Medicines

Treatment of diabetes mellitus -antidiabetic drugs

Treatment of diabetes Posted On
Posted By SUMIT SHARMA

Hello everyone! Today we are going to discuss the drugs which are used in the treatment of diabetes. Let’s start the topic – 

If you look in the past, it was challenging to find diabetes. But now, it is very common to have diabetes. 

Diabetes is very devastating in the current situation. It is not only affecting the elderly person, but it may hamper the younger as well.

If we talk about its epidemiology – currently, around 463 million people are living with diabetes. It is predicting that 578 million people will be influential by diabetes in 2030. The number may increase by 700 million in 2045 as per diabetes research and clinical practice, 2019.

Today, you will get information about what drugs are available for the treatment of diabetes. But firstly, we understand what diabetes and its types is – 

 

What exactly is Diabetes?

As per WHO (world health organization) Diabetes is a chronic metabolic disease characterized by elevated blood glucose levels that leading to severe damage to the heart, blood vessels, eyes, kidneys, and nerves.

In other words, if you take food, your body releases insulin. Insulin has a significant role in managing your blood glucose level. 

The homeostasis of insulin is equally essential. Excess insulin production causes hypoglycemia, whereas less insulin production results in spikes in high blood glucose levels. 

The high blood glucose level may lead to diabetes mellitus. 

Sometimes, your body’s cell does not respond to the insulin. In this circumstance, the cells do not use glucose from your blood for energy. 

However, your pancreas continuously releases more insulin. This excess production of insulin desensitizes the insulin receptor. Due to this, your blood glucose level is high even in the presence of an increased insulin level. This is called insulin resistance.

This high blood glucose level may travel to many vital organs. It may cause other complications like ischemic heart disease, atherosclerosis, eye damage, kidney damage, nerve damage, and infection. 

 

 

How many types of diabetes?

Generally, there are two most common types of diabetes, which are Type 1 and Type 2.

In Types 1 Diabetes, you need to depend on insulin injections because your insulin hormone does not produce or synthesize in the pancreas. 

It occurs most commonly in children or young adults, called Juvenile onset diabetes mellitus or IDDM (insulin-dependent diabetes mellitus).

You may have type 1 diabetes if you have an autoimmune disease. Moreover, it may be due to genetic and environmental factors. These things may destroy the beta cells of the pancreas. As a result, it retards the production of insulin.

 

In contrast to Type 2 Diabetes Insulin is desensitized or not secrets from your pancreas.

It means there are two things – insulin resistance and stop insulin secretion. These two mechanisms are responsible for causing high blood glucose levels, which may develop type 2 conditions.

It is also known as Non-Insulin Dependent Diabetes (NIDDM) or maturity-onset diabetes mellitus.

The cause of types 2 diabetes may be –

– abnormality in gluco-receptor of Beta cells (GLUT 2)

– reduction in the number of insulin receptors

– excess of glucagon

– obesity

– genetic defects like – MODY (Maturity Onset Diabetes of Young)

 

 

What are the options available for the treatment of diabetes? 

Here, your priority should control high blood glucose levels. You should try to reduce increased blood glucose levels by lifestyle changes such as a healthy diet and exercise. 

First of all, you need to give more attention to your diet in both types of diabetes, either type-1 or type-2. You will have to reduce the high cholesterol and refined carbohydrates foods. Furthermore, you may follow the low glycemic index foods.

Along with your healthy diet, you need to regularly do moderate physical activity, but exercise should not be highly intense.

If your blood glucose is not managed by diet control and exercise. Then you will have to move towards medicine. But you have to take the medication under the supervision of a physician or specialist like an endocrinologist. They will decide your diabetes treatment plan.  

Some drugs help in the treatment of diabetes –

1.Injections 

These are available in –

a. Insulin

 b. Incretins based drugs – GLP-1 analogs Exenatide (Byetta) and Liraglutide (Victoza)

treatment of diabetes

c. Amylin analogs – Pramlintide (Symlin)

 

 

2.Oral hypoglycaemic agents

These are classified into insulin secretagogues and insulin sensitizers.

 

 

What are the different names of insulin available in the market? 

Insulin analogs are prepared by E-coli bacteria (Escherichia coli). This process is called recombinant DNA technology.

Insulins are classified by their characteristics – 

  • the onset of action(how much time takes for action), 
  • duration of action(how long it will be effective), and
  • peak time(at what time it gives maximum effect).

 

1. Rapid-acting insulin

Rapid-acting insulin quickly drops your blood glucose level for a short time. It starts to work within 5 to 15 mins. So, immediately you need to have your meal after injection.

It remains in your blood for 4-6 hrs, and this type of insulin gives maximum effect around 1-2 hrs. 

Rapid-acting insulin examples are – Glulisine (Apidra), Insulin Lispro (Humalog), Insulin Aspart (Novolog)

Treatment of diabetes

 

Treatment of diabetesTreatment of diabetes

 

 

 

2. Regular/short-acting insulin

This type of insulin enters your bloodstream within 30 mins. So, you need to take your meal after 30 mins. of injection. 

It reaches the maximum concentration in 2-3 hrs, and it is effective for around 3-6 hours. 

Examples of short-acting insulin Human Regular (Humulin R, Novolin R)

 

3. Intermediate-acting insulin

 It gives a slow effect and takes a shot 1 hr before your meal because this type of insulin reaches your bloodstream within 1-2 hrs. So, it is usually prescribed twice a day.

It provides maximum effect in 4-12 hrs, and it is generally effective for 14-24 hrs. 

Examples of intermediate-acting insulin are NPH (Humulin N, Novolin N)

 

4. Long-acting insulin

This type of insulin is not a concern with your meal because it takes 4-6 hours to reach your bloodstream. 

It is often prescribed at bedtime to reduce the fasting blood glucose level efficiently. 

It is effective for more than 24 hours.

 There are some names of long-acting insulin – Insulin glargine (Lantus basaglar), and Insulin Detemir (Levemir)

 

5. Ultra long-acting insulin

This type of insulin gives effectiveness more than 42 hrs. It is also reached in your blood within 4-6 hrs. So, it is not a concern with your meal.

Ultra long-acting insulin examples – Insulin degludec (Tresiba), Insulin glargine (Toujeo)

treatment of diabetes

The most frequent and severe adverse reaction of insulin is hypoglycemia. It stimulates the sympathetic nerve, and you may experience sweating, increase heartbeat, decrease blood pressure, fatigue, dizziness, and tremor.

 

 

Which drugs fall in oral hypoglycaemic agents for the treatment of diabetes?

The major drawback of insulin – it is given by injections. That’s why oral hypoglycaemic medicines are used in type-2 diabetes treatments. 

Oral hypoglycemic agents are also very effective in controlling high blood glucose levels. It works on type 2 diabetes. 

 

1. Insulin Sensitizers – 

Biguanides – Metformin

Everyone knows this drug which is the most commonly prescribed medication and the first choice among antidiabetic medicines while treating type-2 diabetes.

Metformin tablet works as –

  • Reduce gluconeogenesis. This means it decreases the absorption or formation of a new glucose molecule (e.g., protein) from the intestine. 
  • Reduce hepatic glycogenolysis. This means it decreases the breakdown of glycogen, which converts into glucose and decreases glucose transport from the liver to blood.
  • Reduce insulin resistance. Metformin activates insulin which helps to transports glucose molecules from blood to cell.

 

The main side effects of metformin are related to the stomach, which causes diarrhea, bloating, nausea, etc.

It also causes one dangerous side effect – lactic acidosis, which is rarely seen in patients. Lactic acidosis could be fatal if your kidney and liver are already compromised.

You should avoid metformin if your blood creatinine level more than 1.5 and abnormal liver function. 

You should also avoid metformin if you are pregnant. In that case, insulin injection is the safest option.

Metformin is available in the form of normal release, extended-release, and sustains release. The maximum dose of metformin 2.5 gm/day.

 

 

 Thiazolidinediones (gltazones family) – 

Glitazones are the second or third-line treatment of type 2 diabetes. It includes rosiglitazone and pioglitazone.

But currently, only pioglitazone is available. Rosiglitazone is banned in many countries due to its life-threatening risk.

Rosiglitazone is banned in India since 2010. These drugs are also withdrawn from some European countries like Germany and France due to increased risk of bladder cancer, myocardial infarction, congestive heart failure, stroke, and death.

Due to these high risks, US FDA restricted the use of glitazones. If we see the mechanism of glitazones. These drugs help to decrease insulin resistance. 

It works on the nuclear receptor, which stimulates peroxisome proliferator-activated receptor (PPAR gamma) mostly in fat cells. It alters the transcription of several genes and enhanced GLUT4 expression that improves glucose entry into fat cells.

The most common side effects of glitazones are fluid retention. You may notice swelling in your ankles if you are on these drugs. 

You should avoid these glitazones if you have a history of heart disease and significant kidney or liver problems.

 

 

2.Insulin secretagogues – 

a) Sulfonylureas (Glipizide, Glimepiride, Glyburide) and Meglitinides ( Repaglinide, Nateglinide)

Sulfonylureas and meglitinide have the same mode of action. These drugs stimulate beta cells which helps in the release of your insulin. These drugs inhibit the ATP-sensitive K+ channel in the beta cell of the pancreatic islets.

This means it decreases the outflux of K+ ions. Along with that, it increases the intracellular Ca+2 ions by open the Ca+2 channel, resulting in the exocytosis of store insulin and insulin release.

You should take these drugs 30 minutes before each meal. The main side effects of these drugs are hypoglycemia, and it should be avoiding those patients who have a history of liver or kidney problems.

 

b) DPP-4 inhibitors –

In diabetes, incretins hormones are destroyed by a dipeptidyl peptidase-4 enzyme which retards insulin secretion. These drugs help inhibit the dipeptidyl peptidase-4 enzyme and help to reduce blood glucose levels, especially after a meal.

There are some examples of DPP-4 inhibitors – sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Trajenta), and Vildagliptin (Galvus).

Sitagliptin may be used with a combination of other antidiabetic drugs like metformin, sulfonylureas, meglitinides, glitazones, and insulin. 

It may cause hypoglycemia if it is given in combination with other diabetic drugs.

 

3. Others 

Alpha-glucosidase inhibitors – The main side effect of these drugs is flatulence. Because these drugs help delay the digestion and absorption of starch or glucose by inhibiting intestinal digestive enzyme alpha-glucosidase. 

Examples are acarbose, voglibose, and miglitol. 

 

 

How does the physician decide a treatment plan for diabetes?

There are some basic guidelines for the management of diabetes. In the case of type 1 diabetes, it can be managed by diabetic diet + exercise + insulin.

But if you are dealing with type 2 diabetes, sometimes diet and exercise will not be enough to control your blood sugar. 

It can be seen many prescribers start the treatment with single medicine, which is known as metformin. 

If it is not enough to control your diabetes, prescribers may add some other drugs like sulphonylureas. Later on, it may add up to 3-5 more medicines. Eventually, it may go up to insulin injection.

 

Conclusion 

Life does not end with diabetes; it can be managed by proper diet and exercise. 

If it is not controlled with diet and exercise. Then antidiabetic medicines can play a significant role in managing your diabetes. But you should use these medicines under the supervision of your physicians. 

I hope this article – treatment of diabetes covers valuable information.

 

Sources –

1. D. Tripathi, Essentials of medical pharmacology, 7th Edition. Jaypee Brothers Medical Publishers (P) Ltd; 2013. Chapter – 19, Insulin, oral hypoglycemic agents and glucagon, Page – 258.

2. Diabetes education online, university of California. https://dtc.ucsf.edu/

3. Electronic medicines compendium (EMC) https://www.medicines.org.uk/emc

4. National clinical guidelines for management of diabetes mellitus, 2010, first edition.

5. Metformin SmPC, EMC

6.  https://pubmed.ncbi.nlm.nih.gov/11921433/

 

 

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