Diabetes: tablets for type 2 diabetes

Tablets that are used to treat type 2 diabetes mellitus are known as oral hypoglycaemics (meaning glucose lowering medicines) or antihyperglycaemics (meaning stopping high blood glucose levels).

There are a number of different types of tablets available for treating type 2 diabetes, and they work in different ways to help control blood sugar levels. They may be used on their own and some can be used in conjunction with each other, or with insulin.

Tablets are for people with type 2 diabetes whose blood sugar levels cannot be controlled with diet and exercise alone. They can help control your blood sugar levels and prevent diabetes complications. But tablets are not a magic bullet - you need to keep up with a healthy lifestyle.

Biguanides - metformin

Metformin (e.g. Diabex, Diaformin, Glucophage) is the only biguanide medicine currently available in Australia. It has been around for a long time and is still the first choice medicine prescribed for most people with type 2 diabetes. That’s because it is very effective and well tolerated by most people.

There are several combination medicines that contain metformin plus another type of oral hypoglycaemic medicine in one tablet. These include:

  • metformin plus a sulfonylurea — glibenclamide (brand name Glucovance);
  • metformin plus a glitazone — rosiglitazone (brand name Avandamet);
  • metformin plus a gliptin - sitagliptin (brand name Janumet), vildagliptin (brand name Galvumet), saxagliptin (brand name Kombiglyze), alogliptin (Nesina Met) and linagliptin (brand name Trajentamet); and
  • metformin plus a SGLT2 inhibitor - empagliflozin (brand name Jardiamet) and dapagliflozin (brand name Xigduo).

How does metformin work?

Metformin works in 3 ways to reduce the level of glucose in the bloodstream. It:

  • reduces the amount of glucose released by the liver;
  • increases the uptake of glucose by muscle and fat cells; and
  • slows the absorption of glucose by the intestine.

Side effects of metformin

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.

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.

People who have the highest risk of developing lactic acidosis while taking metformin include:

  • older people;
  • people with kidney, liver or heart problems;
  • those taking more than 2 grams of metformin per day; and
  • those who drink excessive amounts of alcohol.

People with severe kidney problems (renal failure) should not take metformin.

Anyone who may have lactic acidosis should be taken immediately to the nearest accident or emergency department to receive urgent medical attention.

More common side effects of metformin 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 (in overweight people), and improved lipid (cholesterol) levels.

When used on its own, metformin rarely causes hypoglycaemia (blood glucose levels that are too low).

When should you take it?

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

Sulfonylureas

The sulfonylureas are another older, but very effective, group of antidiabetic medicines. They are usually prescribed in combination with metformin, or can be taken as an alternative to metformin. Sulfonylureas include:

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

A combination medicine is available that contains both glibenclamide and metformin in one tablet (brand name Glucovance).

How do sulfonylurea medicines 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 of sulphonylureas

These medicines increase the risk of hypoglycaemia (low blood sugar) more than any other tablets for type 2 diabetes. Hypoglycaemia can be dangerous, particularly in older people or people with kidney or liver problems.

Other possible side effects of sulfonylureas include weight gain, skin rashes and gastrointestinal disturbances (such as nausea or diarrhoea).

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 sulfonylurea medicines?

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

Dipeptidyl peptidase-4 (DPP-4) inhibitors

Dipeptidyl peptidase-4 inhibitor (DPP-4i) medicines — also called incretin enhancers, or gliptins — are a newer type of tablet used to treat type 2 diabetes. These medicines are used in adults.

Gliptin medicines available in Australia include:

  • sitagliptin (Januvia);
  • vildagliptin (Galvus);
  • saxagliptin (Onglyza);
  • alogliptin (Nesina); and
  • linagliptin (Trajenta).

Gliptins are usually taken as combination therapy with other diabetes medicines.

Gliptins available as a combination medicine with metformin include:

  • sitagliptin plus metformin (brand name Janumet);
  • vildagliptin plus metformin (brand name Galvumet);
  • saxagliptin plus metformin (Kombiglyze);
  • alogliptin plus metformin (Nesina Met); and
  • linagliptin plus metformin (Trajentamet).

These fixed-dose combination tablets can be prescribed for people who are already treated with both metformin and an incretin enhancer, or those whose diabetes is not adequately controlled on metformin alone.

Gliptins are also available in combination with SGLT2 inhibitors, including:

  • saxagliptin plus dapagliflozin (brand name Qtern); and
  • linagliptin plus empagliflozin (brand name Glyxambi).

Incretin mimetics (also called GLP-1 receptor agonists) are a similar type of medicine for type 2 diabetes. But while the incretin enhancers are available as tablets, incretin mimetics must be injected. GLP-1 agonists that are injected once or twice daily include:

  • exenatide (brand name Byetta); and
  • liraglutide (brand name Victoza).

Long-acting GLP-1 agonists that are injected once a week include:

  • exenatide (brand name Bydureon);
  • dulaglutide (brand name Trulicity).

How do gliptins work?

Gliptins increase the production and release of insulin by the pancreas. They do this by enhancing the effects of the so-called incretin hormones made in the intestine - hence the name incretin enhancers. Gliptins also inhibit the production of glucose by the liver.

Gliptins work when blood glucose levels are high, especially just after a meal, but also help to lower blood sugar levels between meals.

Side effects of gliptins

Side effects can include:

  • headache;
  • cold-like symptoms; and
  • dizziness and tremor (vildagliptin).

Pancreatitis (inflammation of the pancreas) is an uncommon side effect of incretin enhancers and mimetics. These medicines need to be stopped if pancreatitis occurs.

When should you take gliptins?

These medicines are taken once daily (or sometimes twice daily for vildagliptin), with or without food. They should be taken around the same time each day.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors

Another newer type of medicine for type 2 diabetes are sodium-glucose co-transporter 2 inhibitors - SGLT2 inhibitors or flozins. These include:

  • dapagliflozin (brand name Forxiga); and
  • empagliflozin (brand name Jardiance).

These medicines are usually used in combination with other tablets for type 2 diabetes. They are available in combination with metformin:

  • dapagliflozin plus metformin (brand name Xigduo); and
  • empagliflozin plus metformin (brand name Jardiamet).

They are also available combined with DPP-4 inhibitors (gliptins):

  • dapagliflozin plus saxagliptin (brand name Qtern); and
  • empagliflozin plus linagliptin (brand name Glyxambi).

How do SGLT2 inhibitors work?

SGLT2 inhibitors act on the kidneys to increase the amount of glucose that is excreted in the urine, lowering the blood glucose level.

These medicines may also have other beneficial effects on blood pressure and weight. Empagliflozin may reduce the risk of developing heart disease associated with diabetes.

Side effects of SGLT2 inhibitors

Side effects include an increased risk of:

  • dehydration;
  • low blood pressure; and
  • genital and urinary tract infections.

Long-term side effects are still uncertain because these medicines are relatively new, but may include increased risk of bone fractures. Ketoacidosis is another rare but possible side effect.

When should you take them?

SGLT2 inhibitors should be taken once daily. These medicines are not prescribed on their own, but are used in combination with other medicines.

Alpha-glucosidase inhibitors - acarbose

Acarbose (brand name Glucobay) is the only type of alpha-glucosidase available in Australia. Acarbose can be used on its own or prescribed together with metformin or sulfonylureas.

How does acarbose work?

Acarbose interferes with the function of some of the enzymes (alpha glucosidases) 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 that happen after a meal.

Side effects of acarbose

Common side effects include flatulence, diarrhoea and abdominal pain, especially when treatment is first started. However, starting at a low dose and gradually increasing can help avoid these problems.

When should you take acarbose?

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

Thiazolidinediones (glitazones)

The thiazolidinediones, also known as TZDs or glitazones, are a newer type of oral hypoglycaemic. There are 2 glitazone medicines:

  • pioglitazone (brand name Actos, Vexazone); and
  • rosiglitazone (not available on its own).

A combination medicine that contains rosiglitazone and metformin in one tablet is available (brand name Avandamet). Pioglitazone is also usually prescribed in combination with other tablets for type 2 diabetes.

How do glitazones work?

These medicines 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, muscle and liver cells more efficiently.

Side effects of glitazones

Side effects can include:

  • fluid retention;
  • anaemia;
  • muscle pain;
  • increased risk of bone fracture in women;
  • raised lipid (cholesterol) levels (rosiglitazone);
  • weight gain; and
  • heart problems, such as heart failure or a possible increased risk of heart attack (rosiglitazone).

Pioglitazone is also associated with an increased risk of bladder cancer, with the risk increasing the longer you take it.

They are generally not prescribed for people who have heart failure or in the case of rosiglitazone, heart disease or angina. People with liver disease should not take glitazones.

When should you take glitazones?

These medicines are taken once or twice daily, with or without food. It may take 6 to 8 weeks for these medicines to have their full effect on blood sugar levels.

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. That’s because these medicines work by enhancing the effects of insulin, and as the amount of insulin made by the pancreas decreases over time, they become less effective. In fact, insulin treatment may be needed in about half of people with type 2 diabetes within about 10 years from the time of diagnosis.

Insulin and tablets for type 2 diabetes can be used together to control blood sugar levels.

A healthy balance

Remember, medicines are only part of the overall treatment for diabetes. It's just as important to follow both a healthy eating plan and a regular activity programme in order to maintain relatively stable blood glucose levels.

References

1. Royal Australian College of General Practitioners (RACGP); Diabetes Australia. General practice management of type 2 diabetes; 2016-18. https://static.diabetesaustralia.com.au/s/fileassets/diabetes-australia/5d3298b2-abf3-487e-9d5e-0558566fc242.pdf (accessed Aug 2018).
2. Diabetes Australia. Tablets: Medication for type 2 diabetes. https://www.diabetesaustralia.com.au/tablets (accessed Aug 2018).
3. NPS Medicinewise. Medicines and type 2 diabetes (published 20 Apr 2017). https://www.nps.org.au/medical-info/consumer-info/medicines-and-type-2-diabetes (accessed Aug 2018).
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