What is the difference between insulin degludec, insulin detemir and insulin glargine?👌👌👌

Among the hypoglycemic drugs, insulin is the most effective one. When the pancreatic function of diabetic patients is severely deteriorated, oral hypoglycemic drugs are contraindicated or the treatment effect is not good, insulin will become a very important therapeutic drug. Among the long-acting insulins, insulin degludec, insulin detemir and insulin glargine are the most commonly used clinically. What is the difference between them?

What types of insulin are commonly used?

Commonly used insulin can generally be divided into recombinant human insulin and human insulin analogs.

• Recombinant human insulin: Protamine recombinant human insulin. It is an intermediate-acting insulin.
• Human insulin analogs: Short-acting human insulin analogs include insulin aspart, insulin lispro, and insulin glulisine. Long-acting human insulin analogs are insulin degludec, insulin detemir and insulin glargine. 

Recombinant human insulin, insulin degludec and insulin detemir formulations are generally valid for 30 months. Insulin glargine preparations are generally valid for 36 months. This is because the A chain of human insulin contains 21 amino acid residues and the B chain contains 30 amino acid residues. Insulin glargine replaces the acid-sensitive asparagine with glycine at position 21 of the A chain. Glycine has a neutral charge. It will be more stable in an acidic environment. Insulin should be sealed and refrigerated at 2 to 8°C before first use. It is sufficient to store insulin at room temperature and it can be stored for up to 8 weeks after first use.

What is the difference in the duration of their action?

In the body, the half-life of insulin is only about a few minutes. The subcutaneous absorption rate is the main factor affecting the duration of insulin action.

	A chain	B chain
Human insulin	Aspartic acid. (21st)	Lysine. (29th) Threonine. (30th)
Insulin degludec	Aspartic acid. (21st)	Lysine. (29th) Glutamate. (30th) 16 carbon fatty diacids.
Insulin detemir	Aspartic acid. (21st)	Lysine. (29th) 14 carbon fatty diacids. (30th)
Insulin glargine	Glycine. (21st)	Lysine. (29th) Threonine. (30th) Arginine. Arginine.

Insulin degludec: The threonine at the end of its B chain has been removed. Instead, a glutamate is attached to the lysine at 29th and a 16-carbon fatty diacid is linked to glutamate. When insulin degludec is injected subcutaneously, it forms stable polyhexamers and continuously releases insulin monomers over an extended period of time. Insulin degludec reversibly binds to albumin after entering the blood. Its protein binding rate is greater than 99%. This can further extend the time to reach the target tissue. The duration of action of insulin degludec is greater than 42 hours.

Insulin detemir: The threonine at the end of its B chain has been removed and a 14-carbon fatty diacid is attached to the lysine at 29th. Insulin detemir formed double hexamers after subcutaneous injection and sustained the release of insulin monomers over an extended period of time. Its duration of action is approximately 16 to 24 hours.

Insulin glargine: It is the addition of two arginines to the end of the B chain of insulin. It changes the isoelectric point of insulin from pH 5.4 to pH 6.7. They form fine precipitates when injected subcutaneously (pH about 7.4). These microprecipitates can sustain the release of insulin monomers for about 30 hours.

What is the difference in the frequency of their use?

The absorption of insulin degludec, insulin detemir, and insulin glargine is smooth and slow. Therefore, they can only be used as basal insulin drugs to lower fasting blood sugar.

	Insulin degludec	Insulin detemir	Insulin glargine
Recommended usage	Administer 1 time a day. It can be administered at any time throughout the day. However, it is best to maintain the same dosing time each day.	Administer 1 to 2 times a day. If administered twice daily, the second dose can be optionally given at dinner, before bedtime or 12 hours after the morning injection.	Administer 1 time a day. It can be administered at any time throughout the day. However, it must maintain the same dosing time each day.
Protein binding rate	>99%	>90%	Unknown
Duration of action	>42 hours	16 to 24 hours	30 hours

What is the difference in their indications?

Their indications will vary slightly.

	Type 1 diabetes	Type 2 diabetes	Gestational diabetes	Diabetes in children
Neutral protamine zinc insulin	✓	✓	✓	✓
Insulin degludec	✓	✓	-	≥6 years old
Insulin detemir	✓	✓	It can be considered for use.	≥6 years old
Insulin glargine	-	✓	-	-

What is the difference between their adverse reactions?

All insulin drugs can cause fatal hypoglycemia. However, insulin degludec has a longer duration of action (>42 hours) and tends to have no peaks, so it has a lower risk of overall hypoglycemia and nocturnal hypoglycemia.

Because insulin increases fat and protein synthesis, it can cause weight gain. However, some studies have pointed out that although insulin detemir has a similar hypoglycemic effect as insulin glargine, it is less likely to cause weight gain.