Insulin degludec + Insulin aspart

Insulin degludec+ Insulin aspart is an anti-diabetic Agent belonging to the pharmacological class of long-acting Insulin and fast-acting insulins.

Combining Insulin degludec and Insulin aspart is approved for treating type 1 and type 2 diabetes mellitus in adults. This works by helping to control blood sugar levels and manage diabetes more effectively.

Insulin degludec and insulin aspart are administered subcutaneously. After injection, they are absorbed into the bloodstream, distributed to various body tissues, and metabolized. Degludec is primarily metabolized into inactive compounds, while aspart is rapidly metabolized into active Insulin. Both are eliminated from the body via urine and metabolism.

The common side effect of Insulin degludec+ Insulin aspart is low blood sugar levels (hypoglycemia).

Insulin degludec+ Insulin aspart is an injectable solution (prefilled pen).

Insulin degludec+ Insulin aspart is available in the United States, Canada, the United Kingdom, Germany, France and Australia.

Insulin degludec+ Insulin aspart is an Antidiabetic Agent belonging to the pharmacological class of long-acting Insulin and fast-acting insulins.

Insulin degludec: Regulation of glucose metabolism is the primary function of Insulin, including Insulin Degludec. Insulin and its analogues reduce blood sugar by blocking hepatic glucose synthesis and boosting peripheral glucose absorption, particularly by skeletal muscle and fat. In addition, Insulin blocks lipolysis and proteolysis while promoting protein synthesis. A subcutaneous insulin degludec depot is produced when insulin degludec is injected into the subcutaneous tissue and generates multi-hexamers. Insulin Degludec has a prolonged period of action, mainly caused by delayed absorption into the bloodstream from subcutaneous tissue and, to a lesser extent, by binding to circulating albumin.

Insulin aspart: The insulin receptor (IR), a heterotetrameric protein composed of two transmembrane beta units and two extracellular alpha units, binds to insulin aspart. The tyrosine kinase activity in the beta subunit of the receptor is stimulated when Insulin binds to the alpha subunit of its receptor. Insulin receptor substrates (IRS) proteins, Cbl, APS, Shc, and Gab 1, are just a few examples of the many intracellular substrates that the bound receptor phosphorylates and autophosphorylates. These proteins activate downstream signalling molecules, including PI3 kinase and Akt. Protein kinase C (PKC) and Glucose transporter 4 (GLUT4), both of which are essential for metabolism and catabolism, are controlled by Akt. In humans, Insulin is stored as hexamers, but only insulin monomers can interact with IR. Aspartic acid is substituted for the proline residue at position B28, which decreases the propensity to form hexamers, increases the rate of absorption, has a quicker beginning of action, and has a shorter duration of action.

Synergistic Benefits: Insulin degludec and insulin aspart have synergistic effects that help treat diabetes. While insulin aspart provides a fast-acting bolus insulin action to control blood sugar increases after meals, insulin degludec provides long-acting basal insulin support for stable blood glucose management throughout the day. This combination improves glycemic control and lowers the risk of hypoglycemia in people with diabetes by allowing for flexible dosing to manage postprandial and fasting hyperglycemia.

Insulin degludec+ Insulin aspart is available in injectable solutions.

Prefilled pen: To use the insulin degludec+ Insulin aspart prefilled pen, identify the injection site, disinfect it, attach a new needle, prepare the pen, dial the dose, inject, and cautiously dispose of the needle. For proper use, adhere to the doctor's recommendations.

The physician determines the exact dosage and timing based on the patient's needs and blood sugar levels.

Insulin degludec+ Insulin aspart can be used in the following health conditions:

Insulin degludec: Insulin degludec helps maintain stable blood sugar levels and lowers the risk of high or low blood sugar episodes. It replaces the Insulin that is typically produced in the body. It helps regulate blood sugar levels and synthesizes energy from sugar by promoting glucose entry into cells.

Insulin aspart: Insulin aspart aids in controlling high blood glucose (sugar) levels, allowing for better post-meal blood sugar control. It provides flexibility in dosing, reducing the risk of hypoglycemia. Compatible with insulin pumps, it improves meal planning and quality of life. When used effectively, it helps achieve target A1C levels, lowering the risk of complications.

Insulin degludec+ Insulin aspart together provide several essential benefits for treating diabetes. Long-acting basal insulin protection is provided by insulin degludec, resulting in stable blood sugar levels for a more extended period. In the meanwhile, to prevent post-meal glucose rises, insulin aspart provides fast-acting bolus insulin activity—better glycemic control results from this combination's cautious control over postprandial hyperglycemia and fasting.

Indicated to aid patients with diabetes mellitus improve their glycemic control.

Not recommended for treating diabetic ketoacidosis.

Parenterally: Insulin degludec+ Insulin aspart is an injectable solution (prefilled pen) that can be taken parenterally, preferably subcutaneously once or twice daily with any main meal, and for pediatric patients, once daily with any main meal. It's essential to consider rapid- or short-acting Insulin at other meals if necessary. For those with type 1 diabetes, optimal glucose control may require using rapid- or short-acting Insulin at meals when not using Insulin degludec/insulin aspart 70/30. The dose should be personalized and titrated according to metabolic needs, blood glucose results, and glycemic targets. Adjusting the amount based on fasting blood glucose measurements is crucial. The injection site should be subcutaneous in the thigh, upper arm, or abdomen. Dose adjustments are recommended every 3-4 days. Changes in physical activity, meal patterns, renal or hepatic function, or acute illness may necessitate dose adjustments to minimize the risk of hypoglycemia or hyperglycemia. If a dose is missed, it should be taken with the following main meal and then continue the regular dosing schedule; taking an extra amount to compensate for the missed one is not recommended.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Insulin degludec+ Insulin aspart is an injectable solution (prefilled pen).

Insulin degludec + Insulin aspart should be used in treating type 2 diabetes mellitus, along with appropriate dietary restrictions.

While taking Insulin degludec + Insulin aspart, maintain an appropriate diet, primarily focusing on regulating carbohydrate intake and consuming a balanced and healthy meal plan.

Patients should maintain a consistent carbohydrate (foods with a low glycemic index) intake from meal to meal and day to day. This consistency helps in dosing Insulin appropriately and managing blood glucose levels effectively.

Patients should avoid excessive alcohol consumption to reduce the risk of hypoglycemia and dehydration.

While taking this combination, it is advised to stay hydrated, consume a rich-balanced diet low in saturated fats and cholesterol—and drink plenty of vegetables, whole grains, fruits, and lean proteins in meals.

The dietary restriction should be individualized as per patient requirements.

Insulin degludec+ Insulin aspart may be contraindicated in the following conditions:-

Consume foods with a low glycemic index for more stable blood glucose levels.

The adverse reactions related to Insulin degludec+ Insulin aspart can be categorized as:-

Common Adverse Effects: Nasopharyngitis, Severe hypoglycemia

Less Common Adverse Effects: Upper Respiratory Tract infection, influenza, headache, peripheral oedema, injection site reaction

Rare Adverse Effects: Allergic reaction, lipodystrophy

Localized injection-site cutaneous amyloidosis

Hypokalemia

Excessive sensitivity

The clinically relevant drug interactions of Insulin degludec+ Insulin aspart are briefly summarized here:

The most common side effects of Insulin degludec+ Insulin aspart include:

Headache

Skin rash

Low blood sugar is commonly referred to as hypoglycemia.

Insulin degludec+ Insulin aspart should be prudent in the following particular population groups.

Pregnancy Category C: Use with caution if the benefits outweigh the risks.

There is a lack of information in the published literature and available data from one unpublished trial regarding the use of insulin degludec during pregnancy that would suggest a drug-associated risk of significant congenital disabilities, miscarriage, or other unfavourable outcomes for either the mother or the fetus.

Those with pre-gestational diabetes are more likely to experience hypo- or hyperglycemia during pregnancy; uncontrolled diabetes during pregnancy raises the risk of diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm birth, stillbirth, and delivery complications for the mother; unchecked diabetes during pregnancy increases the risk of significant congenital disabilities, stillbirth, and morbidity related to macrosomia.

The effects of a drug on a breastfed infant, the production of milk, and the presence of insulin degludec in rat milk are all unknown. A single, small published study found that exogenous Insulin, including insulin aspart, was present in human milk; however, the effects on the breastfed infant and milk production still need to be better understood. The benefits of breastfeeding for the mother's health and development should be taken into account, as well as the mother's clinical need for Insulin, any potential adverse effects on her breastfed child therapy, or any underlying maternal condition.

Pediatric patients have shown that insulin degludec and aspart are safe and effective. Their safety profile is comparable to that of adults, and they effectively enhance glycemic control. Individualized care and careful observation are crucial.

<1 year: Not studied

≥1 year:

Type 1 diabetes mellitus: Approximately one-third to half of the daily insulin dose; generally speaking, the remaining daily insulin dose should be given as a short- or rapid-acting insulin, split between each daily meal; in patients with type 1 diabetes who are insulin-naïve, the initial total daily insulin dose can be determined using 0.2–0.4 units/kg.

<1 year: Not studied

≥1 year:

To reduce the risk of hypoglycemia, administer insulin degludec/insulin aspart 70/30 80% of the total daily mixed insulin dose once daily with the main meal.

Patients who also take short- or rapid-acting insulin at mealtimes should continue taking it at the same dose during meals that are not covered by insulin degludec/insulin aspart 70/30.

< 1 year: Not studied

≥1 year:

Aspart 70/30 and insulin degludec should be started at 80% of the extended- or intermediate-acting insulin component of the daily regimen to reduce the risk of hypoglycemia. The medication should be taken once daily with the primary meal of the day.

Patients on short- or rapid-acting Insulin should continue taking it at the same dose during meals not covered by insulin degludec + insulin aspart 70/30.

In research comparing healthy people with those with hepatic impairment (mild, moderate, and severe), no differences in the pharmacokinetics of insulin degludec + Insulin aspart were observed. Dosage adjustment may be individualized based on the patient's hepatic impairment.

In research comparing healthy people with those with hepatic impairment (mild, moderate, and severe), no differences in the pharmacokinetics of insulin degludec + Insulin aspart were observed. Dosage adjustment may be individualized based on the patient's hepatic impairment.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Insulin degludec + Insulin aspart. Overconsumption of Insulin degludec+ Insulin aspart could lead to hypoglycemia with symptoms like shakiness, sweating, confusion, and headache.

There is no specific antidote or treatment for excessive intake of Insulin degludec + Insulin aspart. However, immediate medical attention is essential. Insulin degludec + Insulin aspart should be terminated immediately when an overdose is In cases of overdose, close medical attention is crucial. Insulin degludec + Insulin aspart should be discontinued if an overdose is suspected or if unusual symptoms occur after ingestion.

If mild or moderate, give oral glucose, candies, or other high-sugar foods. For severe cases, administer intravenous dextrose and glucagon.

Continuous monitoring of blood glucose is crucial to ensure it stabilizes within a safe range. Other supportive measures may be employed to address associated symptoms and complications.

Insulin degludec: The beta cells in the pancreas produce the hormone insulin regularly. The pancreas continuously generates low amounts of basal Insulin in non-diabetics and increases insulin levels after meals. The metabolic alterations that occur as the body shifts from a postabsorptive to an absorptive state are brought on by increased insulin secretion after meals. Insulin encourages cellular uptake of glucose, especially in muscle and fatty tissues, enhances energy storage via glycogenesis, increases DNA replication, and fights against the catabolism of energy stores and protein synthesis by increasing the amino acid uptake by the liver, muscle and adipose tissue, and changes the activity of many enzymes involved in glycogen synthesis and glycolysis. The effects of growth hormone, including protein synthesis, cell division, and DNA synthesis, require Insulin, which also stimulates growth. With an unaltered and predictable action profile, insulin detemir is a long-acting insulin analogue. The basal insulin levels in people with diabetes are mimicked by it. Insulin detemir takes up to 24 hours to start working and 1 to 2 hours to finish. Weirdly, compared to human Insulin, it has a lesser affinity for the insulin receptor (30%).

Insulin aspart: The beta cells in the pancreas produce the hormone insulin naturally. A basal insulin level is augmented in non-diabetic people by rises in insulin levels after meals. The metabolic alterations as the body shifts from a postabsorptive to an absorptive state are caused when postprandial insulin increases. Insulin stimulates amino acid uptake by the liver, muscle, and adipose tissue, which increases cellular uptake of glucose, especially in muscle and fatty tissues. Insulin also promotes energy storage through glycogenesis, fights against the catabolism of energy stores, increases DNA replication and protein synthesis, and modifies the activity of many enzymes involved in glycogen synthesis and glycolysis. The effects of growth hormone, including protein synthesis, cell division, and DNA synthesis, require insulin, which also stimulates growth.

Insulin degludec: Maximum insulin degludec concentrations of 4472 pmol/L were achieved in individuals with type 1 diabetes following eight days of once-daily subcutaneous treatment with 0.4 U/kg (tmax). The median appearance after the first dose began around an hour later. The final of eight once-daily injections had a glucose-lowering impact for at least 42 hours. It takes 3–4 days for the concentration of insulin degludec to stabilize.

Insulin aspart: The median time to maximal insulin aspart concentration in these experiments was 40 to 50 minutes against 80 to 120 minutes for ordinary human Insulin, respectively, in tests of healthy volunteers and patients with type 1 diabetes. When administered subcutaneously, Insulin Aspart absorbs more quickly than human Insulin, acts more quickly, and lasts less time than conventional human Insulin. Maximum concentration is attained after 40 to 50 minutes. In individuals with type 1 diabetes, the mean maximal concentration (Cmax) was 82 mU/L when a 0.15 U/kg body weight was administered. No effect is made on the amount or rate of absorption by the injection site.

Insulin degludec: A plasma protein binding of more than 99% in human plasma is consistent with the affinity of insulin degludec to serum albumin. According to the findings of the in vitro protein binding studies, there is no clinically significant interaction between insulin degludec and other protein-bound medications.

Insulin aspart: Unlike conventional human Insulin, insulin aspart has a relatively small (10%) affinity for plasma proteins.

Insulin degludec: The metabolites of insulin degludec are all inert. The liver and kidney mostly carry out insulin metabolism. However, although exogenous Insulin is metabolized mainly through the kidney since it is not immediately transported into the portal system, endogenous Insulin is primarily metabolized by the liver.

Insulin aspart: Insulin aspart is rapidly metabolized in the liver and peripheral tissues. It undergoes enzymatic degradation, mainly by insulin-degrading enzymes and insulin receptor tyrosine kinase.

Insulin degludec: Following subcutaneous administration, the rate at which insulin degludec is absorbed from subcutaneous tissue significantly impacts its half-life. No matter the dosage, the half-life is typically constant in a steady state at around 25 hours. The kidneys eliminate between 30 and 80 per cent of the Insulin in circulation. Following a single 0.4 unit/kg subcutaneous injection, the apparent elimination of insulin degludec averages 0.03 L/kg (corresponding to 2.1 L/h in people weighing 70 kg).

Insulin aspart: The kidneys play a significant part in the elimination of insulin aspart. It acts fast after injection and is swiftly removed from the bloodstream. The half-life of elimination is merely short.