Canagliflozin
[CAS# 842133-18-0]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs >> Pancreatic hormones and other blood sugar regulating drugs
• Name: Canagliflozin
• Synonyms: (1S)-1,5-Anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol
• Molecular Formula: C₂₄H₂₅FO₅S
• Molecular Weight: 444.52
• CAS Registry Number: 842133-18-0
• EC Number: 695-192-1
• SMILES: CC1=C(C=C(C=C1)[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)O)O)CC3=CC=C(S3)C4=CC=C(C=C4)F

Properties

• Density: 1.364

Safety Data

• Hazard Symbols: GHS05;GHS07;GHS08;GHS09 Danger
• Hazard Statements: H302-H318-H319-H361-H362-H411
• Precautionary Statements: P203-P260-P263-P264-P264+P265-P270-P273-P280-P301+P317-P305+P351+P338-P305+P354+P338-P317-P318-P330-P337+P317-P391-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Reproductive toxicity	Repr.	2	H361
Reproductive toxicity	Lact.	-	H362
Serious eye damage	Eye Dam.	1	H318
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H302

Discovory and Applicatios

Canagliflozin is an oral medication used primarily to manage type 2 diabetes. It belongs to a class of drugs known as sodium-glucose co-transporter-2 (SGLT2) inhibitors, which help lower blood sugar levels by promoting the excretion of glucose through urine. Discovered and developed in the early 2000s, canagliflozin represents a significant advancement in diabetes treatment, offering a novel mechanism of action that complements other diabetes therapies.

The discovery of canagliflozin was part of the broader search for new antidiabetic drugs that could address the limitations of existing treatments. Traditional medications like insulin and sulfonylureas focus on increasing insulin levels or improving insulin sensitivity. However, they do not directly reduce glucose reabsorption in the kidneys, which plays a critical role in maintaining high blood sugar levels in diabetic patients. Canagliflozin was designed to inhibit SGLT2, a protein responsible for reabsorbing the majority of glucose filtered by the kidneys. By blocking SGLT2, canagliflozin reduces glucose reabsorption, leading to increased glucose excretion and, consequently, lower blood sugar levels.

Canagliflozin was approved by the U.S. Food and Drug Administration (FDA) in 2013 as the first SGLT2 inhibitor for the treatment of type 2 diabetes. Its approval was based on clinical trials demonstrating its effectiveness in lowering glycated hemoglobin (HbA1c) levels, which are a key marker of long-term blood sugar control. Additionally, canagliflozin was found to aid in weight loss and reduce blood pressure, offering further benefits to patients with type 2 diabetes, who often struggle with obesity and hypertension.

One of the unique aspects of canagliflozin is its dual action in managing diabetes and reducing cardiovascular risks. Studies have shown that canagliflozin not only improves glycemic control but also lowers the risk of major cardiovascular events, such as heart attacks and strokes, in patients with type 2 diabetes. This has made canagliflozin an attractive option for patients at high cardiovascular risk, providing a twofold benefit in diabetes management.

Canagliflozin is typically administered as a once-daily oral tablet, making it convenient for patients to incorporate into their daily routine. It is often used in combination with other antidiabetic medications, such as metformin, to achieve better blood sugar control. The dosage of canagliflozin may be adjusted based on the patient’s kidney function and overall health status.

However, like all medications, canagliflozin is not without its risks. Common side effects include urinary tract infections and genital yeast infections, which occur due to the increased glucose in the urine. More serious concerns include an increased risk of diabetic ketoacidosis (a potentially life-threatening condition) and lower limb amputations, particularly in patients with a history of vascular disease or neuropathy. These risks necessitate careful patient selection and monitoring during treatment.

Despite these concerns, canagliflozin remains an important tool in the management of type 2 diabetes, particularly for patients who need additional blood sugar control beyond what is achievable with other medications. Its introduction has expanded the therapeutic options available to diabetic patients, providing a means to manage blood sugar levels while also offering cardiovascular protection.