saxagliptin/metformin

Action and Spectrum

Actions and Spectrum: 

saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitors. It works by inhibiting the enzyme DPP-4. As a result, it breaks down incretin hormones such as glucagon-like peptide-1 (GLP-1). By inhibiting DPP-4, saxagliptin increases the levels of GLP-1 in the body, stimulating insulin secretion and reducing glucagon release. This helps to lower blood glucose levels. 

Spectrum 

saxagliptin primarily targets the regulation of postprandial (after-meal) blood glucose levels. It helps to control the rise in blood sugar levels after a meal by increasing insulin release and reducing glucagon secretion. 

metformin has a broader spectrum of action compared to saxagliptin. It mainly targets fasting blood glucose levels, which are elevated due to increased hepatic glucose production. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Diarrhea (9.6%) 

Hypoglycemia, saxagliptin (1.6%) 

Nausea/vomiting (6.5%) 

Headache (6.5%) 

<1% 

Lymphopenia 

Rash 

Black Box Warning

Black Box Warning: 

Accumulation of metformin can cause lactic acidosis. Immediately discontinue the therapy in this case. 

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• Hypersensitivity 

Cautions 

• Renal impairment 
• Hepatic impairment 
• Lactic acidosis 
• Hypoglycemia 
• Drug interactions 

Pregnancy / Lactation

Pregnancy consideration:  

Insufficient data are available regarding usage during pregnancy. 

Breastfeeding warnings:  

No information is available regarding the usage of the drug during pregnancy. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/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 available 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 

saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. DPP-4 is an enzyme which breaks down incretin hormones, particularly glucagon-like peptide-1 (GLP-1).

By inhibiting DPP-4, saxagliptin increases the levels of active GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), both of which regulate blood sugar levels. 

metformin primarily works by decreasing hepatic glucose production (gluconeogenesis) and improving insulin sensitivity in peripheral tissues, such as muscle and adipose tissue. It also increases glucose uptake and utilization by the muscles. 

Pharmacodynamics 

saxagliptin enhances glucose-dependent insulin secretion from pancreatic beta cells and suppresses glucagon release from pancreatic alpha cells. These effects help to reduce blood glucose levels, particularly after meals. saxagliptin has a glucose-dependent mode of action, meaning its effects are more pronounced when blood glucose levels are elevated. 

Pharmacokinetics 

Absorption 

saxagliptin is well absorbed after oral administration, with an absolute bioavailability of approximately 50%. Food does not significantly affect its absorption. 

metformin is rapidly and almost completely absorbed after oral administration. The absolute bioavailability is approximately 50-60%. 

Distribution 

saxagliptin has a moderate volume of distribution, indicating that it is distributed throughout the body. It is approximately 69% bound to plasma proteins, primarily to albumin. 

metformin has a small volume of distribution, indicating that it remains primarily in the bloodstream and is not extensively distributed into tissues. 

Metabolism 

saxagliptin undergoes extensive hepatic metabolism via cytochrome P450 enzymes, primarily CYP3A4/5 and to a lesser extent, CYP2C8. The major metabolite, 5-hydroxy saxagliptin, is formed through cytochrome P450-mediated oxidation. 

metformin is not significantly metabolized in the body. It is excreted unchanged in the urine. 

Elimination and Excretion 

The primary route of elimination for saxagliptin and its metabolites is through feces, with approximately 24% of the dose excreted in the urine. The elimination half-life of saxagliptin is approximately 2.5 hours. 

The kidneys play a crucial role in the elimination of metformin. The drug is eliminated from the body primarily by renal excretion, with approximately 90% of the administered dose. It gets excreted unchanged in the urine. 

Adminstartion

Administration: 

saxagliptin/metformin can be taken with or without food. However, it is usually recommended to take it with meals to reduce the risk of gastrointestinal side effects associated with metformin. 

Your healthcare provider will determine the dosage of saxagliptin/metformin based on factors such as your current blood sugar levels, response to treatment, and other individual considerations.  

Patient Information Leaflet

Patient information leaflet 

Generic Name: saxagliptin/metformin 

Pronounced: sax-a-glip-tin/met-for-min 

Why do we use saxagliptin/metformin? 

saxagliptin/metformin is a combination medication used to manage type 2 diabetes. It combines two different classes of drugs: saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and metformin, a biguanide.