Part 2. Combination drugs

We looked at the various classes of oral drugs and the choices in each class in part 1 of this article. In many cases, at least in the early stages of the disease, one pill in the sulfonylurea class or the biguanides class will work to manage the disease. As time progresses when it is evident that such a monotherapy is not sufficient, doctors either change to another class of oral drugs or add another oral drug such as a glitazone or starch breakdown inhibitor. There is no single “best” pill for treatment of Type 2 diabetes. One has to try more than one type of pill, combination of pills, or even pills supplemented by insulin. Taking more than one pill may help in many cases since each class of drugs acts in different ways to lower blood glucose levels. Metformin and a sulfonylurea can be taken together.

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When a combination of pills is recommended by doctors, the number of pills to be taken increases and there is the possibility that the patient forgets to take one of them. The drug industry has come up with an answer for such forgetfulness. In recent years, several drug companies have formulated two classes of drugs into a single pill. The advantages cited by the manufacturers for a single combination pill instead of two separate pills are (1) the convenience of taking a single pill for the patient and proper compliance and (2) economic benefit in that the combination pill may be cheaper than the two individual pills. But more than the cost benefit to the consumer, the drug manufacturers stand to benefit since the cost of production for the combination pill is reduced and only part of the savings is passed on to the consumer. In addition, the manufacturer files for a new patent for the combination pill which enables them to extend their marketing advantage. The combination pills that are currently marketed incorporate the older drugs such as sulfonylureas and metformin either together or with glitazones, and DPP-4 inhibitors.

Drugs with sulfonylurea: Glucovance combines glyburide with metformin and is marketed by Bristol-Myers Squibb since the year 2000. Metaglip is a combination of glipizide with metformin and has been marketed by Bristol-Myers Squibb since 2002. Avandaryl is marketed by Glaxo Smith Kline since 2005 and the ingredients are Avandia and glimepiride. Duetact is a mixture of Actos and glimepiride, marketed by Takeda since 2006. These pills are available with different doses of each component. In testing these pills for their efficacy the manufacturers compared them against the effect of one of the ingredients in the mixture and not against the additive effect of the two components taken separately. Naturally, the combinations showed better performance which enabled them to get FDA approval. The FDA requires bioequivalence of the effect of the combination drug with that of the two separate pills and not much more to get approval.

Drugs with metformin: While metformin has been combined with sulfonylureas as stated above, it has also been combined with glitazones, a DPP-4 inhibitor, and a meglitinides. Avandamet is a combination of Avandia and metformin sold by Glaxo Smith Kline since 2002. ACTOplus Met is marketed by Takeda since 2005 and is a mixture of Actos and metformin. Janumet is the latest on the scene having been approved in April 2007 by the FDA and marketed by Merck. Januvia, which was approved in October 2006, is a DPP-4 inhibitor that increases the level of incretin hormones produced in the intestines which enhance the synthesis and release of insulin from the beta cells of pancreas. In addition it decreases glucagon release from the alpha cells of the pancreas. Janumet adds the capability of metformin in suppressing glucose production by the liver to Januvia’s ability to enhance insulin secretion. Another drug combination of Prandin with metformin is in trials by Novo-Nordisk.

The advice to diabetic patients is to maintain the hemoglobin A1c level below 7 per cent in order to avoid long-term complications like diabetic neuropathy (nerve pain), diabetic nephropathy (kidney malfunction), eye diseases and cardiovascular complications such as heart attack and stroke. There are an estimated 21 million diabetics in the US alone (7 per cent of the total population) and more than 200 million diabetics worldwide. These numbers are expected to go up significantly as a function of lifestyle which calls for reduced physical activity and improper nutrition in addition to personal and workplace stress. As mentioned before, healthful diet and physical activity are essential to prevent the occurrence of Type 2 diabetes and when diabetes does occur oral medication has to be included in managing the disease. As with the single drugs diagnostic tests have to be performed to monitor liver function, and occurrence of lactic acidosis in patients who take the combination drug containing a glitazone or metformin.

We shall examine the circumstances when insulin will be needed for Type 2 diabetics and the choices available for different needs in another article.

Sethuraman Subramanian
subramaniansethu@hotmail.com

Disclaimer: This article is intended as an educational and information tool and is not a substitute for medical advice. Readers are encouraged to consult their personal physician before considering oral medication for diabetes treatment.

(Concluded)