metformin/sitagliptin                                              

Action and Spectrum

Actions and Spectrum 

metformin: 

metformin is taken orally to help manage type 2 diabetes by decreasing glucose production in the liver and increasing insulin sensitivity in muscle cells. Additionally, it may be prescribed to treat other conditions like polycystic ovary syndrome (PCOS), gestational diabetes, and prediabetes. 

sitagliptin: 

sitagliptin is an oral medication categorized as a dipeptidyl peptidase-4 (DPP-4) inhibitor, which works by increasing the production of insulin in response to meals and decreasing the amount of glucose made by the liver. It can be prescribed as a standalone treatment or with other antidiabetic medications like metformin, sulfonylureas, or insulin. 

Drug Interaction

Adverse Reaction

Frequency defined  

1-10% 

Vomiting (1.1%) 

Hypoglycemia (2.1%) 

Abdominal pain (2.2%) 

Diarrhea (2.4%)  

Frequency Not Defined 

Lactic acidosis (rare) 

Exfoliative disorder of skin of scalp 

Black Box Warning

Black Box Warning:  

Lactic acidosis 

Contraindication / Caution

Contraindication/Caution: 

Hypersensitivity to either metformin or sitagliptin.  

renal impairment patients. 

The drug is contraindicated in individuals with severe hepatic impairment.   

The drug is contraindicated in patients with diabetic ketoacidosis. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

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 pharmacology of metformin/sitagliptin involves the reduction of hepatic glucose production, improved insulin sensitivity, and increased insulin secretion in a glucose-dependent manner. 

Pharmacodynamics:  

metformin primarily decreases hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis. Conversely, sitagliptin acts by inhibiting DPP-4, an enzyme that degrades incretin hormones such as GLP-1 and glucose-dependent insulinotropic polypeptide (GIP).  

Pharmacokinetics: 

Absorption 

metformin is absorbed through the gastrointestinal tract, primarily in the upper small intestine, and is not extensively metabolized before absorption. sitagliptin is rapidly absorbed after oral administration, The absorption of sitagliptin is not affected by food. 

Distribution 

metformin is minimally bound to plasma proteins, and its volume of distribution is approximately 654 L. It is distributed to erythrocytes, but does not accumulate in red blood cells. The distribution of sitagliptin is similar to that of metformin, with a volume of distribution of approximately 198 L.  

Metabolism 

metformin is not metabolized by the liver or any other organ, but is eliminated unchanged in urine. sitagliptin is primarily metabolized by the liver via cytochrome P450 (CYP) 3A4 and CYP2C8 to form inactive metabolites.  

Excretion and elimination 

metformin is primarily eliminated unchanged in urine, and its renal clearance is greater than the glomerular filtration rate, suggesting that the renal tubules actively secrete the drug. The elimination half-life of metformin is approximately 2-4 hours. sitagliptin is eliminated via both renal and hepatic pathways, with approximately 79% of the drug excreted in urine and 13% in feces. The elimination half-life of sitagliptin is approximately 12.4 hours. 

Adminstartion

Administration:  

The medication should be by oral route according to the instructions provided by the healthcare provider, regardless of food intake 

The recommended dosage may be adapted based on the individual patient’s requirements, with a maximum dose of 50 mg/1000 mg administered twice per day 

Patient Information Leaflet

Patient information leaflet 

Generic Name: metformin/sitagliptin 

Why do we use metformin/sitagliptin?  

metformin/sitagliptin is a combination medication for treating type 2 diabetes mellitus.  

The drug can reduce complications associated with diabetes.