ertugliflozin/sitagliptin

Action and Spectrum

Actions and Spectrum 

For ertugliflozin  

Because ertugliflozin is an SGLT2 inhibitor, it functions by preventing the kidneys’ SGLT2 protein from doing its job. Normally, SGLT2 returns glucose from the kidneys’ filtered fluid to the circulation. ertugliflozin reduces blood glucose levels by inhibiting SGLT2, which stops the reabsorption of glucose and increases its outflow through the urine. 

Specific indications for ertugliflozin include the treatment of type 2 diabetes. It is used to enhance glycemic control in adults with type 2 diabetes mellitus in conjunction with diet and exercise. 

For sitagliptin  

sitagliptin functions by inhibiting the DPP-4 enzyme since it is a DPP-4 inhibitor. Incretin hormones including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are broken down by the enzyme DPP-4. By promoting insulin release and inhibiting glucagon secretion, these hormones help to control blood glucose levels. 

Type 2 diabetes control is another indication for the use of sitagliptin. In individuals with type 2 diabetes mellitus, it is used as an addition to diet and exercise to enhance glycemic control. 

Drug Interaction

Adverse Reaction

Frequency defined  

1-10%  

For ertugliflozin 

Headache (2.9-3.5%) 

Vaginal pruritus (2.4-2.8%) 

Renal adverse effects (1.3-2.5%) 

Thirst (1.4-2.7%) 

Increased urination (2.4-2.7%) 

Back pain (1.7-2.5%) 

Male genital mycotic infections (3.7-4.2%) 

Weight decreased (1.2-2.4%) 

Nasopharyngitis (2-2.5%) 

Volume depletion adverse effects (1.9-4.4%) 

Urinary tract infections (4-4.1%) 

>10%  

For ertugliflozin 

Female genital mycotic infections (9.1-12.2%) 

Frequency not defined  

For sitagliptin 

Upper respiratory tract infection 

Abdominal pain 

Diarrhea 

Headache 

Nausea 

Nasopharyngitis 

Post marketing reports  

For sitagliptin 

Hepatic enzyme elevations 

Bullous pemphigoid 

Back pain 

Rhabdomyolysis 

Constipation 

Worsening renal function and acute renal failure 

Acute pancreatitis 

Headache 

Pruritus 

Pain in extremity 

Myalgia 

Tubulointerstitial nephritis 

Vomiting 

Hypersensitivity including anaphylaxis, angioedema, cutaneous vasculitis, rash, urticaria and exfoliative skin conditions 

Black Box Warning

Black Box Warning 

ertugliflozin/sitagliptin does not have any black box warning. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity to ertugliflozin or any of its ingredients that is well known. 
• Hypersensitivity to sitagliptin or any of its ingredients is well-known. 

Caution: 

• Ketoacidosis, vaginal mycotic infections, urinary tract infections, volume depletion, hypotension, renal impairment and hypersensitivity reactions are all possible side effects of ertugliflozin. 
• When treating patients who have had pancreatitis in the past, sitagliptin should be taken cautiously.  
• When used with sulfonylureas or insulin, it may also raise the risk of hypoglycemia. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excretion 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 lack of studies on pregnant women and no evidence of risk to the foetus 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 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  

For ertugliflozin  

A specific inhibitor of sodium-glucose cotransporter 2 (SGLT2) is ertugliflozin. The proximal renal tubules SGLT2 is inhibited, which decreases glucose reabsorption and boosts glucose excretion in the urine. Plasma glucose levels drop as a result of this mechanism, and glycemic control improves. 

For sitagliptin  

Dipeptidyl peptidase-4 (DPP-4) is inhibited by the drug sitagliptin. DPP-4 is an enzyme that breaks down incretin hormones like glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). As a result of sitagliptin’s inhibition of DPP-4, active GLP-1 and GIP levels rise, enhancing glucose-dependent insulin secretion while lowering glucagon secretion and enhancing glycemic control. 

Pharmacodynamics 

For ertugliflozin  

ertugliflozin increases urine glucose excretion and decreases renal glucose reabsorption by inhibiting SGLT2. This method lowers plasma glucose levels, which helps type 2 diabetes mellitus patients have better glycemic control. 

For sitagliptin  

sitagliptin increases the levels of GLP-1 and GIP that are active by inhibiting DPP-4, which improves glucose-dependent insulin production. DPP-4 is an enzyme that breaks down incretin hormones like glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). 

Pharmacokinetics 

Absorption   

ertugliflozin is quickly absorbed when taken orally. About 100% of the bioavailability is absolute. 

Following oral treatment, sitagliptin is effectively absorbed, with an estimated bioavailability of about 87%. 

Distribution 

ertugliflozin has a modest plasma protein binding, ranging from 23.5% to 29.2%. 

Plasma protein binding for sitagliptin is high, at around 38%. 

Metabolism 

Uridine diphosphate-glucuronosyltransferase (UGT) enzymes, particularly UGT1A9, metabolize ertugliflozin predominantly. Inactive metabolites are produced. 

There is very little hepatic metabolism of sitagliptin. It is mainly eliminated in the urine undamaged. 

Elimination and excretion 

ertugliflozin is primarily excreted through the feces, with a minor amount also passing through the urine. 

The majority of sitagliptin is eliminated unaltered in the urine, with some also passing through the feces. 

Adminstartion

Administration 

sitagliptin/ertugliflozin are typically taken orally as tablets. The tablets can be taken with or without food and should be consumed whole with a glass of water. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: ertugliflozin/sitagliptin 

Why do we use ertugliflozin/sitagliptin? 

Adults with type 2 diabetes mellitus are typically treated with the ertugliflozin/ sitagliptin drug. 

It is suggested to help with glycemic management as a supplement to diet and exercise.