Diabetes: tablets for type 2 diabetes

Tablets that are used to treat type 2 diabetes mellitus are known as oral hypoglycaemics or antihyperglycaemics. They are generally not suitable for people with type 1 diabetes as these people must take insulin injections one or more times daily because their insulin-secreting pancreas cells have been destroyed.

There are a number of different types of oral hypoglycaemics available for treating type 2 diabetes, and they work in different ways. They may be used on their own and some can be used in conjunction with each other, or with insulin.

Biguanides

Metformin (e.g. Diabex) is the only biguanide currently available in Australia.

Metformin is a moderately effective antidiabetic agent, and is generally prescribed for overweight and obese people with type 2 diabetes, sometimes in conjunction with sulfonylureas. It is also commonly used in non-obese people. There are combination medicines that contain both metformin and another type of oral hypoglycaemic (see below) in one tablet. These include the medicines Glucovance (metformin plus glibenclamide, a sulfonylurea), Avandamet (metformin plus rosiglitazone, a glitazone), Janumet (metformin plus sitagliptin, an incretin enhancer) and Galvumet (metformin plus vildagliptin, another incretin enhancer).

How do they work?

Biguanides work by reducing the amount of glucose produced by the liver, increasing the uptake of glucose by muscle and fat cells, and slowing the absorption of glucose by the intestine. This in turn reduces the level of glucose in the bloodstream.

Side effects

Lactic acidosis
The most serious complication associated with metformin is lactic acidosis. This happens when lactic acid builds up in the body faster than it can be metabolised. It is a potentially fatal condition but is very rare. When it occurs in people treated with metformin it is generally associated with old age, or people with kidney, liver or heart problems, those taking more than 2 grams of metformin per day, or those drinking excessive amounts of alcohol. Anyone who may have lactic acidosis should be taken immediately to the nearest accident or emergency department or receive urgent medical attention. The symptoms of lactic acidosis are:

  • nausea, vomiting, stomach pain;
  • trouble breathing;
  • feeling weak, tired or generally unwell;
  • unusual muscle pain;
  • unusual sleepiness;
  • dizziness or light-headedness;
  • shivering, feeling extremely cold; and
  • slow heartbeat.

Other side effects
More common side effects include nausea and diarrhoea. Your doctor will minimise the chance of you getting these by making gradual adjustments to your dose and by advising that you take the tablets at mealtimes. Beneficial side effects of taking metformin that have been observed include weight loss, and improved lipid (cholesterol) profile. When used on its own, metformin rarely causes hypoglycaemia (blood glucose levels that are too low).

When should you take them?

In order to reduce unwanted gastrointestinal side effects, biguanides (metformin) should be taken with or at the end of a meal.

Sulfonylureas

Sulfonylureas include the medicines:

  • glibenclamide (Daonil, Glimel);
  • gliclazide (e.g. Diamicron);
  • glimepiride (e.g. Amaryl); and
  • glipizide (e.g. Minidiab).

There is also a medicine called Glucovance that contains both glibenclamide and metformin in one tablet.

The sulfonylureas are an older, but very effective, group of antidiabetic agents. They are usually prescribed for people with type 2 diabetes who are not obese.

How do they work?

Sulfonylureas work by helping to stimulate the release of insulin by the pancreas. They may also have some effect in improving the sensitivity of the body's tissues to the action of insulin and in reducing the production of glucose by the liver.

Side effects

Possible side effects of sulfonylureas include weight gain, skin rashes and gastrointestinal disturbances. They also increase the risk of hypoglycaemia, which can be life-threatening, particularly in elderly people or people with kidney or liver problems. Many other medicines can interact with sulfonylureas, so be sure to tell your doctor about any other medicines you are taking.

When should you take them?

Sulfonylureas should be taken at mealtimes to reduce the risk of hypoglycaemia.

Thiazolidinediones (glitazones)

Pioglitazone (e.g. Actos) and rosiglitazone (Avandia) are examples of another group of oral hypoglycaemic drugs called thiazolidinediones. These medicines may be used either on their own or in conjunction with other diabetes medicines.

There is a medicine called Avandamet that contains both rosiglitazone and metformin in one tablet. These combination tablets can be prescribed for people who are already treated with both rosiglitazone and metformin, or those whose diabetes is not adequately controlled on either rosiglitazone or metformin alone.

How do they work?

Thiazolidinediones work by increasing the sensitivity of the body's tissues to the action of insulin, rather than stimulating insulin secretion. This allows glucose to be transported from the bloodstream into the body's fatty tissue, skeletal muscle and liver cells more efficiently.

Side effects

Side effects of the thiazolidinediones include fluid retention, anaemia, increased risk of bone fracture in women, and raised lipid levels. They may also cause weight gain and heart problems, such as heart failure or a possible increased risk of heart attack (rosiglitazone). They are generally not prescribed for people who have heart failure or in the case of rosiglitazone, heart disease or angina.

When should you take them?

Thiazolidinediones are taken once or twice daily, with or without food. It may take 6 to 8 weeks to get the full effect of these drugs on blood sugar levels.

Alpha-glucosidase inhibitors

Acarbose (brand name Glucobay) is the only type of alpha-glucosidase available in Australia. Acarbose is sometimes prescribed in conjunction with biguanides or sulfonylureas.

How do they work?

The alpha-glucosidase inhibitors interfere with the function of some of the digestive enzymes (alpha glucosidases) that are involved in digesting carbohydrates. The effect is to slow carbohydrate digestion in the small intestine so that glucose (sugar) is not absorbed into the bloodstream so quickly. This decreases the blood glucose peaks which happen after a meal.

Side effects

Common side effects of alpha-glucosidase inhibitors include flatulence, diarrhoea and abdominal pain, especially upon initial treatment. However, starting at a low dose and gradually increasing it to the final dosage, rather than starting with the final dose, can help avoid these problems.

When should you take them?

Alpha-glucosidase inhibitors (acarbose) must be taken immediately before your meal, or with the first couple of mouthfuls, in order for them to work.

Glitinides

Repaglinide (NovoNorm) is an oral hypoglycaemic belonging to the glitinide group of drugs. It is sometimes prescribed for people who cannot adequately lower their blood glucose levels through diet alone. It is sometimes prescribed in addition to metformin tablets or sometimes with insulin therapy in people with type 2 diabetes.

How do they work?

Glitinides work by stimulating the pancreas to produce a surge of insulin just after eating. Because it works quickly, repaglinide gives you more freedom to determine when you want to eat than other diabetes medicines.

Side effects

Common side effects of glitinides include hypoglycaemia, gastrointestinal disturbances, skin rashes and raised lipid levels.

When should you take them?

You should take repaglinide just before eating to ensure that it works properly, and to help reduce the risk of hypoglycaemia.

Incretin enhancers and mimetics

These medicines include sitagliptin (Januvia), vildagliptin (Galvus) and most recently saxagliptin (Onglyza) — which are incretin enhancers — and exenatide (Byetta) - which is an incretin mimetic. Sitagliptin, vildagliptin and saxagliptin are oral medicines, while exenatide must be injected. These medicines are used in adults, and are used in combination with other oral diabetes medicines.

How do they work?

Incretin enhancers — also called dipeptidyl peptidase-4 (DPP-4) inhibitors — and incretin mimetics work by increasing the production and release of insulin by the pancreas, as well as by reducing the production of glucose by the liver.

Incretin enhancers and mimetics work when blood glucose levels are high, especially just after a meal, but also help to lower blood sugar levels between meals. On their own they are unlikely to cause hypoglycaemia, because they do not work when blood sugar levels are low.

Side effects

Side effects of incretin enhancers can include discomfort when swallowing, headache, cold-like symptoms (sitagliptin and saxagliptin), and dizziness and tremor (vildagliptin).

Side effects of exenatide can include nausea and, in a very small number of people, pancreatitis.

When should you take them?

The incretin enhancers are taken once daily (or sometimes twice daily for vildagliptan), with or without food. They are taken as combination therapy with metformin, a sulfonylurea or a thiazolidinedione. They should be taken around the same time each day.

Exenatide is injected twice a day, before breakfast and before dinner.

There is a medicine called Janumet that contains both sitagliptin and metformin in one tablet and another called Galvumet that contains both vildagliptin and metformin. These fixed-dose combination tablets can be prescribed for people who are already treated with both metformin and sitagliptan or vildagliptan, respectively, or those whose diabetes is not adequately controlled on metformin alone. Janumet and Galvumet should be taken twice a day with meals.

Long-term outlook for people taking tablets for type 2 diabetes

It is not unusual for oral hypoglycaemics to control type 2 diabetes for a number of years, and then stop working. In fact, insulin treatment may be required in one-third of people with type 2 diabetes after 10-15 years of successful management using oral hypoglycaemic agents.

A healthy balance

Regardless of the type of diabetes you may have, it is important to recognise that medicines are only part of the overall treatment picture. It is just as important to follow both a healthy eating plan and a regular activity programme in order to maintain relatively stable blood glucose levels.


 
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