Publications
Partners
Type 2 diabetes is a serious condition that can lead to life-threatening complications if not well managed. Over 30% of all hospital admissions in Australia are diabetes related.
Medication available to lower blood glucose can be divided into two groups:
• Insulin, which can only be injected or delivered by glucose pump.
• All other anti-diabetic medication except insulin.
Drug-related treatment of type 2 diabetes can be approached in a step-by-step fashion:
Step 1
• Lifestyle modification + metformin (for obese patients, 1-3 doses per day), or
• Lifestyle modification + sulphonylureas (for non-obese patients).
If good blood glucose control isn’t achieved within 3 months (HbA1 > 7%), step 2 should follow.
Step 2 A
• Add a second drug from a different class. The second drug may be one of the following: metformin, sulphonylurea, basal insulin or pioglitazone (a thiazolidinedione).
NOTE: Although not a formal guideline, a more aggressive approach to blood glucose control is now becoming the norm. Newer medications such as DPP-4 inhibitors and incretin mimetics (see below) are now often used as the second drug of choice, while many experts advocate the use of insulin sooner rather than later.
Step 2 B
• If blood glucose levels are still not controlled within another 3 months, a third drug from a different class can be added.
Step 3
• If blood glucose levels are still not controlled within another 3 months, either start biphasic insulin or intensive insulin therapy.
Non-insulin medication options
An increasing array of medications are effective in lowering glucose levels in type 2 diabetics. They differ in their modes of action, side effects, cost and dosing schedule. The choice of the most suitable one needs to be made on an individual basis after a full medical assessment.
The main groups of oral blood glucose-lowering tablets are:
A. Biguanides
B. Sulphonylureas
C. Thiazolidinediones
D. Alpha-glucosidase inhibitors
E. Meglitinides
F. Incretin mimetics (GLP-1 agonists)
G. DPP-4-inhibitors
A. Biguanides (metformin)
Examples include Diabex, Diaformin, Formet, Genepharm metformin, Genrx metformin, Glucohexal, Glycomet, Glucophage, Metforbell and Metformin XR.
How it works: Metformin is currently the most well-known and most used anti-diabetic tablet. It’s one of the older anti-diabetic drugs, but still the first port of call. Biguanides help lower blood glucose by making sure the liver doesn’t produce too much glucose. Biguanides also lower the amount of insulin in the body. While biguanides act chiefly by decreasing the production of glucose in the liver, and increasing the transportation of glucose from the bloodstream into the cells, metformin functions only in the presence of some existing insulin. This medication will thus be of no use in patients where the pancreas has ceased to produce insulin.
When to prescribe: Metformin is most often the first glucose-lowering medication prescribed to an overweight or obese type 2 diabetic, and usually forms the first step in the treatment plan along with lifestyle modification. A low dosage (some days of the week) would be the first step, after which the dosage can slowly be increased (also to be taken seven days a week) over the first two months to lower the risk of side-effects. Patients may lose weight when starting metformin. This weight loss can indeed help control blood glucose. Metformin can also improve blood fat and cholesterol levels. This medication doesn’t generally cause hypoglycaemia, unless combined with other medications that increase insulin. It should not be prescribed to a diabetic with kidney problems.
Side effects: Metformin may cause nausea and vomiting if more than 2 - 4 alcoholic drinks a week are consumed while the patient is on the medication. Other side-effects include nausea, diarrhoea, headache, weakness, a metallic taste in the mouth and keto-acidosis. Keto-acidosis isn’t common in people with type 2 diabetes, and warrants urgent attention.
B. Sulphonylureas (gliclazide, glibenclamide, glipizide, glimepiride)
Examples include Diamicron, Genrx gliclazide, Glyade, Mellihexal, Nidem, Daonil, Glimel, Melizide, Amaryl, Aylide and Dimirel.
How it works: Sulfonylureas are one of the two most commonly prescribed medications for treating type 2 diabetes (the other is metformin). Sulfonylureas stimulate the pancreas to produce and secrete more insulin, thus lowering blood glucose levels. For these medications to work, the pancreas has to make some insulin.
When to prescribe: It’s most often prescribed in the second step of treatment, or as the first drug in non-obese type 2 diabetics. Glyburide shouldn’t be prescribed for the elderly and patients with compromised renal function, since it may cause hypoglycaemia. Glipizide or glimepiride is safe in the elderly and in those with kidney problems. Sulphonylureas may cause weight gain and should rather not be prescribed for overweight patients.
Side effects: Possible side effects include hypoglycaemia, diarrhoea, a skin rash or itching, and weight gain.
C. Thiazolidinediones (glitazones)
Examples include Avandia and Actos.
How it works: This class of drug helps overcome insulin resistance and may have some other beneficial effects on underlying metabolic defects. Thiazolidinediones help make the cells more sensitive to insulin. The insulin can then move glucose more efficiently from the blood into the cells for energy.
When to prescribe: As the second or third drug with metformin or sulphonylurea, or both.
Side effects: These may include weight gain, anaemia and fluid retention. More serious side effects include liver damage, chronic heart failure and fractures in women. It’s important to monitor patients’ liver function while taking thiazolidinediones. Although rosiglitazone is restricted due to an increased risk of heart damage, few people using this drug actually die of heart disease – this is possibly because blood glucose levels are better controlled.
D. Alpha-glucosidase inhibitors
An example is Glucobay (acarbose).
How it works: Alpha-glucosidase inhibitors act by delaying the absorption of carbohydrates from the intestine, resulting in a slower and lower rise in blood glucose throughout the day, especially straight after meals. This medication has a small but significant effect in lowering blood glucose and does not cause hypoglycaemia when used alone.
When to prescribe: Most often with sulphonylurea.
Side effects: They may cause flatulence, bloating, severe diarrhoea and nausea.
E. Meglitinides
An example is Novonorm (repaglinide), which is currently only available on private script.
How it works: Meglitinides act the same way as sulphonylureas (although they’re not chemically related) and shouldn’t be prescribed with this medication. They help the pancreas to produce and secrete more insulin straight after meals, lowering blood glucose levels. Meglitinide is fast acting.
When to prescribe: Meglitinide can be prescribed on its own or in conjunction with metformin.
Possible side effects: The meglitinides may cause hypoglycaemia and may affect liver function. Thus, liver tests should be performed regularly. Weight gain might also be an unwanted side-effect.
F. Incretin mimetics (GLP-1 agonists)
An example is Byetta (exenatide).
How it works: Byetta is an injectable drug that reduces glucose levels in the blood. Users inject themselves with regulated doses using a pen-like device twice daily before meals. Incretin mimetics mimic the effects of incretins (such as human-glucagon-like peptide-1, also called GLP-1), hormones produced by and released into the blood by the intestine every time the person eats. GLP-1 increases the secretion of insulin from the pancreas, slows absorption of glucose from the gut and reduces the action of glucagon, a hormone that increases glucose production by the liver. All three of these actions reduce levels of blood glucose. In addition, GLP-1 reduces appetite. Exenatide (Byetta) is a synthetic hormone that resembles and acts like GLP-1. In studies, exenatide-treated patients achieved lower blood glucose levels and experienced weight loss.
When to prescribe: This should only be prescribed with maximum doses of metformin or sulphonylurea, or in combination with both, where glycated haemoglobin (HbAlc) is over 7%.
Possible side effects: A common side effect is loss of appetite, nausea and vomiting, which typically diminishes with time. The drug is perhaps best known for the weight loss it causes.
G. DPP-4 inhibitors
Examples include Januvia (sitagliptin) and Galvus (vildagliptin).
How it works: DPP-4 (dipeptidyl-peptidase-4-inhibitor) enhances the body's own ability to control blood glucose levels and increases insulin when blood glucose is elevated, especially after eating. It heightens the GLP-1 effect (see explanation in snippet on incretin mimetics above).
When to prescribe: Most often as the first drug, or the second drug, to be added to the treatment regime. Note that these medications should not be prescribed to children, pregnant women, or breastfeeding women, and that doses should be lowered in patients with severe kidney disease.
Possible side effects: These include a runny or stuffy nose, sore throat, headache, nausea, stomach pain, or diarrhoea.
Medication available to lower blood glucose can be divided into two groups:
• Insulin, which can only be injected or delivered by glucose pump.
• All other anti-diabetic medication except insulin.
Drug-related treatment of type 2 diabetes can be approached in a step-by-step fashion:
Step 1
• Lifestyle modification + metformin (for obese patients, 1-3 doses per day), or
• Lifestyle modification + sulphonylureas (for non-obese patients).
If good blood glucose control isn’t achieved within 3 months (HbA1 > 7%), step 2 should follow.
Step 2 A
• Add a second drug from a different class. The second drug may be one of the following: metformin, sulphonylurea, basal insulin or pioglitazone (a thiazolidinedione).
NOTE: Although not a formal guideline, a more aggressive approach to blood glucose control is now becoming the norm. Newer medications such as DPP-4 inhibitors and incretin mimetics (see below) are now often used as the second drug of choice, while many experts advocate the use of insulin sooner rather than later.
Step 2 B
• If blood glucose levels are still not controlled within another 3 months, a third drug from a different class can be added.
Step 3
• If blood glucose levels are still not controlled within another 3 months, either start biphasic insulin or intensive insulin therapy.
Non-insulin medication options
An increasing array of medications are effective in lowering glucose levels in type 2 diabetics. They differ in their modes of action, side effects, cost and dosing schedule. The choice of the most suitable one needs to be made on an individual basis after a full medical assessment.
The main groups of oral blood glucose-lowering tablets are:
A. Biguanides
B. Sulphonylureas
C. Thiazolidinediones
D. Alpha-glucosidase inhibitors
E. Meglitinides
F. Incretin mimetics (GLP-1 agonists)
G. DPP-4-inhibitors
A. Biguanides (metformin)
Examples include Diabex, Diaformin, Formet, Genepharm metformin, Genrx metformin, Glucohexal, Glycomet, Glucophage, Metforbell and Metformin XR.
How it works: Metformin is currently the most well-known and most used anti-diabetic tablet. It’s one of the older anti-diabetic drugs, but still the first port of call. Biguanides help lower blood glucose by making sure the liver doesn’t produce too much glucose. Biguanides also lower the amount of insulin in the body. While biguanides act chiefly by decreasing the production of glucose in the liver, and increasing the transportation of glucose from the bloodstream into the cells, metformin functions only in the presence of some existing insulin. This medication will thus be of no use in patients where the pancreas has ceased to produce insulin.
When to prescribe: Metformin is most often the first glucose-lowering medication prescribed to an overweight or obese type 2 diabetic, and usually forms the first step in the treatment plan along with lifestyle modification. A low dosage (some days of the week) would be the first step, after which the dosage can slowly be increased (also to be taken seven days a week) over the first two months to lower the risk of side-effects. Patients may lose weight when starting metformin. This weight loss can indeed help control blood glucose. Metformin can also improve blood fat and cholesterol levels. This medication doesn’t generally cause hypoglycaemia, unless combined with other medications that increase insulin. It should not be prescribed to a diabetic with kidney problems.
Side effects: Metformin may cause nausea and vomiting if more than 2 - 4 alcoholic drinks a week are consumed while the patient is on the medication. Other side-effects include nausea, diarrhoea, headache, weakness, a metallic taste in the mouth and keto-acidosis. Keto-acidosis isn’t common in people with type 2 diabetes, and warrants urgent attention.
B. Sulphonylureas (gliclazide, glibenclamide, glipizide, glimepiride)
Examples include Diamicron, Genrx gliclazide, Glyade, Mellihexal, Nidem, Daonil, Glimel, Melizide, Amaryl, Aylide and Dimirel.
How it works: Sulfonylureas are one of the two most commonly prescribed medications for treating type 2 diabetes (the other is metformin). Sulfonylureas stimulate the pancreas to produce and secrete more insulin, thus lowering blood glucose levels. For these medications to work, the pancreas has to make some insulin.
When to prescribe: It’s most often prescribed in the second step of treatment, or as the first drug in non-obese type 2 diabetics. Glyburide shouldn’t be prescribed for the elderly and patients with compromised renal function, since it may cause hypoglycaemia. Glipizide or glimepiride is safe in the elderly and in those with kidney problems. Sulphonylureas may cause weight gain and should rather not be prescribed for overweight patients.
Side effects: Possible side effects include hypoglycaemia, diarrhoea, a skin rash or itching, and weight gain.
C. Thiazolidinediones (glitazones)
Examples include Avandia and Actos.
How it works: This class of drug helps overcome insulin resistance and may have some other beneficial effects on underlying metabolic defects. Thiazolidinediones help make the cells more sensitive to insulin. The insulin can then move glucose more efficiently from the blood into the cells for energy.
When to prescribe: As the second or third drug with metformin or sulphonylurea, or both.
Side effects: These may include weight gain, anaemia and fluid retention. More serious side effects include liver damage, chronic heart failure and fractures in women. It’s important to monitor patients’ liver function while taking thiazolidinediones. Although rosiglitazone is restricted due to an increased risk of heart damage, few people using this drug actually die of heart disease – this is possibly because blood glucose levels are better controlled.
D. Alpha-glucosidase inhibitors
An example is Glucobay (acarbose).
How it works: Alpha-glucosidase inhibitors act by delaying the absorption of carbohydrates from the intestine, resulting in a slower and lower rise in blood glucose throughout the day, especially straight after meals. This medication has a small but significant effect in lowering blood glucose and does not cause hypoglycaemia when used alone.
When to prescribe: Most often with sulphonylurea.
Side effects: They may cause flatulence, bloating, severe diarrhoea and nausea.
E. Meglitinides
An example is Novonorm (repaglinide), which is currently only available on private script.
How it works: Meglitinides act the same way as sulphonylureas (although they’re not chemically related) and shouldn’t be prescribed with this medication. They help the pancreas to produce and secrete more insulin straight after meals, lowering blood glucose levels. Meglitinide is fast acting.
When to prescribe: Meglitinide can be prescribed on its own or in conjunction with metformin.
Possible side effects: The meglitinides may cause hypoglycaemia and may affect liver function. Thus, liver tests should be performed regularly. Weight gain might also be an unwanted side-effect.
F. Incretin mimetics (GLP-1 agonists)
An example is Byetta (exenatide).
How it works: Byetta is an injectable drug that reduces glucose levels in the blood. Users inject themselves with regulated doses using a pen-like device twice daily before meals. Incretin mimetics mimic the effects of incretins (such as human-glucagon-like peptide-1, also called GLP-1), hormones produced by and released into the blood by the intestine every time the person eats. GLP-1 increases the secretion of insulin from the pancreas, slows absorption of glucose from the gut and reduces the action of glucagon, a hormone that increases glucose production by the liver. All three of these actions reduce levels of blood glucose. In addition, GLP-1 reduces appetite. Exenatide (Byetta) is a synthetic hormone that resembles and acts like GLP-1. In studies, exenatide-treated patients achieved lower blood glucose levels and experienced weight loss.
When to prescribe: This should only be prescribed with maximum doses of metformin or sulphonylurea, or in combination with both, where glycated haemoglobin (HbAlc) is over 7%.
Possible side effects: A common side effect is loss of appetite, nausea and vomiting, which typically diminishes with time. The drug is perhaps best known for the weight loss it causes.
G. DPP-4 inhibitors
Examples include Januvia (sitagliptin) and Galvus (vildagliptin).
How it works: DPP-4 (dipeptidyl-peptidase-4-inhibitor) enhances the body's own ability to control blood glucose levels and increases insulin when blood glucose is elevated, especially after eating. It heightens the GLP-1 effect (see explanation in snippet on incretin mimetics above).
When to prescribe: Most often as the first drug, or the second drug, to be added to the treatment regime. Note that these medications should not be prescribed to children, pregnant women, or breastfeeding women, and that doses should be lowered in patients with severe kidney disease.
Possible side effects: These include a runny or stuffy nose, sore throat, headache, nausea, stomach pain, or diarrhoea.
