmax​ and area under the concentration-time curve (AUC) by 31% and 10%, respectively.[1] These changes are not considered clinically significant, which allows for flexible dosing with or without food, enhancing patient convenience and adherence.[29]

Distribution

Once absorbed into the systemic circulation, bexagliflozin is extensively distributed throughout the body. It exhibits a large apparent volume of distribution (Vd​) of 262 L, indicating significant partitioning from the plasma into extravascular tissues.[1] Bexagliflozin is also highly bound to plasma proteins, with a bound fraction of approximately 93%.[1] This high degree of protein binding limits the amount of free, pharmacologically active drug in circulation at any given time and can influence its distribution and elimination characteristics.

Metabolism

Bexagliflozin undergoes metabolism primarily in the liver.[1] The major metabolic pathway is glucuronidation, a Phase II conjugation reaction mediated predominantly by the uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) enzyme.[1] This process forms the 3'-O-glucuronide metabolite, which is pharmacologically inactive and constitutes the largest fraction of circulating metabolites, accounting for approximately 32% of the parent drug's AUC in humans.[1] A minor metabolic pathway involves Phase I oxidation mediated by the cytochrome P450 3A (CYP3A) isoenzyme.[1]

The reliance on UGT1A9 for primary metabolism has important clinical implications for drug-drug interactions. While this pathway avoids many common interactions involving the major CYP450 enzymes (e.g., CYP2C9, CYP2D6), it creates a specific susceptibility to interactions with potent inducers of UGT enzymes. Drugs that strongly induce UGT1A9 can accelerate the clearance of bexagliflozin, leading to reduced systemic exposure and potentially diminished glycemic efficacy.[27] This necessitates clinical vigilance when such agents are co-administered.

Excretion

Bexagliflozin and its metabolites are eliminated from the body through both renal and fecal routes. The apparent terminal elimination half-life (t1/2​) is approximately 12 hours, a duration that supports a convenient once-daily dosing schedule.[1] Following administration of a single oral radiolabeled dose, approximately 91.6% of the radioactivity was recovered. Of this, 51.1% was found in the feces, predominantly as unchanged parent drug, suggesting that a portion of the absorbed drug is secreted into the bile or that some of the oral dose is not absorbed. The remaining 40.5% was recovered in the urine, largely in the form of the inactive 3'-O-glucuronide metabolite.[11] Only a very small fraction (1.5%) of the dose was excreted as unchanged bexagliflozin in the urine.[1] The apparent oral clearance of bexagliflozin is 19.1 L/h.[1]

Table 2: Key Pharmacokinetic Parameters of Bexagliflozin

Parameter	Value	Source(s)
Tmax​ (Time to Peak Concentration)	2–4 hours (fasted); 5 hours (fed)	1
Effect of Food on Bioavailability	Not clinically significant	27
Volume of Distribution (Vd​)	262 L	1
Plasma Protein Binding	~93%	1
Primary Metabolism Pathway	UGT1A9 Glucuronidation	1
Major Metabolite	3'-O-glucuronide (inactive)	1
Elimination Half-Life (t1/2​)	~12 hours	1
Route of Excretion	Feces (~51.1%); Urine (~40.5%)	11

Clinical Efficacy and Therapeutic Applications

Approved Indications, Dosage, and Administration

Indication

Bexagliflozin is officially indicated by the U.S. FDA as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.[1] This indication positions it as a component of a comprehensive diabetes management strategy that includes lifestyle modification as its foundation.

Dosage and Administration

The recommended and approved dosage of bexagliflozin is a 20 mg tablet administered orally once daily, typically in the morning.[3] Administration can be done with or without food, providing flexibility for the patient.[29] The tablets are formulated to be swallowed whole and should not be crushed, split, or chewed, to ensure proper release and absorption of the active ingredient.[30] If a dose is missed, it should be taken as soon as the patient remembers; however, the patient should not take two doses at the same time to make up for a missed dose.[29]

Limitations of Use

The prescribing information for bexagliflozin includes important limitations on its use. It is explicitly not recommended for the treatment of patients with type 1 diabetes mellitus. This is due to a significantly increased risk of diabetic ketoacidosis (DKA) in this population, a serious metabolic complication that can be life-threatening.[1]

Furthermore, its use is restricted in patients with significant renal impairment. Because the mechanism of action of bexagliflozin relies on glomerular filtration of glucose, its glycemic efficacy diminishes as renal function declines. It is not recommended for initiation in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2. The drug is contraindicated in patients with end-stage renal disease or those requiring dialysis, as it would be expected to have minimal efficacy and has not been studied in this population.[3]

Overview of the Clinical Development Program

The FDA approval of bexagliflozin was predicated on a robust and extensive clinical development program designed to rigorously evaluate its efficacy and safety. The program comprised 23 separate clinical trials that collectively enrolled more than 5,000 adult participants with T2DM from diverse backgrounds and with varying degrees of disease severity and comorbidities.[6] The trials were conducted at 428 sites across 16 countries, ensuring a broad and generalizable evidence base.[6]

The program included multiple Phase 3, adequate, and well-controlled investigations. These trials employed various designs, including placebo-controlled studies and active-controlled, non-inferiority studies.[3] Bexagliflozin was evaluated across a range of clinical scenarios: as a monotherapy for treatment-naïve patients, as an add-on therapy for patients inadequately controlled on metformin, and as an add-on to a wide array of standard-of-care background therapies in complex patient populations, including those with established cardiovascular disease or moderate renal impairment.[3]

Analysis of Pivotal Phase 3 Trials

The core evidence for bexagliflozin's efficacy comes from its pivotal Phase 3 trials, which consistently demonstrated its ability to improve glycemic control and other metabolic parameters.

Primary Efficacy Endpoint

Across the pivotal trials, the primary efficacy endpoint was the change from baseline in hemoglobin A1c (HbA1c) after a 24-week treatment period.[6] HbA1c is the gold-standard measure of long-term glycemic control and its reduction is a well-established surrogate for a lower risk of microvascular complications in diabetes.[3]

Efficacy as Monotherapy and Add-on Therapy

In placebo-controlled trials, bexagliflozin 20 mg once daily produced statistically significant and clinically meaningful reductions in HbA1c. As a monotherapy in treatment-naïve patients (Trial C-450) and as an add-on to metformin (Trial C-419), the placebo-adjusted mean reductions in HbA1c ranged from -0.38% to -0.48%.[3] Broader analyses of trial data show placebo-corrected HbA1c reductions ranging from 0.56% to 0.85% over treatment periods of 12 to 96 weeks.[34] These results were accompanied by significant reductions in fasting plasma glucose (FPG).[7] A meta-analysis of nine randomized controlled trials (RCTs) confirmed these findings, showing a standardized mean difference in HbA1c reduction of -0.55% versus placebo (p < 0.00001).[36]

The Bexagliflozin Efficacy and Safety Trial (BEST)

The landmark trial in the development program was the BEST trial (NCT02558296), a multinational, randomized, placebo-controlled cardiovascular outcomes trial (CVOT).[33] This study enrolled over 1,700 patients with T2DM who had either established atherosclerotic cardiovascular disease (CVD) or multiple risk factors for CVD.[33] The primary objectives were to assess both glycemic efficacy and cardiovascular safety.

• Glycemic Efficacy: At 24 weeks, the placebo-corrected mean change in HbA1c in the bexagliflozin group was a significant -0.48% (p < 0.0001).[37] This demonstrated robust glucose-lowering efficacy even in a complex, high-risk population on multiple background therapies.
• Cardiovascular Safety: The primary safety endpoint was a composite of major adverse cardiovascular events (MACE+), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for unstable angina. The trial was event-driven and designed to demonstrate non-inferiority to placebo. Bexagliflozin successfully met this objective, with a hazard ratio (HR) for MACE+ of 0.80 (95% Confidence Interval [CI] 0.58, 1.09), which fulfilled the pre-specified non-inferiority criterion (p < 0.0001).[37] This result established that bexagliflozin does not increase cardiovascular risk in this high-risk population.

Efficacy in Special Populations: Moderate Renal Impairment

A key differentiator for bexagliflozin emerged from a dedicated trial (C-448) in patients with T2DM and moderate chronic kidney disease (CKD), defined as an eGFR between 30 and <60 mL/min/1.73 m2.[3] This patient population is particularly challenging to treat, as the efficacy of many oral antidiabetic agents is reduced, and some, like metformin, may be contraindicated.[7] Despite the theoretical reduction in efficacy of SGLT2 inhibitors as GFR declines, bexagliflozin demonstrated a statistically significant placebo-corrected reduction in HbA1c of -0.37% over 24 weeks.[9] The effect was even more pronounced in the subgroup with Stage 3b CKD (eGFR 30 to <45 mL/min/1.73

m2), a finding of considerable clinical importance as therapeutic options are limited for these patients.[9] This demonstrates that bexagliflozin retains clinically meaningful glycemic efficacy at lower levels of renal function, positioning it as a valuable option for this high-need population.

Active Comparator Trials

In head-to-head, non-inferiority trials, bexagliflozin was compared against other commonly used oral antidiabetic agents. It was found to be non-inferior to the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin and the sulfonylurea glimepiride for HbA1c reduction.[36] Importantly, bexagliflozin was superior to both active comparators in producing reductions in body weight and systolic blood pressure, and it was associated with a significantly lower risk of hypoglycemia compared to glimepiride.[36] A Phase 3 trial conducted in Chinese patients also demonstrated that bexagliflozin 20 mg was non-inferior to dapagliflozin 10 mg as an add-on to metformin, with comparable efficacy and safety profiles.[39]

Ancillary Benefits

Consistent with the known class effects of SGLT2 inhibitors, the clinical trial program for bexagliflozin demonstrated several ancillary benefits beyond glycemic control.

• Body Weight Reduction: The induction of glycosuria results in a net caloric loss of up to 200-300 kcal per day, leading to a consistent reduction in body weight. In the BEST trial, patients with a baseline BMI ≥25 kg/m2 experienced a placebo-corrected mean weight loss of 2.65 kg at 48 weeks (p < 0.0001).[34] A 96-week monotherapy trial showed that this weight loss was sustained over the long term.[34]
• Blood Pressure Reduction: The mild osmotic diuresis and natriuresis induced by SGLT2 inhibition contribute to a modest but clinically significant reduction in blood pressure. In the BEST trial, participants with a baseline systolic blood pressure (SBP) ≥140 mmHg had a placebo-corrected SBP reduction of 2.96 mmHg at 24 weeks (p = 0.012).[34] This effect is beneficial for the many patients with T2DM who also have comorbid hypertension.

Table 3: Summary of Key Phase 3 Clinical Trial Efficacy Outcomes

Trial Identifier / Population	Comparator	Duration	Mean Baseline HbA1c (%)	Placebo-Corrected Change in HbA1c (%)	Placebo-Corrected Change in Body Weight (kg)	Placebo-Corrected Change in SBP (mmHg)	Source(s)
BEST (NCT02558296) T2DM with High CV Risk	Placebo	24 weeks	8.3	-0.48	-2.65 (at 48 wks)	-2.96 (in hypertensive pts)	34
Monotherapy (NCT02715258) T2DM, Treatment-Naïve	Placebo	24 weeks	8.0	-0.57*	-1.82*	-2.5*	3
Add-on to Metformin (NCT03259789) T2DM on Metformin	Placebo	24 weeks	8.6	-0.53	-2.25*	-4.4*	39
Renal Impairment (C-448) T2DM with Stage 3 CKD	Placebo	24 weeks	7.9	-0.37	-1.5*	-2.9*	3
Active Comparator T2DM on Metformin	Glimepiride	96 weeks	8.0	Non-inferior	Superior Reduction	Superior Reduction	36
Active Comparator T2DM on Metformin	Sitagliptin	24 weeks	7.9	Non-inferior	Superior Reduction	Not Reported	36

Note: Values marked with an asterisk () represent mean differences from placebo derived from various trial publications and meta-analyses and may have different timepoints or patient subgroups than the BEST trial data. Non-inferiority indicates that bexagliflozin was not worse than the active comparator by a pre-specified margin.*

Safety, Tolerability, and Risk Management

A thorough understanding of a drug's safety profile is paramount for its appropriate and safe clinical application. The safety of bexagliflozin has been extensively characterized through its clinical development program, revealing a profile that is largely consistent with the SGLT2 inhibitor class, including both common, manageable side effects and rare but serious risks that require careful monitoring and patient education.

Adverse Event Profile

Most Common Adverse Reactions

The most frequently reported adverse reactions in clinical trials (occurring in >5% of patients) are directly related to the drug's mechanism of action, which increases glucose in the genitourinary tract. These include:

• Female Genital Mycotic Infections: (e.g., vulvovaginal candidiasis).[15]
• Urinary Tract Infections (UTIs):.[15]
• Increased Urination: (including pollakiuria, polyuria, and nocturia).[15]

These events are typically mild to moderate in severity and can often be managed with standard therapies without necessitating discontinuation of the drug. In the large BEST trial, the overall rate of adverse events leading to treatment discontinuation was nearly identical between the bexagliflozin and placebo arms (8.4% vs. 8.5%, respectively), indicating good overall tolerability.[37]

Warnings and Precautions (In-depth Analysis)

The prescribing information for bexagliflozin includes several important warnings and precautions that reflect serious risks identified with the SGLT2 inhibitor class.

Diabetic Ketoacidosis (DKA)

Bexagliflozin, like all SGLT2 inhibitors, is associated with a risk of DKA, a life-threatening metabolic emergency characterized by ketoacidosis and hyperglycemia.[1] The risk is substantially elevated in patients with type 1 diabetes, for whom the drug is not approved.[29] However, DKA has also been reported in patients with T2DM, particularly in the context of precipitating factors such as acute febrile illness, surgery, prolonged fasting, reduced caloric or fluid intake, excessive alcohol consumption, or a reduction in insulin dosage.[15] A critical diagnostic challenge is that SGLT2 inhibitor-associated DKA can present with only moderately elevated or even normal blood glucose levels (euglycemic DKA), often below 250 mg/dL.[7] This atypical presentation can delay diagnosis and treatment. Patients should be educated on the signs and symptoms of DKA (nausea, vomiting, abdominal pain, fatigue, shortness of breath) and advised to seek immediate medical attention if they occur. Therapy should be temporarily withheld prior to scheduled surgery or during acute medical illnesses.[29]

Lower Limb Amputation

An increased incidence of lower limb amputations (primarily of the toe and midfoot) has been observed with some SGLT2 inhibitors. In the BEST trial, which enrolled a high-risk cardiovascular population, the incidence of amputation was higher in the bexagliflozin group compared to placebo (8.3 vs. 5.1 events per 1000 patient-years).[1] The events were often preceded by lower limb infections, gangrene, or diabetic foot ulcers.[15] The risk is not uniform across all patients; it is highest in those with a pre-existing history of prior amputation, peripheral vascular disease, or neuropathy.[7] This finding does not represent a blanket contraindication but rather a strong mandate for careful patient selection and proactive risk mitigation. Before initiating bexagliflozin, clinicians must perform a thorough risk assessment. All patients, especially those at high risk, should be counseled on the critical importance of routine, preventative foot care and should be monitored for any new pain, tenderness, sores, ulcers, or signs of infection in the lower limbs. If such complications arise, bexagliflozin should be discontinued promptly.[7]

Volume Depletion

The osmotic diuretic effect of bexagliflozin can lead to intravascular volume contraction, which may manifest as symptomatic hypotension or acute transient changes in serum creatinine.[1] Postmarketing reports for the SGLT2 inhibitor class include cases of acute kidney injury, some requiring hospitalization and dialysis.[15] The risk of volume depletion is heightened in certain populations, including elderly patients, those with pre-existing renal impairment (eGFR <60 mL/min/1.73

m2), patients with low baseline systolic blood pressure, and those receiving concomitant diuretic therapy, particularly loop diuretics.[15] In these at-risk patients, volume status should be assessed and corrected, if necessary, before initiating therapy. Close monitoring of volume status (e.g., blood pressure) and renal function is recommended after initiation.[29]

Urosepsis and Pyelonephritis

While UTIs are a common adverse event, serious and life-threatening infections, including urosepsis and pyelonephritis requiring hospitalization, have been reported in patients receiving SGLT2 inhibitors.[1] Clinicians should evaluate patients for signs and symptoms of urinary tract infection and institute prompt treatment when indicated.[29]

Necrotizing Fasciitis of the Perineum (Fournier's Gangrene)

Fournier's gangrene is a rare but extremely serious and life-threatening necrotizing infection of the perineal, genital, or perianal tissues that has been reported in postmarketing surveillance for the SGLT2 inhibitor class.[6] It requires immediate, aggressive surgical debridement and broad-spectrum antibiotic therapy. Patients should be advised to seek immediate medical attention if they experience pain, tenderness, erythema, or swelling in the genital or perineal area, accompanied by fever or malaise.[30] If Fournier's gangrene is suspected, bexagliflozin must be discontinued immediately.[15]

Hypoglycemia

When used as monotherapy, bexagliflozin carries a very low risk of hypoglycemia because its mechanism does not actively drive glucose levels below the normal range.[5] However, when bexagliflozin is used in combination with insulin or insulin secretagogues (e.g., sulfonylureas, meglitinides), which independently increase insulin levels, the risk of hypoglycemia is substantially increased due to a pharmacodynamic synergistic effect.[1] To mitigate this risk, a proactive reduction in the dose of the concomitant insulin or insulin secretagogue may be necessary upon initiation of bexagliflozin.[29]

Genital Mycotic Infections

The glycosuria induced by bexagliflozin creates a favorable environment for the growth of yeast, leading to an increased risk of genital mycotic infections.[1] These infections are more common in women (vulvovaginal candidiasis) and in uncircumcised men (balanitis or balanoposthitis).[30] Patients with a prior history of such infections are also at higher risk.[15] Patients should be counseled on the signs and symptoms and advised on appropriate hygiene and treatment options.[30]

Contraindications

Bexagliflozin is contraindicated in the following patient populations:

• Patients with a history of a serious hypersensitivity reaction, such as anaphylaxis or angioedema, to bexagliflozin or any of its excipients.[30]
• Patients on dialysis.[5]

Use in Specific Populations

• Renal Impairment: Efficacy is reduced in patients with renal impairment. Bexagliflozin is not recommended for patients with an eGFR <30 mL/min/1.73 m2. Patients with renal impairment also have a higher incidence of renal-related adverse reactions.[15]
• Hepatic Impairment: While no dose adjustment is needed for mild to moderate hepatic impairment, bexagliflozin has not been studied in patients with severe hepatic impairment and is therefore not recommended for use in this population.[15]
• Pregnancy and Lactation: Due to potential risks to the developing fetus, particularly renal development, bexagliflozin is not recommended during the second and third trimesters of pregnancy. Because the drug is excreted in the milk of lactating rats, it is presumed to be present in human milk, and breastfeeding is not recommended during treatment.[15]

Drug Interactions

Pharmacokinetic Interactions

• UGT Enzyme Inducers: Bexagliflozin is a major substrate of the UGT1A9 enzyme. Concomitant administration with potent UGT inducers (e.g., rifampin, phenytoin, phenobarbital) may significantly increase the metabolism of bexagliflozin, leading to reduced systemic exposure and decreased glycemic efficacy. If co-administration is necessary, clinicians should consider adding another antihyperglycemic agent to maintain glycemic control.[27]

Pharmacodynamic Interactions

• Insulin and Insulin Secretagogues: As previously discussed, co-administration significantly increases the risk of hypoglycemia. A lower dose of the insulin or secretagogue is often required.[27]
• Lithium: SGLT2 inhibitors can increase the urinary excretion of lithium, potentially leading to subtherapeutic serum lithium concentrations. More frequent monitoring of serum lithium levels is recommended upon initiation, dose change, or discontinuation of bexagliflozin.[27]
• Diuretics: The concurrent use of diuretics, especially loop diuretics, can potentiate the volume-depleting effects of bexagliflozin, increasing the risk of dehydration and hypotension.[15]

Laboratory Test Interference

• Urine Glucose Tests: Due to its mechanism of action, bexagliflozin will cause all patients to have a positive urine glucose test. This test is therefore not a reliable method for monitoring glycemic control in patients taking the drug.[29]
• 1,5-Anhydroglucitol (1,5-AG) Assay: The 1,5-AG assay is also rendered unreliable for assessing glycemic control in patients on SGLT2 inhibitors. Alternative methods, such as self-monitoring of blood glucose and HbA1c testing, must be used.[31]

Table 4: Clinically Significant Drug Interactions with Bexagliflozin

Interacting Drug/Class	Mechanism of Interaction	Clinical Impact	Management Recommendation	Source(s)
UGT Enzyme Inducers (e.g., rifampin, phenytoin)	Increased metabolism of bexagliflozin via UGT1A9 induction	Reduced systemic exposure and decreased efficacy of bexagliflozin	Consider adding another antihyperglycemic agent if additional glycemic control is required.	27
Insulin and Insulin Secretagogues (e.g., sulfonylureas)	Pharmacodynamic synergism	Increased risk of hypoglycemia	A lower dose of insulin or the insulin secretagogue may be required. Monitor blood glucose closely.	27
Lithium	Increased renal clearance of lithium	Decreased serum lithium concentrations, potentially leading to loss of efficacy	Monitor serum lithium concentrations more frequently upon initiation, dose change, or discontinuation of bexagliflozin.	27
Diuretics (especially loop diuretics)	Additive diuretic effect	Increased risk of intravascular volume depletion, hypotension, and acute kidney injury	Assess and correct volume status before initiation. Monitor for signs and symptoms of volume depletion.	15

Regulatory and Commercial Landscape

Regulatory History and Approval

Bexagliflozin was developed by TheracosBio, LLC, a pharmaceutical company based in Marlborough, Massachusetts.[3] Following the successful completion of its extensive clinical trial program, the company submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration. The FDA granted its first approval for bexagliflozin on January 20, 2023, with the public announcement following on January 23, 2023.[4] This approval marked the introduction of the fifth oral SGLT2 inhibitor for the treatment of T2DM in the United States.[5] The drug is also undergoing clinical development for the treatment of essential hypertension.[45]

Brand Information and Market Strategy

Human Brand Name and Formulation

For human use, bexagliflozin is marketed under the brand name Brenzavvy™.[1] It is available as a 20 mg, blue, caplet-shaped, biconvex tablet.[31]

Commercial and Pricing Strategy

The commercial strategy adopted by TheracosBio for Brenzavvy™ represents a significant departure from the conventional pricing models for new, branded pharmaceuticals in the United States. The company has publicly committed to a strategy focused on transparent and affordable pricing, aiming to broaden patient access to the SGLT2 inhibitor class.[8] The stated cash price for patients is approximately $50 per month, a fraction of the list price of other branded agents in the class.[46] To execute this strategy, TheracosBio has formed a key partnership with the Mark Cuban Cost Plus Drug Company and next-generation pharmacy benefits managers (PBMs) like SmithRx.[8]

This approach directly confronts the significant cost-related barriers that often prevent patients from accessing newer, more effective diabetes medications. The high cost of novel antidiabetic drugs is a major driver of non-adherence, which in turn leads to poor health outcomes. By offering a lower-cost alternative, Brenzavvy™ is positioned not only as a clinical option but also as a pharmacoeconomic one. This strategy could be a powerful market disruptor, potentially influencing prescribing decisions based on patient affordability and improving medication adherence and, by extension, overall public health outcomes.

Unique Veterinary Application

In a highly unusual and noteworthy development, bexagliflozin has also received FDA approval for veterinary use.

• Veterinary Brand Name: Bexacat™.[6]
• Indication: For improving glycemic control in otherwise healthy cats with diabetes mellitus that have not previously been treated with insulin.[6]
• Significance: Bexacat™ is the first-ever SGLT2 inhibitor to be approved by the FDA for use in any animal species.[6]

This dual approval for both human and feline diabetes is a testament to the drug's well-characterized safety profile and the conserved nature of the SGLT2 mechanism across species. It suggests a broad therapeutic index and a robust preclinical and clinical data package that satisfied the stringent safety and efficacy requirements for two distinct regulatory pathways. This unique status further distinguishes bexagliflozin within the pharmaceutical landscape.

Expert Synthesis and Concluding Remarks

Integrated Risk-Benefit Assessment

Bexagliflozin (Brenzavvy™) has demonstrated a positive risk-benefit profile for its approved indication of improving glycemic control in adults with type 2 diabetes mellitus. The evidence from a comprehensive clinical development program establishes its robust efficacy, with clinically meaningful reductions in HbA1c and fasting plasma glucose, both as monotherapy and as an add-on to other antidiabetic agents. This glycemic efficacy is complemented by valuable ancillary benefits, including consistent and sustained reductions in body weight and systolic blood pressure, which address common comorbidities in the T2DM population. A particularly compelling aspect of its profile is its demonstrated efficacy in patients with moderate chronic kidney disease (Stage 3b), a population with limited therapeutic options.

These benefits must be carefully weighed against the known risks associated with the SGLT2 inhibitor class. Serious warnings, including the potential for euglycemic diabetic ketoacidosis, an increased incidence of lower limb amputations in high-risk populations, necrotizing fasciitis of the perineum (Fournier's gangrene), and serious urinary tract infections, demand rigorous patient selection, ongoing monitoring, and comprehensive patient education. More common adverse events, such as genital mycotic infections, are generally manageable but require counseling. For the appropriately selected patient who is well-informed and monitored, the benefits of improved glycemic control, weight loss, and blood pressure reduction offered by bexagliflozin are substantial and generally outweigh the potential risks.

Comparative Analysis and Place in Therapy

As the fifth oral SGLT2 inhibitor to market, bexagliflozin's place in therapy is defined by its relative strengths and weaknesses compared to established agents like empagliflozin, canagliflozin, and dapagliflozin. In terms of core glycemic efficacy, bexagliflozin appears largely comparable to its predecessors. Head-to-head trial data against dapagliflozin showed non-inferiority, and its magnitude of HbA1c reduction in placebo-controlled trials is in line with the established class effect.[34] While its dedicated cardiovascular outcomes trial (BEST) successfully demonstrated non-inferiority for MACE, it was not powered to show superiority, unlike the landmark trials for some of its competitors that led to broad indications for cardiovascular risk reduction.

However, bexagliflozin possesses two key potential differentiators that may carve out a significant niche for it in clinical practice. First is its proven efficacy in patients with Stage 3b CKD (eGFR 30 to <45 mL/min/1.73 m2).[9] This provides clinicians with an evidence-based option for a difficult-to-treat population where other agents may be less effective or contraindicated. Second, and perhaps most impactful, is its disruptive pricing and market access strategy.[8] By offering a transparent, low-cost option, Brenzavvy™ directly addresses the pervasive issue of medication affordability, which is a major barrier to care. This could make it a preferred agent for patients who are uninsured, underinsured, or facing high co-pays, thereby improving access to the benefits of the SGLT2 inhibitor class for a wider population.

Therefore, the place in therapy for bexagliflozin is as a safe and effective SGLT2 inhibitor with particular value in patients with moderate renal impairment and in any patient for whom cost is a significant consideration.

Recommendations for Clinical Practice

Based on the available evidence, the following recommendations are provided for clinicians considering the use of bexagliflozin:

1. Patient Selection is Critical: Conduct a thorough baseline assessment. Bexagliflozin is an appropriate choice for many adults with T2DM, but carefully evaluate risk factors for amputation (history of amputation, peripheral vascular disease, neuropathy) and DKA (pancreatic insufficiency, history of pancreatitis, ketogenic diet, alcohol abuse). Use with caution in these high-risk individuals and ensure robust preventative care measures are in place.
2. Baseline and Ongoing Monitoring: Before initiation, assess renal function (eGFR) and volume status. Correct any existing volume depletion. Do not initiate if eGFR is <30 mL/min/1.73 m2. Monitor renal function and volume status periodically during treatment, especially in at-risk patients (elderly, those on diuretics).
3. Proactive Management of Concomitant Medications: When initiating bexagliflozin in a patient already taking insulin or an insulin secretagogue, consider a pre-emptive dose reduction of the latter to mitigate the risk of hypoglycemia. If a patient is on lithium, plan for more frequent monitoring of serum levels. Be aware of potent UGT inducers, which may reduce bexagliflozin's efficacy.
4. Comprehensive Patient Counseling: Education is a cornerstone of safe use. Counsel patients on:

• Foot Care: The importance of daily self-inspections and reporting any new sores, ulcers, pain, or signs of infection immediately.
• DKA Symptoms: The signs of DKA (nausea, vomiting, abdominal pain, shortness of breath) and the need to seek immediate medical help, emphasizing that it can occur even with normal blood sugar.
• Genitourinary Health: The symptoms of genital mycotic infections and UTIs and the importance of good hygiene and prompt treatment.
• Hydration: The need to maintain adequate fluid intake to prevent volume depletion and hypotension.
• Sick Day Rules: When to temporarily stop the medication, such as during acute illness, prolonged fasting, or before major surgery.

Future Directions

While the current data for bexagliflozin is robust, several areas warrant further investigation. Although it has shown efficacy in moderate CKD, long-term, large-scale studies are needed to definitively establish its renoprotective effects (i.e., slowing the progression of CKD and reducing the risk of end-stage renal disease) to the same extent as has been demonstrated for other agents in the class.[34] The ongoing clinical development for essential hypertension is a promising avenue that could expand its therapeutic utility beyond diabetes.[45] Finally, as real-world evidence accumulates, a clearer picture of its effectiveness and safety across diverse, unselected patient populations will emerge, further refining its optimal place in the complex and evolving landscape of diabetes and cardio-renal-metabolic medicine.

Works cited

1. Bexagliflozin: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed August 28, 2025, https://go.drugbank.com/drugs/DB12236
2. Bexagliflozin (EGT1442) | 99.73%(HPLC) | In Stock | SGLT inhibitor - Selleck Chemicals, accessed August 28, 2025, https://www.selleckchem.com/products/bexgliflozin-egt1442.html
3. 214373Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov, accessed August 28, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/214373Orig1s000IntegratedR.pdf
4. Brenzavvy (bexagliflozin) FDA Approval History - Drugs.com, accessed August 28, 2025, https://www.drugs.com/history/brenzavvy.html
5. Bexagliflozin as an Adjunct Therapy to Diet and Exercise to Improve Glycaemic Control in Adults with Type 2 Diabetes - PMC, accessed August 28, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11132653/
6. Bexagliflozin - Wikipedia, accessed August 28, 2025, https://en.wikipedia.org/wiki/Bexagliflozin
7. TheracosBio Announces FDA Approval of Brenzavvy ..., accessed August 28, 2025, https://theracosbio.com/wp-content/uploads/2023/01/01-23-2023_TheracosBio-Announces-FDA-Approval-of-Brenzavvy.pdf
8. TheracosBio and SmithRx Collaborate to Offer Newly Approved Diabetes Drug Brenzavvy™ (bexagliflozin) to Members with Type 2 Diabetes - BioSpace, accessed August 28, 2025, https://www.biospace.com/theracosbio-and-smithrx-collaborate-to-offer-newly-approved-diabetes-drug-brenzavvy-bexagliflozin-to-members-with-type-2-diabetes
9. New FDA-approved SGLT2 Inhibitor Bexagliflozin for Type 2 ..., accessed August 28, 2025, https://discoveriesjournals.org/discoveries-reports/DRep.2023.PA-Dindere.pdf
10. Bexagliflozin: Comprehensive pharmacological profile and clinical applications in type 2 diabetes, accessed August 28, 2025, https://jmnc.samipubco.com/article_212952_6e61689c7035897d23c7ab7659c62299.pdf
11. Full article: Metabolism and disposition of the SGLT2 inhibitor bexagliflozin in rats, monkeys and humans - Taylor & Francis Online, accessed August 28, 2025, https://www.tandfonline.com/doi/full/10.1080/00498254.2019.1654634
12. Bexagliflozin – evaluation of the clinical efficacy, safety profile and potential new applications of the SGLT2 inhibitor, accessed August 28, 2025, https://jms.ump.edu.pl/index.php/JMS/article/download/1226/1169/9243
13. Bexagliflozin | C24H29ClO7 | CID 25195624 - PubChem, accessed August 28, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/Bexagliflozin
14. diabetesjournals.org, accessed August 28, 2025, https://diabetesjournals.org/clinical/article/42/1/169/153794/Bexagliflozin#:~:text=Mechanism%20of%20Action,-SGLT2%20is%20responsible&text=SGLT2%20inhibitors%20such%20as%20bexagliflozin,requiring%20insulin%20secretion%20(5).
15. CV Safety Profile of TheracosBio's BRENZAVVY® (bexagliflozin) Confirmed in Research Published in Diabetes, accessed August 28, 2025, https://theracosbio.com/wp-content/uploads/2024/01/TheracoBio_CV_Safety_Press_Release_20240107_FINAL.pdf
16. bexagliflozin | Ligand page - IUPHAR/BPS Guide to PHARMACOLOGY, accessed August 28, 2025, https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=12335
17. bexagliflozin | Ligand page - IUPHAR/BPS Guide to PHARMACOLOGY, accessed August 28, 2025, https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=structure&ligandId=12335
18. bexagliflozin | Ligand page - IUPHAR/BPS Guide to PHARMACOLOGY, accessed August 28, 2025, https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=12335
19. [Table, CHEMICAL FORMULAS AND STRUCTURES]. - LiverTox - NCBI Bookshelf, accessed August 28, 2025, https://www.ncbi.nlm.nih.gov/books/NBK548289/table/SGLT-2_Inhibitors.Tc/
20. Bexagliflozin | EGT-1442 | THR144 | CAS#1118567-05-7 | MedKoo Biosciences, accessed August 28, 2025, https://www.medkoo.com/products/6716
21. Bexagliflozin | 1118567-05-7 - ChemicalBook, accessed August 28, 2025, https://www.chemicalbook.com/ChemicalProductProperty_EN_CB92650633.htm
22. Formulation development and evaluation of Bexagliflozin loaded nano emulsion | Library Progress International - BPAS Journals, accessed August 28, 2025, https://bpasjournals.com/library-science/index.php/journal/article/download/2884/2704/5850
23. Bexagliflozin | CAS NO.:1118567-05-7 | GlpBio, accessed August 28, 2025, https://www.glpbio.com/kr/bexagliflozin.html
24. Compound: BEXAGLIFLOZIN (CHEMBL1808388) - ChEMBL - EMBL-EBI, accessed August 28, 2025, https://www.ebi.ac.uk/chembl/explore/compound/CHEMBL1808388
25. 1118567-05-7 | MFCD28100944 | Bexagliflozin | AA Blocks, accessed August 28, 2025, https://www.aablocks.com/prod/1118567-05-7
26. Bexagliflozin | 1118567-05-7 | FA145137 - Biosynth, accessed August 28, 2025, https://www.biosynth.com/p/FA145137/1118567-05-7-bexagliflozin
27. Brenzavvy (bexagliflozin) dosing, indications, interactions, adverse effects, and more, accessed August 28, 2025, https://reference.medscape.com/drug/brenzavvy-bexagliflozin-4000358
28. BEXAGLIFLOZIN - Inxight Drugs, accessed August 28, 2025, https://drugs.ncats.io/drug/EY00JF42FV
29. Bexagliflozin Monograph for Professionals - Drugs.com, accessed August 28, 2025, https://www.drugs.com/monograph/bexagliflozin.html
30. Bexagliflozin Dosage Guide + Max Dose, Adjustments - Drugs.com, accessed August 28, 2025, https://www.drugs.com/dosage/bexagliflozin.html
31. BRENZAVVY- bexagliflozin tablet - DailyMed, accessed August 28, 2025, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3cdf28fc-4194-4ad6-aa03-c9eaa68da83e
32. Bexagliflozin: MedlinePlus Drug Information, accessed August 28, 2025, https://medlineplus.gov/druginfo/meds/a623027.html
33. Study Details | Bexagliflozin Efficacy and Safety Trial - ClinicalTrials.gov, accessed August 28, 2025, https://clinicaltrials.gov/study/NCT02558296
34. Bexagliflozin | Clinical Diabetes, accessed August 28, 2025, https://diabetesjournals.org/clinical/article/42/1/169/153794/Bexagliflozin
35. FDA approves new type 2 diabetes drug bexagliflozin | MDedge, accessed August 28, 2025, https://ma1.mdedge.com/content/fda-approves-new-type-2-diabetes-drug-bexagliflozin
36. Efficacy and Safety of Bexagliflozin, a Selective Sodium-Glucose ..., accessed August 28, 2025, https://journals.viamedica.pl/clinical_diabetology/article/view/104462
37. Best: Bexagliflozin Led to Significant Reductions in HBA1C and ..., accessed August 28, 2025, https://www.ccjm.org/page/ada-2020/bexagliflozin
38. (PDF) Meta‐analysis of risk of major adverse cardiovascular events in adults with type 2 diabetes treated with bexagliflozin - ResearchGate, accessed August 28, 2025, https://www.researchgate.net/publication/377079863_Meta-analysis_of_risk_of_major_adverse_cardiovascular_events_in_adults_with_type_2_diabetes_treated_with_bexagliflozin
39. Efficacy and safety of bexagliflozin compared with dapagliflozin as an adjunct to metformin in Chinese patients with type 2 diabetes mellitus: A 24‐week, randomized, double‐blind, active‐controlled, phase 3 trial - PubMed Central, accessed August 28, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10999497/
40. Safety and Efficacy of Bexagliflozin as Monotherapy in Patients With Type 2 Diabetes, accessed August 28, 2025, https://clinicaltrials.gov/study/NCT02715258
41. Safety and Efficacy of Bexagliflozin Compared to Placebo as Add-on Therapy to Metformin in Type 2 Diabetes Subjects | ClinicalTrials.gov, accessed August 28, 2025, https://clinicaltrials.gov/study/NCT03259789
42. Bexagliflozin | Memorial Sloan Kettering Cancer Center, accessed August 28, 2025, https://www.mskcc.org/pdf/cancer-care/patient-education/medications/adult/bexagliflozin
43. FDA approves new medication for type 2 diabetes - Cardiovascular Business, accessed August 28, 2025, https://cardiovascularbusiness.com/topics/clinical/pharmaceutics/fda-approves-new-medication-type-2-diabetes
44. Bexagliflozin (oral route) - Side effects & dosage - Mayo Clinic, accessed August 28, 2025, https://www.mayoclinic.org/drugs-supplements/bexagliflozin-oral-route/description/drg-20544720
45. Bexagliflozin: First Approval - PubMed, accessed August 28, 2025, https://pubmed.ncbi.nlm.nih.gov/36867399/
46. Brenzavvy: For Patients, accessed August 28, 2025, https://brenzavvy.com/