Insulin Degludec And Liraglutide

Insulin Degludec And Liraglutide Uses, Dosage, Side Effects, Food Interaction and all others data.

The primary activity of insulin, including Insulin Degludec, is regulation of glucose metabolism. Insulin and its analogues lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin also inhibits lipolysis and proteolysis, and enhances protein synthesis. Insulin Degludec forms multihexamers when injected into the subcutaneous tissue resulting in a subcutaneous insulin degludec depot. The protracted time action profile of Insulin Degludec is predominantly due to delayed absorption of insulin degludec from the subcutaneous tissue to the systemic circulation and to a lesser extent due to binding of insulin degludec to circulating albumin.

Insulin is a natural hormone produced by beta cells of the pancreas. In non-diabetic individuals, the pancreas produces a continuous supply of low levels of basal insulin along with spikes of insulin following meals. Increased insulin secretion following meals is responsible for the metabolic changes that occur as the body transitions from a postabsorptive to absorptive state. Insulin promotes cellular uptake of glucose, particularly in muscle and adipose tissues, promotes energy storage via glycogenesis, opposes catabolism of energy stores, increases DNA replication and protein synthesis by stimulating amino acid uptake by the liver, muscle and adipose tissue, and modifies the activity of numerous enzymes involved in glycogen synthesis and glycolysis. Insulin also promotes growth and is required for the actions of growth hormone (e.g. protein synthesis, cell division, DNA synthesis). Insulin detemir is a long-acting insulin analogue with a flat and predictable action profile. It is used to mimic the basal levels of insulin in diabetic individuals. The onset of action of insulin detemir is 1 to 2 hours and its duration of action is up to 24 hours. Interestingly, it has a lower affinity (30%) for the insulin receptor than human insulin.

Liraglutide is an acylated analog of human glucagon-like peptide 1 (GLP-1), an endogenous incretin hormone and acts as a GLP-1 receptor agonist. Activation of GLP-1 receptor stimulates insulin secretion and suppression of glucagon secretion in a glucose-dependent manner. It also delays gastric emptying thus reduces the rate of postprandial glucose present in the circulation. It has lowering effects of fasting, premeal and postprandial glucose; with a decrease in HbA1c by approx 1%.

Liraglutide is a once-daily GLP-1 derivative for the treatment of type 2 diabetes. The prolonged action of liraglutide is achieved by attaching a fatty acid molecule at position 26 of the GLP-1 molecule, enabling it to bind reversibly to albumin within the subcutaneous tissue and bloodstream and be released slowly over time. Binding with albumin results in slower degradation and reduced elimination of liraglutide from the circulation by the kidneys compared to GLP-1. The effect of liraglutide is the increased secretion of insulin and decreased secretion of glucagon in response to glucose as well as slower gastric emptying. Liraglutide also does not adversely affect glucagon secretion in response to low blood sugar.

Insulin Degludec And Liraglutide
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Insulin Degludec And Liraglutide
Generic	Insulin Degludec + Liraglutide
Weight	100units + 3.6mg/ml,
Type	Subcutaneous Solution, Subcutaneous
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Insulin Degludec is used for once-daily treatment of adults with diabetes mellitus to improve glycemic control. Insulin Degludec is not recommended for the treatment of diabetic ketoacidosis.

Liraglutide is used for an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease

Insulin Degludec And Liraglutide is also used to associated treatment for these conditions: Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes MellitusBMI >30 kg/m2, Cardiovascular Risk Reduction, Type 2 Diabetes Mellitus

How Insulin Degludec And Liraglutide works

Insulin detemir binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signalling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism.

Liraglutide is an acylated synthetic glucagon-like peptide-1 analog. Liraglutide is an agonist of the glucagon-like peptide-1 receptor which is coupled to adenylate cyclase. The increase in cyclic AMP stimulates the glucose dependant release of insulin, inhibits the glucose dependant release of glucagon, and slows gastric emptying to increase control of blood sugar.

Dosage

Insulin Degludec And Liraglutide dosage

Insulin Degludec is ultra long-acting basal insulin for once-daily at any time of the day, preferably at the same time every day.

Patients with type 2 diabetes mellitus: The recommended daily starting dose is 10 units followed by individual dosage adjustments.

Patients with type 1 diabetes mellitus: Insulin Degludec is to be used once-daily with meal-time insulin and requires subsequent individual dosage adjustments.

In patients with type 2 diabetes mellitus,Insulin Degludec can be administered alone or in any combination with oral anti-diabetic medicinal products, GLP-1 receptor agonists and bolus insulin. In type 1 diabetes mellitus, Insulin Degludec must be combined with short-/rapid-acting insulin to cover mealtime insulin requirements. On occasions when administration at the same time of the day is not possible, Insulin Degludec allows for flexibility in the timing of insulin administration. A minimum of 8 hours between injections should always be ensured. Patients who forget a dose, are advised to take it upon discovery and then resume their usual once-daily dosing schedule.

Inject Liraglutide subcutaneously once-daily at any time of day, independently of meals. Initiate Liraglutide with a dose of 0.6 mg per day for one week. The 0.6 mg dose is a starting dose intended to reduce gastrointestinalsymptoms during initial titration, and is not effective for glycemic control. After one week at 0.6 mg per day, the dose should be increased to 1.2 mg. If the 1.2 mg dose does not result in acceptable glycemic control, the dose can be increased to 1.8 mg. If a dose is missed, resume the once-daily regimen as prescribed with the next scheduled dose. Do not administer an extra dose or increase in dose to make up for the missed dose.

If more than 3 days have elapsed since the last Liraglutide dose, reinitiate Liraglutide at 0.6 mg to mitigate any gastrointestinal symptoms associated with reinitiation of treatment. Upon reinitiation, Liraglutide should be titrated at the discretion of the prescriber.

Inspect visually prior to each injection. Only use if solution is clear, colorless, and contains no particles.
Inject Liraglutide subcutaneously in the abdomen, thigh or upper arm. No dose adjustment is needed if changing the injection site and/or timing.
When using Liraglutide with insulin, administer as separate injections. Never mix.
It is acceptable to inject Liraglutide and insulin in the same body region but the injections should not be adjacent to each other.

Side Effects

Nasopharyngitis, Severe hypoglycemic episode, Upper respiratory tract infection, Headache, Diarrhea, Sinusitis, Gastroenteritis, Injection site reactions, Peripheral edema

Nausea, diarrhoea, vomiting, constipation, headache, dizziness, upper resp tract infection, influenza, sinusitis, nasopharyngitis, UTI, back pain, dehydration. Increased blood calcitonin, goitre, and thyroid neoplasms.

Toxicity

Observe for signs and symptoms of hypoglycemia, hypokalemia, and fluid retention and heart failure with concomitant use of Thiazolidinediones. Pregnancy Category C

There is no clinical significance of race or ethnicity on the safety or efficacy of liraglutide. Geriatric patients do not experience clinically significant differences in pharmacokinetics though patients at an especially advanced age may be more susceptible to adverse effects. Female patients have reduced clearance of liraglutide but no dose adjustment is necessary. The risk and benefit of liraglutide in pregnancy must be weighed before prescribing. In animal studies, liraglutide is associated with an increased risk of embryonic death and fetal abnormalities though an HbA1c > 7 is also associated with a 20-25% risk of birth defects. In animal studies, liraglutide is present in the milk of lactating rats at half the plasma concentration of the mother but these results may not translate to humans. Because it is not known if liraglutide is present in breast milk and the effects on infants are also unknown, the risk and benefit of liraglutide in breastfeeding must be considered before prescribing. Liraglutide was shown to be safe and effective in patients up to 160kg in weight but has not been studied in patients at a higher weight. A patient's weight significantly affects the pharmacokinetics of liraglutide. Liraglutide has not been investigated for use in pediatric patients. No dosage adjustments are necessary in patients with renal impairment but studies have not been performed in patients with end stage renal disease. There are no recommendations on dosage adjustment in patients with hepatic impairment, though caution should still be exercised when prescribing to this population.

Precaution

Insulin Degludecs must not be injected into a vein (intravenously) or a muscle (intramuscularly) and must not be used in infusion pumps.

There is no experience with Insulin Degludec in children and adolescents under 18 years of age.

Patients with history of pancreatitis or alcoholism, inflammatory bowel disease, diabetic gastroparesis, pre-existing thyroid disease. Renal impairment. Pregnancy and lactation.

Interaction

Decreased hypoglycaemic effect with corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, phenothiazine derivatives, somatropin, sympathomimetic agents, thyroid hormones, oestrogens, progestins (e.g. in oral contraceptives), protease inhibitors and atypical antipsychotic (e.g. olanzapine and clozapine). Increased hypoglycaemic effect with oral antidiabetic agents, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAOIs, pentoxifylline, propoxyphene, salicylates and sulfonamide antibiotics. Decreased insulin resistance with octreotide and lanreotide. Increased risk of wt gain and peripheral oedema with pioglitazone, rosiglitazone. Decreased effect of sermorelin.

Increased risk of hypoglycaemia when used w/ insulin secretagogues (e.g. sulfonylurea, meglitinide). May affect absorption of concomitantly administered oral drugs due to slow gastric emptying.

Volume of Distribution

13L.

Elimination Route

In patients with type 1 diabetes, after 8 days of once daily subcutaneous dosing with 0.4 U/kg, maximum degludec concentrations of 4472 pmol/L were attained at a median of 9 hours (tmax). After the first dose of, median onset of appearance was around one hour. The glucose lowering effect lasted at least 42 hours after the last of 8 once-daily injections. Insulin degludec concentration reach steady state levels after 3-4 days.

Bioavailability of liraglutide after subcutaneous injection is approximately 55% and maximum concentrations are reached after 11.7 hours.

Half Life

The half-life after subcutaneous administration is determined primarily by the rate of absorption from the subcutaneous tissue. On average, the half-life at steady state is approximately 25 hours independent of dose.

Terminal half life of 13 hours.

Clearance

The mean apparent clearance of insulin degludec is 0.03 L/kg (2.1 L/h in 70 kg individual) after single subcutaneous dose of 0.4 units/kg.

1.2L/h.

Elimination Route

6% excreted in urine and 5% excreted in feces.

Pregnancy & Breastfeeding use

Pregnant Women: There is no clinical experience from well-controlled studies with Insulin degludec in pregnant women. Animal reproduction studies have not revealed any differences between insulin degludec and human insulin regarding embryotoxicity and teratogenicity. Animal reproduction studies are not always predictive of human response; therefore, Insulin degludec should not be used during pregnancy unless the potential benefits to the mother justify the potential risks to the fetus

Nursing Women: There is no clinical experience from well controlled studies with Insulin degludec during breast-feeding. It is unknown whether insulin degludec is excreted in human milk. In rats, insulin degludec was secreted in milk; the concentration in milk was lower than in plasma.

Pregnancy category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Hypersensitivity to the active substance or to any of the excipients. Hypoglycaemia, Hyperglycaemia, Eye disorder.

Personal or family history of medullary thyroid carcinoma (MTC). Patients with multiple endocrine neoplasia syndrome type 2; type 1 DM or diabetic ketoacidosis. Liraglutide is not a substitute for insulin.

Special Warning

Geriatrics (≥ 65 years of age): No overall clinical differences in safety or effectiveness have been observed between elderly and adult patients.

Pediatrics (< 18 years of age): Insulin Degludec is not indicated for use in the pediatric population

Acute Overdose

Overdoses have been reported in clinical trials and post-marketing use of Liraglutide. Effects have included severe nausea and severe vomiting. In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms.