Tablets for Type 2’s

When “Diet and Exercise” fails

Treatment protocols

The classic approach to Type 2 diabetes therapy usually begins with a diet and exercise programme. If, or when, this fails and fasting blood glucose levels or HbA1c levels remain high then the next step is generally oral medication – tablets, in other words. It is usually assumed that the patient has understood, and adhered to, the advice or guidelines given at the time of diagnosis. Yet in many cases, it seems, the appropriate knowledge and understanding is lacking; the importance of patient education at this early stage should never be undermined.

The choice of agent(s) will depend on your blood glucose levels and on your weight status. The blood glucose lowering tablets are NOT forms of insulin, nor can they replace insulin. They aim to help you make the most of the insulin that is available. The success of oral therapy is totally dependent on the ability of the beta cells to produce some insulin. If your beta cells cannot produce sufficient insulin, then there are no two ways about it – you will need to start taking insulin injections.

Combination Therapy

With the recent introduction of several new types of tablet medication, there is now potential for ‘combination therapy’ – a mixture of agents tailored to the needs of the individual (and this may include insulin).

Choice of Hypoglycaemic Agents

Class Drug Name Proprietary Name(s) Subsided? Access
First Generation Chlorpropamide*

Tolbutamide Diatol Yes 3-months’ supply dispensed at one time.
Second generation Glibenclamide Gliben



Yes 3-months’ supply dispensed at one time.
Gliclazide Apo-Gliclazide


Yes 3-months’ supply dispensed at one time.
Glipizide Minidiab


Yes 3-months’ supply dispensed at one time.

Third generation Glimeprimide*



Metformin Metomin


Yes 3-months’ supply dispensed at one time.
PPARg Agonists (Glitazones):
Pioglitazone Actos Yes Special Authority required;
3-months’ supply dispensed at one time.
Rosiglitazone Avandia No GP prescription required, then item can be purchased from a pharmacy or through Diabetes Supplies
a-Glucosidase Inhibitors:
Acarbose Glucobay Yes Special Authority required;
3-months’ supply dispensed at one time.

*Not currently available in New Zealand

Important Note

Rosiglitazone was withdrawn from the New Zealand market on 29 April 2011 after a safety review found an elevated risk of cardiovascular events in patients treated with this medicine.

>> Article by Ministry of Health



A few words about the different drugs and their names…

Each drug belongs to a particular class; this is a group of drugs with similar activity and usually the chemical compounds are closely related. Each drug has an individual chemical name, a name that the developer of the drug gives to it. Each drug also has a brand name, a name that the company manufacturing the drug effectively gives to it.

In addition, you may hear reference to ‘second’ or ‘third generation’ drugs – these are effectively sub-classes that have evolved over a period of years.

Take, for example, Glipizide. This is a second generation sulphonylurea. In the UK, Glipizide is marketed by the company Pfizer Ltd as GlibineseTM. Glipizide is also marketed by the company Pharmacia & Upjohn as MinodiabTM.


The blood glucose lowering ability of sulphonylureas was discovered by accident in the 1940s. They were the only type of oral hypoglycaemic agent available for people with Type 2 diabetes up until the mid 1990s.

Mechanism of action

The sulphonylureas stimulate the release of insulin from beta cells. They ‘sentitize’ beta cells to glucose, so that effectively more insulin is secreted at all blood glucose levels.


The likelihood of success with sulphonylurea treatment is influenced by a number of factors, including the following:

  • duration of diabetes < 5 yrs
  • fasting blood glucose < 11.1 mmol/l
  • body weight 110 – 160 % ideal body weight
  • little or no previous insulin therapy

There are a wide range of sulphonylureas available with different durations of action.

Side Effects

The most important side effects of the sulphonylureas are hypoglycaemia and weight gain. The potential to cause hypoglycaemia depends on the particular sulphonylurea – some appear to cause hypoglycaemia more frequently than others (especially chlorpropamide and glibenclamide).


Hypoglycaemia induced by excess sulphonylurea may persist until the drug has been cleared from the body; this is because it will continue to stimulate insulin secretion in spite of the low blood glucose level. Note, also, that glucagon injection is generally unsuitable for treatment of sulphonylurea-induced hypoglycaemia – this is because glucagon also stimulates insulin production (this is irrelevant, of course, in Type 1 patients who have no beta cell function).

All work best if taken approximately 20 minutes before a meal, although gliclazide works fine if taken with or just before a meal.

Meglitinides (Note: not currentlly available in NZ)

The meglitinides are a new class of drugs which, like the sulphonylureas, stimulate insulin secretion. Unlike the sulphonylureas, however, they act quickly. Repaglinide has a peak effect occurring within an hour of taking the tablet; the shortest acting of the sulphonylureas have a duration of 2 – 4 hours.

The role of repaglinide in diabetes therapy has not yet been truly defined. Taken three times daily with meals, however, its potential clearly lies with its ability to combat postprandial hyperglycaemia i.e. the high blood glucose levels that often follow a high carbohydrate meal.


The biguanides phenformin and metformin have been around since the 1950s. Phenformin, however, was withdrawn from use in the UK on account of its potential to induce lactic acidosis, a lethal side effect.

Mechanism of action

The biguanides have several metabolic effects and their modes of action are far from having been elucidated. Metformin increases insulin sensitivity; by increasing insulin action it increases glucose utilization.

Metformin also decreases ‘hepatic glucose production’ (HGP), which is glucose released into the bloodstream by the liver. (The liver normally tops up the blood glucose during fasting and especially overnight. Insulin resistance at the liver can result in an increased output of glucose.)

In addition to its blood glucose lowering effects, metformin also has beneficial effects on blood lipid profiles.


Metformin can be used on its own, or in conjunction with sulphonylurea therapy. It has particular advantages in the treatment of obese people with type 2 diabetes.

Metformin should be avoided if kidney function is impaired – the drug is usually excreted by the kidneys; if its clearance is reduced then it may accumulate to dangerous levels.

Side Effects

The main side effects of metformin are gastrointestinal – abdominal discomfort, nausea or diarrhoea. These can be minimised by taking the tablets at the end of a meal and by increasing the dose very slowly.

Less common side effects include a metallic taste in the mouth and reduced absorption of vitamin B12 and folate (usually occurs over a prolonged period).

Lactic acidosis is a rare complication of metformin therapy. It is more likely in patients with impaired liver function or those with a history of binge drinking or alcoholism.


The effects of metformin are not instantaneous. It may be up to two weeks before a significant improvement in blood glucose levels can be seen.

Acarbose can reduce the effectiveness of metformin therapy.


PPARg Agonsists

These new drugs are commonly referred to as the glitazones or sometimes as the thiazolidinediones (TZDs). They decrease insulin resistance by enhancing the effects of insulin. Like biguanides, they sensitize the body’s tissues to insulin, but their mode of action is different.

Troglitazone (RezulinTM) was the first TZD to hit the market. This was withdrawn, however, because of its apparent ability to cause potentially fatal liver damage.

In recent years, concerns over Avandia (Rosigltitazone) have arisen, concerning potential association with fatal heart-related incidents ( See NOTE above ).


a-Glucosidase Inhibitors

People with Type 2 diabetes are often prone to high blood glucose levels after meals – postprandial hyperglycaemia – and it is the starch content of the meal that is largely responsible for this rise. Starch or ‘complex carbohydrates’ are made up of long strings of simple sugars; they are polysaccharides. When they are digested they are broken down by enzymes into smaller chains – oligosaccharides – and then, eventually, into single sugar molecules (mostly glucose) – monosaccharides. Only monosaccharides can be absorbed through the lining of the gut into the bloodstream. The enzymes that break down oligosaccharides are collectively called

The a-glucosidase enzymes have special binding sites where the oligosaccharides sit tightly whilst the bonds holding the sugar molecules together are broken. a-glucosidase inhibitors are very similar in their structure to oligosaccharides and can fit neatly into the binding sites, blocking out the molecules that should be being digested (this is why they are known as ‘competitive inhibitors’ of the digestive enzymes). When the inhibitor moves out of the docking site on the digestive enzyme, the carbohydrate may have been moved further along the small intestine. Acarbose, therefore, delays the digestion of starchy foods and slows down the rise in blood glucose that would usually occur during the 30 – 120 mins after a meal.


Acarbose is used to help blood glucose control in response to meals. Because it effectively draws out the digestion process, it can also help prevent hypoglycaemia later on. A significant improvement in blood glucose levels will only be seen in those people who would normally eat a high carbohydrate diet. Acarbose may be used on its own, or in conjunction with sulphonylurea therapy.

Side Effects

Gastrointestinal disturbances, particularly flatulence, may result from undigested carbohydrate passing through the gut. The severity of such side effects can be reduced by starting on a low dose and increasing the dose slowly.


Because of the way acarbose works, it must be present at the site of the enzymatic digestion at the same time as the carbohydrate. Therefore tablets must be taken with the first bite of a meal.

If acarbose is being used in conjunction with sulphonylurea or insulin therapy then the patient should be aware that hypoglycaemia must be treated with glucose. Any other carbohydrates, including sucrose (table sugar) will not be rapidly absorbed in the presence of acarbose.