oral hypoglycemic agents

Drugs that are used to lower blood glucose levels are typically called "oral hypoglycemic agents." Other names you might come across are "anti-hyperglycemic agents" or (my least favourite) "anti-diabetic drugs." There are a rapidly increasing number of drug groups (and increasing numbers of drugs within each group) available to treat high blood sugar levels. Each group works through a different mechanism. That often allows multiple drugs to be used simultaneously as we take advantage of their different, but complimentary properties. There are drugs to:

slow down absorption of sugars from the gut:

Alpha-Glucosidase inhibitors (e.g. Glucobay [acarbose])

increase insulin production from the pancreas:

Sulfonylureas (e.g. Diabeta [glyburide])

Meglitinides (e.g. Gluconorm [repaglinide])

D-phenylalanine derivatives (e.g. Starlix [nateglinide])

decrease glucose release from the liver:

Biguanides (e.g.. Glucophage [metformin])

increase glucose uptake by fat & muscle cells:

Thiazolidinediones (TZDs or "glitazones"); (e.g. Actos [pioglitazone] or Avandia [rosiglitazone]).

do a whole bunch of these things (reduce appetite, increase insulin production from the pancreas, decrease glucose release from the liver) all at once:

GLP-1 Analogues; (e.g. Byetta [exenatide]) - this is not actually an oral hypoglycemic agent since it has to be given by injection, but it shares the same properties as many of these drugs so I'm taking the liberty of including it here. Besides, hey; this is my web site so I get to take these liberties!

DPP-4 Inhibitors; (e.g. Januvia [sitagliptin]).

Click the image above to see an illustration of the mechanism of action of oral hypoglycemic agents (OHA's).

So how do I decide which pill I'll prescribe? Well, in almost all cases the preferred oral hypoglycemic agent is metformin (especially if you are overweight). That's the easy choice and is based on its very long track record of safety and effectiveness, and the fact that metformin does not promote weight gain. What's harder is to know which drug to add next (assuming you need a second drug). These are some of the things that need to be considered when deciding:

	Glucobay is safe, but tends to cause unpleasant (though not serious) side-effects and isn't all that effective at reducing blood glucose levels.
	Glyburide is safe and effective, but tends to cause weight gain and can lead to hypoglycemia.
	Thiazolidinediones (Actos and Avandia) are effective, but tend to cause weight gain, can (in susceptible people) cause heart failure, increase the risk of certain types of fractures in women and, at least for Avandia, there is controversy about whether they increase the risk of heart disease (coronary artery disease).
	Byetta and Januvia are effective and don't cause weight gain (indeed, Byetta may even help you lose weight), but these are new drugs and thus we don't have a long track record of proven safety to rely on.

Lastly, it is to be noted that oral hypoglycemic agents are often used in combination with insulin in treating type 2 diabetes. This is done primarily in two circumstances:

If you have insulin resistance, the insulin you are giving yourself may not work particularly well. If you add a drug such as metformin or a TZD (Actos, Avandia), insulin resistance is reduced and the insulin often works more effectively; as a result your blood glucose control may well improve better than if you were on either insulin alone or oral hypoglycemic agents alone. Note that neither Actos nor Avandia are officially labelled in Canada as being "approved" for combined use with insulin (because this combination increases the risk of heart failure.

When oral hypoglycemic agents can keep the blood sugar levels down during most of the day, but are unable to keep the fasting (that is; before breakfast) values under control. This situation lends itself nicely to taking pills (particularly glyburide and metformin) during the day and insulin (NPH, glargine or detemir) at bedtime. The bedtime insulin keeps the fasting readings down and the pills keep the readings down the remainder of the day.