Oral treatments to control blood sugar


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When are oral medicines used?

In type 1 diabetes (insulin-dependent diabetes), the cells in the pancreas that produce insulin are progressively destroyed by an immune reaction, stopping the production of insulin.

Insulin replacement treatment is therefore needed for life, because we cannot make the beta cells in the pancreas work again to produce insulin.

Insulin can't be taken in tablet form, because it is broken down in the digestive system. This destroys its effect. Insulin is given by injection.

Type 2 diabetes

Type 2 diabetes (non-insulin dependent diabetes) is different because the pancreas still produces insulin. Instead, problems are caused because:

  • insulin is produced inefficiently in response to surges of blood sugar, eg following a meal
  • the insulin produced gets less effective at controlling blood sugar, because the cells in the body become increasingly resistant to it. This is called 'insulin resistance'.

    Treatment for type 2 diabetes involves either improving insulin release in response to meals, or reducing the resistance of the body cells to the effect of insulin.

    Diet and exercise are the first treatments used to improve insulin resistance in type 2 diabetes.

    If blood sugar is not adequately controlled after at least three months of healthy eating and increasing exercise, oral medicines are used.

    What oral medicines are used in type 2 diabetes?

    There are various types of oral medicine that can be used to control blood sugar in type 2 diabetes.

      How do they work?

      Oral medicines work in five basic ways to lower blood glucose in Type 2 diabetes.

      1. Reducing insulin resistance: metformin and glitazones

      Metformin works mainly by reducing the amount of glucose produced by cells in the liver, and by increasing the sensitivity of muscle cells to insulin.


      Metformin also reduces the amount of sugar produced by cells in the liver and reduces the absorption of glucose from the gut after eating.

      Term watch

      Beta cells: cells in the pancreas that produce insulin.

      Pioglitazone works by increasing the sensitivity of liver, fat and muscle cells to insulin. This medicine may also preserve the function of the beta cells in the pancreas.

      Pioglitazone also reduces the amount of glucose produced by the liver.

      2. Stimulating insulin release: sulfonylureas and meglitinides

      The sulfonylureas and meglitinides work mainly by stimulating the beta cells in the pancreas to release more insulin.

      Meglitinides start to work more quickly and have a shorter effect than the sulfonylureas. They are taken to enhance insulin production during meals.

      3. Slowing the absorption of sugar from the gut: acarbose

      Carbohydrates that we eat need to be broken down into simple sugar molecules in the gut before they can be absorbed.

      This is done by an enzyme called alpha-glucosidase that is found in the lining of the gut.

      Acarbose works by blocking the action of this enzyme.

      This delays the absorption of sugar molecules from the gut, so that high peaks of blood glucose after eating are avoided.

      4. DPP-4 inhibition: gliptins

      Hormones from the small bowel, known as incretins, normally stimulate insulin release from the pancreas after meals.

      These hormones include one called glucagon-like peptide-1 (GLP-1), which is broken down by an enzyme called dipeptidyl peptidase-4 (DPP-4).

      DPP-4 inhibitors, called gliptins (eg linagliptin, sitagliptin, saxagliptin and vildagliptin) prevent the breakdown of GLP-1, which allows more insulin to be produced after meals. This reduces post-prandial hyperglycaemia (increased blood glucose levels after meals).

      The gliptins also suppress the release of another hormone from the pancreas called glucagon, which works against insulin. This further action of these new drugs improves glucose control.

      5. Increasing excretion of glucose in urine: gliflozins

      Gliflozins are a relatively new class of medicines that lower blood sugar by increasing its excretion in the urine.

      Gliflozins works in the kidneys.

      Normally, when the kidneys filter and clean the blood, glucose is filtered out of the blood at the same time.

      The glucose is then reabsorbed back into the blood by a mechanism called the sodium-glucose co-transporter 2 (SGLT2).

      The kidneys normally reabsorb glucose back into the blood even when the levels of glucose in the blood are too high, as in diabetes.

      Gliflozins works by inhibiting the SGLT2 transporter. This allows excess glucose to be filtered out of the blood and excreted in the urine.

      Which is most suitable for me?

      The medicine your doctor prescribes for you will depend on various characteristics such as your age, body weight and kidney and liver function.

      Since it does not cause weight gain, metformin is usually the first choice of medicine for overweight people with type 2 diabetes whose blood sugar is not controlled by diet alone.

      A sulfonylurea is the first choice for people who are not overweight or who cannot take metformin.

      Gliclazide is the most commonly used.

      Sulfonylureas have the potential to cause low blood sugar levels (hypoglycaemia) and so may not be appropriate for certain people where this could be a problem, for example people living alone, or people with occupations where low blood sugar could be dangerous.

      Glibenclamide is longer-acting than other medicines in this group, which makes it more likely to cause hypoglycaemia. For this reason, it isn't recommended for elderly people.

      If blood sugar is not controlled sufficiently with either of these first choices, the next step would be to add a sulfonylurea to treatment with metformin, and vice versa.

      If these combinations fail or are not appropriate, one of the newer medicines can be tried.

      Newer medicines

      The meglitinides are an alternative to sulfonylureas for people who have erratic lifestyles or irregular meal times and hence a higher risk of low blood sugar (for example due to a busy work schedule, shift work, or fasting for religious or cultural reasons):

      • nateglinide is only licensed for use in combination with metformin
      • repaglinide can be used either with metformin or on its own.

        Pioglitazone can be added to treatment with either metformin or a sulfonylurea or both. The combination product can reduce the number of tablets that people on these combinations need to take.

        The gliptins are another option and are licensed to be used with metformin, a sulfonylurea or a glitazone. These are also available in combination products with metformin.

        Dapagliflozin is a further option that can be added to treatment with metformin or a sulphonylurea. It is not recommended in combination with pioglitazone.

        When are oral treatments not suitable?

        If your blood sugar is not adequately controlled using a combination of these medicines, you may eventually need insulin treatment.

        This can either be added to the oral medicines, or may replace them entirely.

        During pregnancy, oral medicines were not previously recommended and are usually replaced by insulin, but the recent NICE guidelines in 2008 endorse metformin for use in pregnancy, either alone or with insulin.

        There are now three new injectable medicines that are an alternative to insulin injections for people whose blood sugar is poorly controlled on metformin, a sulphonylurea, a glitazone, or a combination of these.

        They are exenatide (Byetta and Bydureon), liraglutide (Victoza) and lixisenatide (Lyxumia).

        Insulin treatment tends to increase weight whereas these medicines cause weight loss, which is an advantage for people with type 2 diabetes not controlled by oral medicines who are overweight.

        Exenatide, liraglutide and lixisenatide are incretin mimetics, which have a structure similar to GLP-1 that is found in the bowel. They are not broken down by the DPP-4 enzyme system.

        These medicines increase insulin secretion, especially after meals, and reduce glucagon secretion, which restricts the liver from releasing glucose. They also reduce appetite and slow down the stomach emptying food by up to an hour after eating, which prevents a rise in blood glucose levels after eating.

        Liraglutide and lixisenatide are given by injection under the skin (subcutaneous injection) once daily.

        Exenatide is given by injection under the skin either twice daily, up to an hour before main meals (Byetta) or once a week (Bydureon).

        How are oral medicines taken?

        All the oral medicines for type 2 diabetes are tablets that are taken by mouth.

        • Metformin is taken two or three times a day, with or after meals.
        • Pioglitazone is usually taken once a day, with or without food.
        • Sulfonylureas are usually taken once or twice a day with breakfast, though this depends on the individual medicine and dosage.
        • Nateglinide and repaglinide are taken about 15 to 30 minutes before each main meal.
        • Acarbose tablets should be chewed with the first mouthful of food, or swallowed whole with a little liquid immediately before a meal.
        • Linagliptin, sitagliptin and saxagliptin are taken once daily, vildagliptin once or twice daily. They can all be taken either with or without food.
        • Dapagliflozin and canagliflozin are taken once a day, either with or without food.

          What are the side-effects?

          All medicines have side-effects, but it doesn't mean everyone will experience them. People respond to medicines in different ways.

          Oral medicines for type 2 diabetes have few side effects when taken properly.


          The most common side effects of metformin are digestive in nature – feeling or being sick, diarrhoea, abdominal pain, loss of appetite and a metallic taste.

          Side-effects usually improve quickly and can be minimised if the dose is increased gradually. There is a slow-release preparation of metformin available which may reduce gastrointestinal side-effects.


          Sulfonylureas can encourage weight gain, and because they stimulate insulin release they can cause hypoglycaemia (low blood glucose).

          Sulphonylureas can also cause mild digestive side effects such as feeling or being sick, constipation or diarrhoea.

          On rare occasions they may cause allergic reactions, or problems with the liver or blood.


          The most common side effects of pioglitazone are weight gain and fluid retention that can cause swelling of the legs (oedema). Fluid retention can sometimes cause or worsen heart failure.

          There is an increased risk of bone fractures with this medicine, particularly in women, and on rare occasions it may cause liver problems.


          Side-effects of repaglinide and nateglinide are few, but include hypoglycaemia, digestive side effects and allergic reactions.


          The main side effect associated with acarbose is flatulence, though this tends to decrease with time.

          It's caused by an increase in gas due to the fermentation of undigested carbohydrate in the bowel.

          It can also cause hypoglycaemia. If it does, you should take glucose not sucrose – acarbose delays the effect of sucrose.


          Linagliptin, sitagliptin, saxagliptin and vildagliptin cause less hypoglycaemia than sulfonylureas and do not cause weight gain. Their most common side-effects include digestive side effects and swollen ankles.

          Vildagliptin has rarely been associated with liver problems.

          This class of medicines has been rarely reported as causing acute pancreatitis, a serious inflammatory condition of the pancreas, and these medicines should therefore be stopped and medical advice sought if you experience persistant, severe abdominal pain.

          Exenatide, liraglutide and lixisenatide

          With exenatide the main side-effect is nausea and vomiting.

          These side-effects can be limited by starting with a small dose for four weeks and then building up to a maximum dose at about one month.

          With liraglutide and lixisenatide the most common side effects are also digestive in nature, such as nausea, vomiting, diarrhoea, constipation and indigestion.

          These medicines can also rarely cause acute pancreatitis, and should be stopped and medical advice sought if you experience persistant, severe abdominal pain.


          The main side-effects associated with gliflozins are an increased need to pass urine, and urinary tract or thrush infections due to the increase in sugar in the urine.

          What can I do to help myself?

          Oral medicines are not a substitute for healthy eating and more exercise – which you should continue to do while on treatment.

          Your diabetes health professional will advise you whether or not you need to monitor your blood sugar so you can see how effective a medicine is and make alterations to your diet and lifestyle if necessary.

          Checking a three monthly blood test called the 'glycated haemoglobin' or 'HbA1c' can give you an idea of your glucose control.

          The target for this blood tests varies between individuals according to your age and other medical problems, but very good diabetes control is defined as an HbA1c of 48 to 53 mmol/mol.

          Check with your doctor or pharmacist before taking other medicines in combination with tablets for diabetes – some medicines can affect the action of diabetes tablets, particularly the sulfonylureas.

          Other people also read:

          Diabetes: how common is diabetes?

          Blood glucose levels: how can I measure blood sugar levels?

          Type 1 diabetes (insulin-dependent diabetes) is caused by a lack of insulin output because of auto-immune damage to the pancreas gland.

          Type 2 diabetes (non-insulin dependent diabetes) is strongly associated with being overweight, but it's less clear what causes it, compared to the Type 1 disease.


          Holm P, Mant J, Diaz J, Turner C on behalf of the Guidelines Development Group. management of type 2 diabetes: summary of updated NICE Guidance. British Medical Journal 2008; 336: 1306-08.

          NICE Clinical Knowledge Summaries: Type 2 Diabetes

          Based on a text by Helen Marshall, pharmacist

          Last updated

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