canagliflozin/metformin

Action and Spectrum

Actions and Spectrum 

canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor. It works by inhibiting the reabsorption of glucose in the kidneys, leading to increased urinary glucose excretion. 

metformin belongs to the biguanide class of medications. It functions by reducing the liver’s capacity to produce glucose and increased the tissues sensitivity to insulin. canagliflozin/metformin both are used for the management of type 2 diabetes mellitus.

Drug Interaction

Adverse Reaction

Frequency defined  

1-10% 

For canagliflozin 

Increased urination (4.6-5.3%) 

Thirst (2.3-2.8%) 

Constipation (1.8-2.3%) 

Abdominal pain (1.7-1.8%) 

Male genital mycotic infections (3.7-4.2%) 

Bone fractures (1.1-1.5%) 

Nausea (2.2-2.3%) 

Vulvovaginal pruritus (1.6-3%) 

Falls (1.3-2.1%) 

Use of loop diuretic (3.2-8.8%) 

For metformin 

Asthenia (9.2%) 

Headache (5.7%) 

Indigestion (7.1%) 

Abdominal discomfort (6.4%) 

>10% 

For canagliflozin 

Female genital mycotic infections (10.4-11.4%) 

For metformin 

Nausea or vomiting (25.5%) 

Flatulence (12.1%) 

Diarrhea (53.2%) 

Post marketing Reports 

Angioedema 

For canagliflozin 

Acute kidney injury and impairment in renal function 

For metformin 

Anaphylaxis 

Urosepsis and Pyelonephritis 

Cholestatic, mixed hepatocellular liver injury and hepatocellular 

Black Box Warning

Black Box Warning 

metformin-associated lactic acidosis cases that occurred after the drug’s release have led to fatalities, hypothermia, hypotension, and resistant bradyarrhythmias.   

Renal impairment, concurrent use of certain medicines, age 65 or higher, having a radiological study with contrast, and surgery are risk factors for metformin-associated lactic acidosis. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Anaphylaxis or angioedema-related history of a significant hypersensitivity reaction to canagliflozin/metformin. 

Caution: 

• Caution should be taken in patients with an increased risk of hypotension. 
• canagliflozin/metformin should be discontinued if diabetic ketoacidosis is suspected. 
• The combination medication should be used with caution in patients with hepatic impairment. 
• canagliflozin/metformin should be used with caution in patients with mild to moderate renal impairment. 

Pregnancy / Lactation

Pregnancy consideration: 

Pregnancy category: N/A 

Lactation: Excretion into human milk is unknown  

Pregnancy Categories:         

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.  

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women. 

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 

Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology  

The sodium-glucose co-transporter 2 (SGLT2) in the kidneys is specifically inhibited by the drug canagliflozin. By inhibiting SGLT2, it decreases renal glucose reabsorption and boosts urine glucose excretion. Blood glucose levels drop as a result of this mechanism. 

metformin inhibits mitochondrial glycerophosphate dehydrogenase, which is the main mechanism by which it lowers hepatic gluconeogenesis. It also increases insulin sensitivity in peripheral tissue. 

Pharmacodynamics 

canagliflozin reduces plasma glucose levels by increasing urinary glucose excretion. 

metformin decreases fasting plasma glucose levels and postprandial hyperglycemia, and it will help to improve glycemic control. 

Pharmacokinetics 

Absorption   

canagliflozin/metformin both are well absorbed after oral administration. 

Distribution 

canagliflozin has a high plasma protein binding of approximately 99%. It has a steady-state volume of distribution of approximately 119 L. 

metformin is not extensively bound to plasma proteins and has a steady-state volume of distribution of approximately 654 L. 

Metabolism 

canagliflozin undergoes metabolism in the liver primarily through UGT1A9.  

metformin is not extensively metabolized in the liver.  

Elimination and excretion 

canagliflozin is eliminated unchanged in the urine, with approximately 33% excreted as active metabolites.  

metformin is eliminated unchanged in the urine through active tubular secretion.

Adminstartion

Administration 

canagliflozin/metformin is available in tablet form, and it’s administered through orally. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: canagliflozin/metformin 

Why do we use canagliflozin/metformin? 

canagliflozin/metformin is indicated as a supplement to diet and exercise to improve glycemic control in adults with Type 2 diabetes.  

canagliflozin inhibits the reabsorption of glucose in the kidneys, leading to increased urinary glucose excretion.  

metformin reduces hepatic glucose production and improves insulin sensitivity in peripheral tissues.