Type 2 diabetes has a number of drug treatment options to be taken by mouth known as oral antihyperglycemic drugs or oral hypoglycemic drugs.
Oral diabetes drugs are usually reserved for use only after lifestyle measures have been unsuccessful in lowering glucose levels to the target of an HbA1c below 7.0%, achieved through an average glucose reading of around 8.3-8.9 mmol/L (around 150-160 mg/dL).
The lifestyle measures that are critical to type 2 diabetes management are diet and exercise, and these remain an important part of treatment when pills are added.
People with type 1 diabetes cannot use oral pills for treatment, and must instead take insulin.
How do oral drugs lower glucose levels?
Metformin is the most widely used oral antihyperglycemic drug and reduces the amount of glucose released by the liver into the bloodstream.
Oral antihyperglycemic drugs have three modes of action to reduce blood glucose levels:
- Secretagogues enhance insulin secretion by the pancreas
- Sensitizers increase the sensitivity of the peripheral tissues to insulin
- Inhibitors impair gastrointestinal absorption of glucose.
Each class of antihyperglycemic drug has a different adverse event or safety profile, and side effects are the main consideration when it comes to choosing a medication.
Possible side effects range from weight gain, through gastrointestinal ones such as diarrhea, to pancreatitis and more serious problems. Hypoglycemia is also a possible adverse event.
What oral drugs are available for type 2 diabetes?
No one particular choice of oral hypoglycemic is considered the most effective form of treatment – the decision over which drug to use is instead based on:
- Consideration of the adverse side effects
- Convenience and overall tolerability
- Personal preference.
In reality, weighing up each drug is something to do in partnership with a prescriber – guidelines partly drawn up by the American Diabetes Association list a great number of advantages and disadvantages for each of the available drug treatments, including the consideration of cost.
The use of a single drug can be escalated to combination therapy with a second drug in an effort to improve glycemic control.
Metformin is usually the first treatment offered, however, and it is the most widely used oral antihyperglycemic. Metformin is a sensitizer in the class known as biguanides; it works by reducing the amount of glucose released by the liver into the bloodstream and increasing cellular response to insulin. A metformin pill is usually taken twice a day.
This drug is a low-cost antihyperglycemic with mild side effects that can include diarrhea and abdominal cramping. Metformin is not associated with weight gain or hypoglycemia.
Sulphonylureas are secretagogues that increase pancreatic insulin secretion. There are several drug names in this class, including:
Again, the choice of drug is an individual one. In the case of sulphonylureas, the choice depends on daily dosing and the level of side effects. These drugs are associated with weight gain and hypoglycemia.
Glitazones (also known as thiazolidinediones) are sensitizers – they increase the effect of insulin in the muscle and fat and reduce glucose production by the liver.
Two glitazones are available: pioglitazone and rosiglitazone. These drugs can have the side effects of weight gain or swelling and are associated with increased risks of heart disease and stroke, bladder cancer and fractures.
In the UK, rosiglitazone was withdrawn from the market over concerns about adverse events. In 2015, it remains available in the US, with information on its safety provided by the US Food and Drug Administration (FDA).
Alpha-glucosidase inhibitors are intestinal enzyme inhibitors that block the breakdown of carbohydrates into glucose, reducing the amount absorbed in the gut.
Available as acarbose and miglitol, they are not usually tried as first-line drugs because of common side effects of flatulence, diarrhea and bloating, although these may reduce over time.
Dipeptidyl peptidase-4 (DPP4) inhibitors include alogliptin, linagliptin, saxagliptin and sitagliptin.
Also known as gliptins, DPP4 inhibitors have a number of effects, including stimulating pancreatic insulin (by preventing the breakdown of the hormone GLP-1). They may also help with weight loss through an effect on appetite.
These drugs do not increase the risk of hypoglycemia. Mild possible side effects are nausea and vomiting.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors include canagliflozin and dapagliflozin. They work by inhibiting the reabsorption of glucose in the kidneys, causing glucose to be excreted in the urine (glycosuria).
SGLT2s may also cause modest weight loss. Side effects include urinary infection.
Meglitinides include repaglinide and nateglinide. They stimulate the release of insulin by the pancreas. Meglitinides are associated with a higher chance of hypoglycemia and must be taken with meals three times a day. As a result, these drugs are less commonly used.
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