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Oral Hypoglycaemic Agents: Understanding Diabetes Medications for Type 2 Diabetes
Often dietary changes and exercise are not enough to bring elevated blood glucose levels (BGL) down to satisfactory levels in Type 2 Diabetics. In such cases people will need to begin taking an Oral Hypoglycaemic Agent, or OHA.
OHA’s are not a substitute to lifestyle changes, but they should be introduced in those who have made a genuine attempt to eat well and exercise but still have high HbA1c levels. They should also be introduced to people who have extremely high BGL’s and diabetic symptoms at diagnosis.
HbA1c is a measure of blood sugar control over several months. It can give a good estimate of how well you have managed your diabetes over the last 2 or 3 months. The test measures the amount of glycated haemoglobin in the blood. You will have more glycated haemoglobin if you have had frequent high levels of glucose in your blood. The higher your HbA1c, the higher the risk that you will develop diabetes related complications.
Each class of OHA’s works in different ways. Since Type 2 Diabetes is a progressive disease of increasing insulin resistance and decreasing beta cells, a person’s medication must be assessed regularly. BGL’s and HbA1c must be assessed if considering adjusting the current OHA dosage, adding another OHA or changing to a completely different OHA.
There are 6 main classes of Oral Hypoglycaemic Agents (OHA’s):
1) Biguanides
These OHA’s are called insulin sensitizers. They work to reduce insulin resistance in the cells, so allowing the insulin to work better in the body. They will reduce a persons fasting blood glucose level. They are usually the first choice of OHA offered to an overweight Type 2 Diabetic. The most common Biguanide is Metformin.
a) Metformin
Metformin has the following actions:
• Decreases the glucose absorbed in the gut
• Decreases the amount of glucose released from the liver
• Increases the uptake of glucose into the muscle and fat cells
• Increases the effect of insulin in cells
Metformin will not cause hypoglycaemia, as it does not increase the release of insulin. It does not stimulate appetite, so should not cause weight gain. However, side effects can include nausea and diarrhea but this can be decreased if taken with or immediately after food, and the dose is increased slowly from the start. They can cause stomach discomfort, which is important to note as these symptoms can be mistaken for other gastrointestinal issues.
Metformin should be ceased if a patient becomes pregnant and during major surgery. It should not be prescribed to someone with chronic renal failure.
Common brand names for Metformin include Diaformin 500mg, Diabex 500mg and Glucophage 500mg.
2) Sulphonylureas
These OHA’s are called insulin secretagogues. They work to increase insulin release from the pancreas. Sulphonylureas have the following actions:
• Increase the release of insulin from the pancreatic beta cells
• Increase the effect of insulin on the cells
• Make the liver more sensitive to insulin
Sulphonylureas are the only OHA that can cause hypoglycaemia, however this can be corrected by decreasing the dose. They also have a tendency to increase appetite and can cause weight gain. They can cause nausea and vomiting.
Sulpholyureas should not be taken during pregnancy. They are mostly metabolized in the liver, so should not be taken by those with liver disease. They may also decrease the affect of Warfarin.
Sulphonylureas have a similar makeup to sulphur medications, so should not be taken by those with a known allergy to these. They should be taken at meal times.
Common brand names of Sulphonylureas are Diamicron 30mg, Gliclazide 80mg Glimepiride- 1,2,3 and 4mg.
3) Thiazolidinediones (TZD’s or Glitazones)
These OHA’s are called insulin sensitizers. They work like Metformin, but they act mostly on the muscle cells. They decrease the fasting blood sugar and blood insulin after meals. TZD’s have the following action:
• Increase the uptake of glucose into the muscle cells
• Increase glucose uptake in the fat and liver cells.
TZD’s may take several weeks or months to take affect. The most common side effect is fluid retention. Weight gain may also be an issue. They should not be taken during pregnancy or whilst breastfeeding. They are also not recommended for those with liver disease.
The two TZD’s used in Australia are Rosiglitazone (Avandia) 4 or 8mg and Pioglitazone (Actos) 15, 30 or 45mg.
4) Alpha-Glucosidase Inhibitors
These OHA’s inhibit the enzyme alpha-glucosidase., which is involved in the breakdown of carbohydrate. They slow down the uptake of glucose and can reduce both fasting BGL and random BG.
Considering they are slowing down carbohydrate absorption, they can lead to symptoms such as bloating, flatulence and diarrhoea. This can be corrected by taking the medication with meals, and starting from a low dose and increasing slowly. They are not recommended for those with gastrointestinal disorders such as gastroparesis, Coeliac disease or irritable bowel syndrome.
5) Glitinides
These OHA’s increase insulin secretion at meal times. They should only be taken with meals, and are usually taken 2-3 times a day. There is a low risk of hypoglycaemia. They are not listed on the PBS, so are not generally used in Australia.
6) Combination OHA’s
OHA’s exert different effects and therefore can be taken in combination with each other. This is common practice and is usually a step by step process. A possible progression is outlined below. Your doctor will give you specific instructions but in general, the following steps are followed.
Step 1 – If a person's BGL is above 15mmol/L they are usually commenced on a Metformin. The initial dose will be increased until the BGL’s are less than 8mmol/L.
Step 2 – If the BGL remain above 8mmol/L a sulphonylurea, such as Diamicron, may be added. The initial dose can be increased every 1-2 weeks until the BGL are less than 8mmol/L. A pre-combined Metformin and Sulphonylurea is available called Glucovance. This may be used, but combined tablets make it more difficult to adjust dosages to reach desired BGL.
Step 3 – If the BGL remain above 8mmol/L a TZD may be added, and this is called triple therapy. The effect may take several months.
Step 4 – If BGL are still above 8mmol/L, insulin may be required.
Added to site on : Sunday, 21 March 2010