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Part 1. Single drugs
Type 2 diabetes (formerly known as adult onset diabetes) arises from either an insufficient amount of insulin secretion by the pancreas and/or development of insulin resistance in which the cells are unable to get glucose that they need for their function. All Type 2 diabetics (90-95 per cent of all diabetic patients) may ultimately need adventitious (external injection) insulin but those who are in the early stages of the disease may get by with oral medications which will enable them to manage their diabetes. The one caveat that all diabetics should bear in mind is that medications are only the second line of defence in managing the disease and not a substitute for proper diet and exercise which primarily constitute the frontline defence for diabetes management.
When the body still produces insulin but insufficient to control the glucose levels in the bloodstream, there are several oral medications available to manage the disease. At the present time the pills that are available are members of six classes of drugs:
sulfonylureas, meglitinides, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, and the most recently approved
DPP-4 inhibitors. Let us look at each class and the available drugs along with the mode of action of these drugs.
Sulfonylureas: This class of drugs stimulates the beta cells of the pancreas to secrete more insulin.
Chloropropamide (brand name Diabinese) is the only first-generation drug in this class that is still in use. The second generation sulfonylureas are improvements on the molecular structure and are effective at smaller doses. The second generation drugs include
glipizide (brand names Glucotrol and Glucotrol XL made by Pfizer),
glyburides (Micronase, and Glynase made by Pfizer and
Diabeta made by Aventis), and glimepiride (brand name
Amaryl made by Aventis). These pills are taken one or two times a day, before meals. They all have very similar effects in controlling glucose levels but with varying side effects. One common feature in all of them is that they contribute to weight gain and can cause hypoglycemia (low blood sugar) in some cases. Some doctors avoid glyburide, at least for the elderly, who are susceptible to hypoglycemia (low blood sugar).
Meglitinides: Sulfonylureas and meglitinides are called insulinotropic agents. Meglitinides stimulate the pancreas to secrete more insulin. Like the sulfonylureas they should be taken before each meal.
Repaglinide (brand name Prandin made by Novo Nordisk),
Nateglinide (sold as Starlix by Novartis), and mitiglinide (sold by Takeda/Kissei as
Glufast in Japan) are the drugs on the market in this class. These drugs stimulate secretion of insulin faster and for a shorter period than
sulfonylureas.
Biguanides: Biguanides lower blood glucose levels mainly by diminishing the amount of glucose produced by the liver. The brand name drug,
Glucophage (made by Bristol-Myers Squibb) was sold in Europe long before it was approved in the US. The generic drug (Metformin) is now made by a variety of companies after the expiration of the patent in the US. Metformin is, by far, the most prescribed of all oral diabetes drugs. It is usually taken two times a day usually with food. One advantage of this drug is that it does not contribute to weight gain, unlike
sulfonylureas.
Thiazolidinediones: This group of drugs (also known as glitazones) enables the patient’s insulin to work better in the muscle and fat cells in addition to decreasing the production of glucose by the liver. These are taken at the prescribed dose once or twice a day with food.
Rosiglitazone (sold as Avandia by Glaxo Smith Kline), and
Pioglitazone (sold in the name of Actos by Lilly/Takeda) are the two drugs available in this class. Another drug
Troglitazone (sold by Warner-Lambert as Rezulin) was recalled by the company due to its tendency to cause liver problems. While the other two drugs are still on the market, it is advisable to check the liver function (through periodic diagnostic tests on blood) when taking these glitazones. Recently Avandia has been implicated in causing macular edema (a case of visual impairment) in a few patients on this medication.
Alpha-glucosidase inhibitors: This class of drugs prevents/mitigates the breakdown of starch (from foods such as rice, potatoes, bread, etc.) into glucose in the intestines by inhibiting the enzyme alpha-glucosidase thereby slowing down the rise of glucose in the blood soon after a meal. They should be taken with the first morsel of food. There are two drugs available in this class.
Acarbose (brand name - Precose sold by Bayer) and
Miglitol (sold as Glyset by Pfizer). These drugs have significant side-effects, the most prominent being flatulation and diarrhoea, and for this reason these are not widely prescribed or demanded.
Gliptins or DPP-4 inhibitors: This class of drugs is the latest to join the drug arsenal in the fight against diabetes. Gliptins inhibit an enzyme called dipeptidyl peptidase-4. The first drug to be marketed in this class is
Sitagliptin (marketed by Merck as Januvia) approved by US FDA in October 2006 as a once-daily drug. For a report on this drug visit
http://www.chennaionline.com/health/HealthManagement/2006/10article01.asp
This class of drugs is designed to raise the levels of a naturally occurring hormone in the stomach and intestine called GLP-1 normally released while eating. The drug inhibits the enzyme which breaks down this hormone with the concomitant production of insulin via stimulation by the hormone. The hormone also suppressed glucose production by the liver (by diminishing the production of glucagon by the alpha cells of pancreas). Other drugs that are under FDA approval or late stage clinical trials include
Vildagliptin (to be sold, when approved, as Galvus by Novartis),
Denagliptin by Glaxo Smith Kline and Saxagliptin being developed by Bristol-Myers Squibb.
Except for Metformin and sulfonylureas (except Amaryl) many of these drugs still have patent protection and hence the drugs are expensive. Where generic drugs are available it is recommended that those are used since they are much less expensive than the brand name drugs and have been proven equal to the brand name drugs in safety and efficacy.
Note: The brand name drugs mentioned here are the names used in the US. The drug makers may market the same in different countries under different names. In addition, in some countries like India, local drug manufacturers sell the branded drugs under different names manufacturing them by a different process than the one used by the original maker. This is possible because India, among other countries, did not recognise product patents until 2005. If a patented drug could be made by a different process then it was considered not to violate the original product patent. That has changed since 2005 when India signed the World Trade Organization (WTO) pact which now recognises the product patents too. However, if some drugs were made and registered with the drug regulatory agency in India prior to 2005 they could continue to be made and sold.
Although so many pills are available for diabetes treatment they may not all work well for every patient even if they are initially effective in bringing glucose levels down. The pills may not work at all if one had diabetes for more than 10 years and/or if one is on insulin therapy. Let us look at how best to augment the treatment in part 2 of this article.
Sethuraman Subramanian
subramaniansethu@hotmail.com
Disclaimer: This article is intended as an educational and informational tool and is not a substitute for medical advice. Readers are advised to consult their personal physician before considering their choice of oral medication for diabetes treatment.
(To be Concluded)
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