Tablet treatment

There are six main kinds of tablet treatment for people with type 2 diabetes:

1 sulphonylureas

2 biguanides

3 acarbose

4 thiazolidinediones

5 glitinides

6 gliptins.

They all come under the general name of oral hypoglycaemic agents (OHAs), and any of them may be taken alone or in combination. Most people with type 2 diabetes find that these medications, together with a healthy eating pattern, keep their diabetes well under control, although it may take a while to find out which combination or dose suits them best. However, with the passage of time, patients can gradually lose their responsiveness to the tablets and blood glucose levels rise to the extent that insulin injections are needed.
If you do experience side effects or find that your blood glucose levels are higher than they should be, you should go back to your GP to discuss possible changes to your treatment.

Sulphonylureas

Sulphonylureas (SUs) work by stimulating the pancreas to release stored insulin. You could say that they raise the insulin level by proxy, and so help to keep blood glucose down. You have to remember that, although you’re not actually taking insulin, these tablets have a similar effect because they increase the amount of insulin in your bloodstream, and it is possible for it to increase too much. If this happens, your blood glucose levels will drop too far, and you may sometimes experience the symptoms of hypoglycaemia (too little glucose in the blood, see page 76). To prevent this happening, you should make sure that you eat regularly, and take your tablets either with or just before a meal.
As with insulin, SUs can be short, medium or long acting (see below), and must be taken once, twice or three times a day depending on how fast they work. The long-acting versions do not always suit older people or those whose lifestyle makes it difficult to have regular mealtimes because of the risk of hypoglycaemia.

Side effects

Apart from having to be aware of the risk of low blood glucose (hypoglycaemia), most people taking SUs findthat they have few, if any, serious side effects. Probably the most annoying one is that some patients find that their faces can get very flushed and hot when they drink alcohol. The precise reasons for this side effect are unclear.
As you’ll soon discover once you’re taking them, the fact that SUs lower your blood glucose will make you feel very hungry so you could gain a lot of weight if you’re not careful.
A minority of people won’t be able to take SUs because they’re allergic to them, and if you’re allergic to the antibiotic Septrin you may also have a reaction to SUs.

Names of sulphonylurea tablets available in the UK

Biguanides

This type of drug has been in use for over 50 years, and the only one available in this country is metformin. No one is sure precisely how it works, but it seems to slow down the absorption of glucose from the intestines, reducing the blood surge after a meal, and it may also have a more complicated effect on the liver.
As a result of this, you can’t take it if you have any kind of liver disease, and it is also best avoided in patients with kidney complications (see page 113). You don’t have to worry about your blood glucose level dropping too far when you’re on metformin because it doesn’t stimulate the release of insulin.
It’s often prescribed for people who are overweight because it doesn’t make you feel hungry or put on extra pounds. You normally start on a low dose, taking it once or twice a day with meals, and then gradually build up the amount that you’re taking as you get used to it.

Side effects

The main side effects are stomach upsets – nausea and diarrhoea – and some people have to stop taking it because of this problem.

Acarbose

This works in quite a different way from the other OHAs. By interfering with the breakdown of carbohydrates in the intestine, it stops your body from absorbing glucose from food.
Unfortunately, this means that more sugars remain unabsorbed in the large intestine where lots of bacteria and micro-organisms lurk. These feed on the abundant sugar and proliferate, which can mean that you suffer from loose motions and flatus (wind). Nevertheless, it could be the right option for you if you find it difficult to follow a healthy eating plan or tend to be overweight.

Thiazolidinediones (glitazones)

Thiazolidinediones increase the sensitivity of cells to the effects of insulin. Rosiglitazone and pioglitazone are licensed for use in the UK. They are usually used with either an SU or metformin and, although they do not cause hypoglycaemia directly, they can produce it in combination with SUs.
The most common side effects are weight gain and fluid retention. Extensive clinical trials are ongoing.
These tablets have been licensed for use on their own and are available in a single-tablet combination with metformin. Scientists reviewing the results of large trials of these medicines have found that they may cause osteoporosis (thinning of the bones) and predispose to fractures. Rosiglitazone has also been linked to heart attacks and some doctors suggest that it should not be used in people with known heart disease.

Glitinides

Two of these tablets are available in the UK (repaglinide and nateglinide). They are taken immediately before meals and lower glucose by stimulating insulin release. However, because of their short action they are thought to be less likely to produce hypoglycaemia than conventional SUs.

Gliptins

Two new drugs, vildagliptin and sitagliptin, are now available. They work by preventing the breakdown of glucagon-like peptide 1 (GLP-1), which is a hormone released by the intestines in response to food. GLP-1 is a powerful stimulant for insulin release from the pancreas. Short-term trials show promising results but longer-term studies are awaited.

Incretins

Research using a form of GLP-1, called exenatide, has found it to be very effective at both lowering blood glucose and losing weight. Its drawback is that it has to be given by injection, twice a day, although a longer-acting weekly preparation is undergoing research. Exenatide is now available in the UK. Its main side effect is stomach upset (nausea and sickness). An alternative preparation called liraglutide, which is a once-daily injection, will soon become available in the UK.

When you need insulin

When you have type 1 diabetes, there’s no alternative to replacing the missing insulin by means of daily injections. People whose diabetes is not effectively controlled by diet and tablets may also have to change to insulin injections.
If you’ve just found this out, it’s bound to take you a while to adjust to the idea but, with the right information and back-up from your diabetes care team, you’ll soon realise that you will be able to cope and keep yourself well. They will show you how to give injections, and take time to teach you how to manage your condition effectively.
Don’t worry if you need to see them several times to get things clear – no one will mind. In fact, they will encourage you to keep asking questions and coming back until you feel comfortable with all the masses of new information. Here are some of the questions that people with newly diagnosed diabetes ask most often.
 

Why inject the insulin?

This is the only effective way of getting it into your bloodstream. If you swallow it, it is partly digested and so becomes less active, which means that it can’t do its job of controlling your blood glucose level. Although other ways of giving insulin have been tried, they’ve all had problems, so injection is the only practical option for the time being.

Why is insulin injected under the skin?

In theory, it could be injected into a vein or a muscle, as happens with some other medicines such as antibiotics. In practice, however, injecting the insulin into a vein several times a day would be difficult, and intramuscular injections can be painful. Both these methods are sometimes used in special circumstances – for instance when you are ill or can’t eat regularly, perhaps because you’re having an operation.

What types of insulin are there?

The basic difference is in how quickly they take effect, so that they can be divided into short-, medium- or long-acting varieties. The short-acting insulin is always clear or colourless, whereas the other two are usually cloudy because they contain additives to slow down the absorption of insulin from under the skin. It is possible to mix short- and medium-acting insulins in the same syringe, but care must be taken not to contaminate the clear insulin with any cloudy insulin. For this reason the clear insulin is always drawn up first.
If you find it difficult to mix insulins yourself, you may be able to use one of the ready-mixed kinds that contain quick- and medium-acting insulins in different proportions.

Where does this insulin come from?

All three types of insulin may be produced from animal sources – pig or beef – or from genetically engineered human hormone. Recently, scientists have been able to create modified insulins using the new genetic technology. These insulins, called analogues, are absorbed either more quickly or more slowly and smoothly.
Quick-acting analogues (Humalog or NovoRapid) can be injected immediately before, during or even after a meal, and are therefore more convenient to
use, particularly for people with variable mealtimes. They also enable you to have a bit more insulin if the meal was larger than expected.
The only long-acting analogues available in the UK at the moment are glargine and detemir. These insulins can be given once or twice daily at any time but
preferably at the same time each day. Unlike other long-acting insulins, glargine and detemir are clear solutions and care must be taken not to confuse them with fast-acting preparations.
Detailed research trials are ongoing to discover the best way of using these new insulins, but early results suggest that analogues may be associated with less
hypoglycaemia.

Is human insulin better than pig or beef?

This is a controversial area and some patients who changed from animal to human insulin have said that they feel less well since the switch. It seems that human insulin is absorbed slightly more quickly from under the skin.
However, no measurable differences in blood glucose levels have been found when human and animal insulins were tested under control conditions, but some people do prefer the animal preparations. At the moment supplies are still available and said to be guaranteed for the foreseeable future.

Why do I have to inject insulin several times a day?

The object of insulin therapy is to imitate the body’s natural supply as closely as possible. In a person who doesn’t have diabetes, insulin is released by the pancreas in response to food (see diagram on page 56). As the blood glucose level falls between meals, so the insulin level drops back towards zero. It never quite gets there, however, and there is no time in the 24 hours when there is no detectable insulin in the bloodstream. What you are trying to do when you give yourself insulin injections is to reproduce the normal pattern of insulin production from the pancreas.
There are several ways of doing this using different types of insulin and numbers of injections per day. For example, many people follow a system of injections of short-acting insulin before the three main meals of the day, plus a night-time injection of a medium- or long-acting insulin to control blood glucose while they’re asleep.
Another popular and equally successful system involves two injections a day of a mixture of short- and medium-acting insulins. The idea is that the short-acting component covers the meal that you’re about to have (say breakfast or tea/evening meal), while the medium-acting component covers you at lunchtime or overnight. Many people have been using one or other of these systems very happily for years, and the choice between them is often simply a matter of personal preference.
If you’re one of the relatively few people who simply can’t get used to giving themselves several injections a day, or if you have only a partial failure of your insulin supply, you may be able to make do with just one or two daily injections of medium- or long-acting insulin.

How and where do I inject myself?

Your diabetes care team will show you how to do the injections and explain the various types of equipment available. Most people today use disposable plastic syringes and needles.
Disposable syringes and needles can be used several times with little risk of infection. They are usually thrown away when the needle becomes blunt and injections become less comfortable.
Insulin injection pens are very popular, largely because of their convenience and portability. The pens themselves and the needles are available on prescription. There are several types of pen to choose from, but the principles of the device are much the same. It’s simply a matter of which one suits you best.
As we’ve already seen, you inject insulin under your skin rather than into a vein or muscle. Recent research has suggested that many people may have been getting the depth wrong so that insulin is going into the muscle beneath the skin by mistake.
Judging the depth accurately can be quite difficult, especially if you’re slim, but it’s important to master the technique because insulin can be absorbed from
muscle more rapidly than expected.
Your diabetes care team will show you how to do it properly, but a lot of people find that the simplest way is to inject at an angle of 90 degrees. There is a range of different length pen needles now available so it is easier to control the depth of injections. It is important for you to find the right type of needle depending on your injection site and body size. This needs to be
discussed with your diabetes care team.
You’ll be given advice about the best sites for injection (see figure opposite). The tops of the thighs, buttocks and abdomen are the most common sites, and it’s best to avoid using the same area every time, otherwise you could develop a small fatty lump (called lipohypertrophy) which could affect the smoothness of insulin absorption. It’s probably a good idea to inject medium- or longer-acting insulins into your thigh or buttock and use your tummy for quick-acting injections, but the most important thing is that you should be happy about the sites that you’re using.

Will the injections hurt?

People who’ve been giving themselves injections for years say that they don’t feel a thing, but many beginners may find it slightly painful at first. Try to be as relaxed as you can and follow the technique that you’ve been shown. Some people find that it helps to rub the skin with ice for a few seconds beforehand to numb it, and you might like to give this a try.
As you get more practice, you should find that the injections rarely hurt, but, if things don’t improve, it’s worth asking someone at the diabetes care centre for advice on what’s causing the problem.

Will the injections leave a mark?

The needles are very fine and usually do not leave a mark. Sometimes you may get a little bleeding after an injection or even a bruise, but this is nothing to worry about. It just means that you’ve probably punctured one of the tiny blood vessels under the skin, and this happens from time to time. There is virtually no chance of insulin directly entering the bloodstream, so don’t worry if you notice some bleeding.

Can you give insulin by other routes?

Until recently, inhaled insulin was available. It required a rather large device, which was much bigger than an asthma inhaler. Insulin given this way is no more effective than by injection, and you would still need to inject overnight insulin because only short-acting preparations can be inhaled.
Although there have been no safety concerns so far, long-term effects on the lungs cannot be completely ruled out. Finally, inhaled insulin was wasteful, needing 10 times the dose used by injection, and it was expensive. It was probably most useful if you were needle phobic and could not contemplate injections, and definitely needed insulin for your diabetes control.
Unfortunately the only supplier has recently withdrawn its product from the UK.

Can you take insulin and tablets at the same time?

Some type 2 patients who need insulin and are also insulin resistant can benefit from a combination of injections and metformin. Increasingly, doctors prescribe a combination of long-acting insulin and an SU or glitinide before meals.

What about an insulin pump?

Some patients have found that giving insulin by a constant infusion under the skin via a thin plastic tube and needle gives smoother blood glucose control. Pumps therefore require a lot of input from the patients who use them. They may be particularly effective in young children who struggle with multiple injections. Pumps are expensive (around £2,800) and cost more than £1,000 every year to run. They also require considerable medical expertise as back-up.
The National Institute for Health and Clinical Excellence (NICE; see ‘Useful addresses’, page 149) has approved insulin pump therapy for patients with type 1 diabetes who find it difficult to achieve satisfactory blood glucose control without experiencing hypoglycaemia. Their advice was revised in 2008 and is available on the website.
Specialised diabetes units have been set up around the UK. Funding should now be available. To check the situation in your district, contact your diabetes care team.
It is hoped that the ‘postcode lottery’ for pumps should soon become a thing of the past.

KEY POINTS

• Tablet treatment is useful for type 2 patients

• Tablets work in different ways and have different side effects. Be sure to check these with your diabetes care team when they are prescribed

• Insulin injections are necessary for all patients with type 1 and many with type 2 diabetes

• At least two and maybe four injections of insulin are needed a day

• Injections rarely cause discomfort or leave any mark

• Insulin preparations can be short, medium or long acting

• Pre-mixed short- and medium-acting preparations are now available

• A combination of insulin and tablets may suit some patients with type 2 diabetes

• Insulin pumps are increasingly available and may be particularly useful for children or those with troublesome hypoglycaemia