Diabetes Medications -- Insulin and Other Injectables

By Emeritus Professor Datuk Dr. Mustaffa Embong, Consultant Diabetologist

The writer Emeritus Professor Datuk Dr Mustaffa Embong is consultant diabetologist at the National Diabetes Institute (NADI). This is the second of his series of articles on medications for people with diabetes.

KUALA LUMPUR (Bernama) -- In the previous write-up on medications for people with diabetes, we talked about the use of oral medications (tablets) for the treatment of diabetes as an addition (not a replacement) to a healthy diet and regular physical activity.

In this article, we will discuss briefly the use of insulin and other injectables in the treatment of both type 1 and type 2 diabetes. We will also touch on other medications usually prescribed for people with diabetes.

WHAT IS INSULIN?

Insulin is a hormone produced by beta cells in the pancreas, an organ situated behind the stomach. Its main function is to help glucose from the circulation to enter the body cells to be used as energy.

Insulin is released into the bloodstream in response to the food we take. Some background insulin is still present when we are not eating in order to maintain blood glucose level as glucose may still be produced by our liver.

In people with type 1 diabetes, the body produces little or no insulin as the beta cells that make insulin have been destroyed by an autoimmune reaction. 

In those with type 2 diabetes, the body still produces insulin but it is not enough as the body does not respond well to its action – a condition referred to as insulin resistance.

Properly used, insulin is effective and safe and most types can be used in women who are pregnant or breastfeeding.

INSULIN USE IN PEOPLE WITH DIABETES

As expected, type 1 individuals will require insulin replacement (to live). People with type 2 may also be given insulin in acute situations such as when having ketoacidosis or an infection or when undergoing a major operation and during pregnancy.

Occasionally insulin is also prescribed to ‘rest’ the beta cells, usually at diagnosis and when symptoms are severe.

But, in type 2 diabetes, insulin is mostly used because of beta-cell failure. Type 2 diabetes is known to be a progressive condition with decreasing insulin production over time due to beta cell dysfunction/death. 

And, after 10 to 20 years of diabetes, 50 to 70 percent of people with type 2 diabetes are expected to require insulin (usually in addition to tablets) to properly control their blood glucose levels.

TYPES OF INSULIN

Most types of insulin available in Malaysia now are synthesised based on human insulin gene (‘human insulin’). The human insulin has also been modified to produce insulins with unique characteristics (‘analogue insulin’).

Insulins are classified based mainly on their duration of action – classically as short-, medium- and long-acting insulins (see Table 1)  

Table 1: Types of insulin

 

Type (based on action)	Duration of Action*	Examples
Fast acting Insulin (analogue)	3-6 h (onset 10-20 min;  peak 1-2 h)**	‘Humalog’ (Lispro), ‘Novorapid’ (Aspart), ‘Apidra’ (Glulisine)
Short acting Insulin (human)	6-8 h (onset 30-60 min; peak 2-4 h)**	‘Humulin R’, ‘Actrapid’
Medium acting insulin (human)	12-24 h (onset 2-4 h; peak 4-8 h)**	‘Humulin N’, ‘Insulatard, NPH insulin
Long acting insulin (analogue)	24-36 h (onset 1-2 h; minimal peak)	‘Lantus’ (Glargine), ‘Levemir’ (Detemir,) ‘Toujeo’ (Glargine                U-300)
Ultra-long acting insulin (analogue)	About 42 h (onset 1-4 h; No significant peak	‘Tresiba’ (Degludec)
Pre-mixed insulin	12-24 h (onset variable)	‘Mixtard 30’, ‘Humulin 30/70’, ‘NovoMix 30’, ‘Ryzodeg’

 * approximate; ** from time of injection

HOW INSULIN IS USED

Currently, insulin can only be given by injection (even though trials are being undertaken to give insulin via spray or in tablet form). Insulin is injected through the skin into the fatty tissue known as the subcutaneous layer (not into muscles or blood vessels). The usual sites for injection are the tummy (abdomen), upper arms, buttocks and thighs. Your diabetes educator will teach you how and where to safely inject your insulin.

The number of times you have to inject your insulin would depend on many factors, including the type of diabetes you have, the severity of insulin deficiency and the type of insulin you use (and your preference).

The preferred dosing is to mimic the physiological insulin release in people without diabetes where insulin release spikes when food is being eaten and minimal insulin is released when food is not being consumed (for example, when one is asleep) to cover for the glucose released from the liver.

Thus, people with type 1 diabetes (for example, children) and those with type 2 diabetes who lack insulin (for example, due to long-standing diabetes) ideally will take a fast-acting insulin (meal-time insulin) before each main meal and another injection of long-acting insulin (called basal insulin) before going to bed.

Administering an insulin injection is easy and very convenient now as most preparations are provided as disposable penfills (with fine needle) which can be carried around in a shirt pocket or purse. Your doctor will, of course, choose the most suitable insulin regimen for you and determine the correct dose to bring your blood glucose to the recommended levels.

As insulin is very powerful in bringing the blood glucose down, there is the tendency for you to develop hypoglycaemia (low blood glucose level or 'hypo') if you happen to inject too much insulin or do not take your meals on time (or perform strenuous exercise).

For this reason, people on insulin must do blood glucose tests regularly at home using a portable glucometer. Blood glucose is usually tested on waking up in the morning ('fasting'); two hours before and after a main meal; before going to sleep; before, during and after exercise; and at any time you do not feel well.

Your doctor will advise you on the number of tests that you need to do and the timing. Always record the results and bring them to the clinic to discuss with your doctor or your diabetes educator. For this reason too, you must know the early symptoms of ‘hypo’ and how to abort it effectively.

GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS

A new group of injectable drugs called glucagon-like peptide-1 receptor agonists (GLP-1 RA) is now available in Malaysia (see Table 2). GLP-1 RA, in a specific prefilled pen device (and administered subcutaneously like insulin) is used for the treatment of type 2 diabetes by patients who are not well-controlled when it comes to taking tablets.

It works by mimicking the functions of the natural incretin hormones in your body that help to lower blood glucose levels after food, as well as stimulate the pancreas to release insulin, inhibit the release of glucagon (a hormone that stimulates the liver to release glucose) and slow down the stomach emptying process after eating (making you feel full for a longer period of time after a meal).

Table 2: Types of Glucagon-like peptide-1 receptor agonists

Name	Frequency of Injection	Examples
Exenatide	Twice daily	‘Byetta’
Liraglutide	Once daily	‘Victoza’
Dulaglutide; Exenatide extended release	Once weekly	‘Trulicity’; ‘Bydureon’

Other than improving diabetes control, glucagon-like peptide-1 receptor agonists are also known to cause weight loss when used in combination with diet and exercise.

As such, it is usually used in people with type 2 diabetes who are also overweight or obese. Weight loss in these individuals would also improve their blood glucose levels.

GLP-1 RA is also useful in those with type 2 diabetes who are prone to having low blood glucose levels as the drug does not normally cause hypoglycaemia.

One of the drawbacks in using glucagon-like peptide-1 receptor agonists is their common adverse effects on the gastrointestinal tract: GLP-1 RAs tend to cause nausea, vomiting and diarrhoea especially at the beginning of treatment. As such, your doctor may advice you to start on a lower dose and to increase the drug slowly to reduce these side-effects. 

OTHER MEDICATIONS TO TAKE

People with diabetes often also have high blood pressure and abnormal blood fat (‘cholesterol’) levels that can increase the risk of diabetic complications such as heart attack, stroke or kidney failure. Your doctor may prescribe medications to control these abnormalities:

Drugs to lower your blood pressure

Drugs called angiotensin-converting enzyme inhibitors (ACE-I) (eg., ‘Coversyl’) or angiotensin receptor blockers (ARBs) (eg., ‘Cozaar’) are commonly prescribed to control blood pressure in people with diabetes. Other drugs such as beta blockers (eg., ‘Metoprolol’) and calcium channel blockers (eg., ‘Norvasc’) may also be given in combination with an ACE-I or ARB to better control your blood pressure.

Drugs to control your blood cholesterol

Statin (for example, ‘Lipitor’) is the most common drug group prescribed to lower high blood cholesterol level. Your doctor may prescribe another cholesterol-lowering medication (for example, ‘Fenofibrate’) if you are intolerant to statin. Sometimes, you have to take more than one kind of cholesterol-lowering drugs to achieve your cholesterol targets.

Drugs to make your blood less sticky

Studies have shown that taking low-dose aspirin every day can help reduce the risk of heart attack and stroke. Aspirin – the most commonly-used (and the cheapest) – makes blood particles (called platelets) less sticky. However, aspirin is not safe for everyone because of possible allergy or bleeding from the stomach. Check with your doctor if you have to take aspirin. Your doctor may prescribe an alternative blood-thinning medicine (for example, ‘Plavix’) if you are allergic to aspirin.

CONCLUSION

Your doctor will determine the best type of oral medication or injection for you and whether you need only one type or a combination of drugs (including insulin or other injectables) to achieve your blood glucose targets (and for other associated conditions such as high blood pressure or abnormal blood fats).

It is also important to stress that you must always take the medications as prescribed by your doctor. Please do not change the dose (or frequency) without first consulting your doctor. Do inform him/her if you are not comfortable with a medication (due to its side-effects or cost) as an alternative is usually available.

Your doctor and your diabetes management team are there to help you achieve your health targets – for you to remain healthy and free of complications. Please make it a point to always discuss with them if you have a problem regarding your treatment.

But, ultimately your (good) health is in your hands: your doctor or healthcare team can only advice you (over a few minutes) once in a few months. You are on your own for the rest of the days and months (before the next clinic visit).

To ensure good health (in spite of your diabetes), you must be disciplined and make a firm commitment to look after your health by keeping to a healthy lifestyle and taking the medications as prescribed (and follow the advice given) by your doctor. We are confident you can do this – for your own sake and that of your loved ones.

Edited by Rema Nambiar

-- BERNAMA