empagliflozin and linagliptin

Action and Spectrum

Actions and Spectrum: 

The sodium-glucose co-transporter 2 (SGLT2) protein is inhibited by empagliflozin principally in the renal tubules. This causes the kidneys to absorb less glucose, which causes an increase in urine excretion of glucose and a drop in blood glucose levels. 

The DPP-4 enzyme is the main target of linagliptin’s activity, which it inhibits. Lower blood glucose levels are the result of elevated levels of the incretin hormones GLP-1 and GIP, which stimulate insulin production and inhibit glucagon release. 

The variety of ailments that empagliflozin and linagliptin is used to treat is referred to as its spectrum. empagliflozin may also be used to treat individuals with heart failure who have a decreased ejection fraction (HFrEF), even though it is often used to treat type 2 diabetes

Drug Interaction

Adverse Reaction

Frequency Defined  

1-10% 

Increased hematocrit (2.8%) 

Nasopharyngitis (5.9-6.6%) 

Upper respiratory tract infection (7%) 

Hypoglycemia (2.2-3.6%) 

Increased LDL-C (4.6-6.5%) 

Post marketing Reports 

Ketoacidosis 

Hypersensitivity reactions including angioedema, anaphylaxis, and exfoliative skin conditions 

Urosepsis and pyelonephritis 

Necrotizing fasciitis of the perineum  

Acute pancreatitis, including fatal pancreatitis 

Acute kidney injury 

Constipation 

Severe and disabling arthralgia 

Bullous pemphigoid 

Skin reactions (e.g., rash, urticaria) 

Rhabdomyolysis 

Mouth ulceration, stomatitis 

>10% 

Urinary tract infection (11.4 to 12.5%) 

Black Box Warning

Black Box Warning 

The danger of lower limb amputations is highlighted in the black box warning for empagliflozin. According to studies, people on empagliflozin had a higher incidence of lower limb amputations than those taking a placebo. 

The caution states that individuals who have serious lower limb problems such ulceration, osteomyelitis, or gangrene should stop using empagliflozin. The danger of acute pancreatitis, a severe and potentially fatal illness, is highlighted in the black box warning for linagliptin.

In accordance with the caution, linagliptin should be stopped in patients who experience pancreatitis-related signs or symptoms, such as persistent, excruciating stomach pain that occasionally radiates to the back and may be followed by vomiting. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

For empagliflozin 

• Intolerance to empagliflozin or any of its ingredients. 
• Dialysis is necessary if there is severe renal impairment (eGFR 30 mL/min/1.73 m2), end-stage renal disease, or both. 

For linagliptin 

• hypersensitivity to any of linagliptin’s ingredients 

Caution 

For empagliflozin 

• mild renal impairment patients. 
• Individuals who have had urothelial carcinoma in the past or who have a family history of the disease. 
• People who have experienced genital mycotic infections in the past or who are at higher risk for developing them. 
• patients who are hypotensive or have lost volume. 

For linagliptin  

• those who have already had pancreatitis. 
• patients with end-stage renal illness or severe renal impairment. 
• sufferers of heart failure. 
• those who have previously experienced hypersensitivity responses to other DPP-4 inhibitors. 

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 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 empagliflozin  

A sodium-glucose co-transporter 2 (SGLT2) inhibitor is empagliflozin. It functions by preventing the kidneys from reabsorbing glucose, which raises the amount of glucose excreted in urine and lowers blood glucose levels. 

For linagliptin  

Dipeptidyl peptidase-4 (DPP-4) is inhibited by linagliptin. It functions by preventing the DPP-4 enzyme from degrading the incretin hormones GLP-1 and GIP. This results in higher amounts of these hormones, which in turn promote the release of insulin and inhibit the release of glucagon, lowering blood sugar levels. 

Pharmacodynamics 

For empagliflozin  

empagliflozin has a hypoglycemic impact by decreasing renal glucose reabsorption, which causes an increase in urine glucose excretion. As a result, the level of blood sugar is generally decreased. 

empagliflozin helps people lose weight by causing their urine to lose calories and by lowering their insulin levels, which can decrease their appetite and calorie consumption. 

empagliflozin has been demonstrated to lower blood pressure in people with type 2 diabetes. This effect may be related to the drug’s diuretic properties and decreased vascular volume. 

For linagliptin 

linagliptin’s ability to block DPP-4 results in an increase in the incretin hormones GLP-1 and GIP, which lowers blood sugar levels. 

In individuals with type 2 diabetes and high cardiovascular risk, linagliptin has been found to have positive effects on the heart, including a decreased risk of cardiovascular mortality, nonfatal myocardial infarction, and stroke 

Pharmacokinetics 

Absorption   

For empagliflozin 

With oral treatment, empagliflozin is quickly absorbed; peak plasma concentrations are attained in 1.5 hours. 

For linagliptin 

After oral treatment, linagliptin is quickly absorbed, reaching peak plasma concentrations in 1 to 2 hours. 

Distribution 

For empagliflozin 

The large volume of distribution of empagliflozin suggests that it is widely dispersed throughout the body. Around 86% of it is linked to plasma proteins. 

For linagliptin 

A modest volume of distribution for linagliptin suggests that it is mostly confined to the blood circulation. Around 70% of it is bonded to plasma proteins 

Metabolism   

For empagliflozin 

The liver’s glucuronidation process is the main way that empagliflozin is broken down, with cytochrome P450 (CYP) enzymes playing a minor role. empagliflozin 25-O-glucuronide is the main metabolite that is present in the blood. 

For linagliptin 

linagliptin is largely hydrolysed in the liver to an inactive metabolite, with minimal involvement from CYP enzymes. 

Elimination and excretion 

For empagliflozin  

Around 84% of the dosage of empagliflozin and its derivatives is recovered in the urine, with the remaining 9% ending up in the feces. Around 12.4 hours pass until the substance is eliminated. 

For linagliptin 

Around 90% of the dosage of linagliptin and its derivatives is recovered in the feces, with the remaining 5% found in the urine. The half-life of elimination is 12 to 14 hours. 

Adminstartion

Administration:  

For empagliflozin 

With or without breakfast, empagliflozin is typically taken once every day in the morning. 

If necessary and acceptable, the beginning dose of 10 mg per day may be raised to 25 mg per day. 

For maximum effectiveness, empagliflozin must be taken on a regular basis. 

empagliflozin shouldn’t be chewed, split, or crushed; it should be eaten entire a glass of water. 

For linagliptin 

It is typical to take linagliptin once day, with or without meals. 

Regardless of food consumption or renal function, the daily dosage is 5 mg. 

For linagliptin to be most effective, it must be taken often. 

linagliptin should not be chewed, divided, or crushed; it should be consumed entire with a glass of water. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: empagliflozin and linagliptin 

Why do we use empagliflozin and linagliptin? 

For empagliflozin 

In individuals with type 2 diabetes mellitus, it is used as an addition to diet and exercise to enhance glycemic control. 

In individuals with type 2 diabetes mellitus, existing cardiovascular disease, or numerous cardiovascular risk factors, empagliflozin has also been found to offer cardiovascular and renal advantages.  

For linagliptin 

linagliptin is an anti-diabetic drug that can be taken alone or in conjunction with other drugs such metformin, sulfonylureas, or insulin.