Which Oral Meds for Type 2 Diabetes?

Summarized by Robert W. Griffith, MD
August 14, 2007

Summary

Most oral antidiabetic drugs lower HbA1c to a similar extent. Metformin is the only one that also decreases LDL cholesterol and is one of the only ones that doesn't increase body weight; it has the best profile of benefit to risk. Metformin and sulfonylureas offer three advantages over newer agents: lower cost, longer use in practice, and more intensive scrutiny in long-term trials.

Introduction

An estimated 21 million people in the U.S. have diabetes, about 7% of the population. That's up from 2.5% in 1980. Despite the increase of the disease among the young, older people are still the largest age group affected: one in five aged 60 or over has diabetes. About 1.5 million people are newly diagnosed every year.

Lifestyle modifications have become a mainstay of treatment for people with full-blown diabetes. Studies consistently show that lifestyle changes alone - and particularly losing weight - can prevent the complications of diabetes. For some people, they eliminate or reduce the need for drugs. However, there's still need for effective anti-diabetic medications.

Oral medications

Oral diabetes medicines - pills you take by mouth - are thus just one treatment among several that doctors use to help people with diabetes. There are 6 categories of pills. These work in different ways. But they all: (a) lower blood sugar levels; (b) help improve the body's use of glucose; (c) decrease the symptoms of high blood sugar; (d) help keep people with diabetes functioning normally; and (e) may help prevent the complications, organ-damaging effects, and premature death that diabetes can cause.

• The sulfonylureas and meglitinides increase the secretion of insulin by the pancreas. The meglitidines are short-acting.
• Metformin (a biguanide) inhibits glucose production by the liver and decreases insulin resistance.
• The alpha-glucosidase inhibitors delay the absorption of glucose by the intestine.
• The thiazolidinediones decrease insulin resistance.
• The incretin mimetics block an enzyme, dipeptidyl peptidase 4, which results in improved insulin release and blood sugar control.

Since the drugs work in different ways, they are sometimes used in combination to enhance the effectiveness of treatment. Indeed, 25% to 50% of people with diabetes who start taking a drug will need to add another type of drug (or insulin) within six years.

Which medications are best?

An in-depth analysis of the scientific evidence on oral diabetes drugs has been conducted by researchers at Johns Hopkins University. The analysis, which was sponsored by the Federal Agency for Healthcare Research and Quality, screened the findings of over 216 published studies; it's published online by the journal Annals of Internal Medicine. The report does not cover the incretin mimetics, which are too new to have adequate data for comparative analysis.

The main findings

Newer drugs are no better. The thiazolidinediones, meglitinides, alpha-glucosidase inhibitors, and dipeptidyl peptidase 4 inhibitors (all more recently developed) are no more effective than the sulfonylureas and metformin, which have been around for decades. In fact, three of the newer medicines - acarbose, miglitol, and nateglinide decrease HbA1c less than the other drugs. One older type of medicine, the sulfonylureas, and an older drug named metformin work just as well as those in the four newer classes. Indeed, several of the newer drugs are less effective than the older ones.
Newer drugs are no safer. All diabetes pills have the potential to cause adverse effects, both minor and serious. The drugs' side effect profiles may be the most important factor in your choice.
Metformin emerges as a superior diabetes drug based on the available evidence. This medicine lowers HbA1c the same amount or more than other drugs, does not cause weight gain, decreases low-density lipoprotein (LDL) and triglycerides, and appears to have the safest profile when comparing serious side effects in people who do not have kidney, liver, or heart disease.
Taking two diabetes drugs can improve blood sugar control. Many people with diabetes do not get enough help from one drug - two may be necessary. However, taking two drugs can raise the risk of adverse effects and increase costs. Recommended combinations are metformin with either glipizide or glimepiride.

Questions of cost

Newer drugs are more expensive. The newer diabetes medicines cost many times more than the older ones. Metformin, glipizide, and glimeripide are available as low-cost generics ($10 to $60). Should these drugs cause problems, Actos^® (pioglitizone) may be an option to consider. Actos and Avandia^® (rosiglitizone) have been heavily promoted to doctors and consumers, however, and have been over-prescribed. A new review of rosiglitazone (Avandia) has found no evidence of any benefits of the drug over other diabetes medications and, because of side effects such as edema, fractures, and possible increased risk of MI, the review advises a "very cautious approach to rosiglitazone use" and recommends that if possible, other antidiabetic medications should be employed.

Sources of information

This brief summary is an amalgam of the main points from the Johns Hopkins review in the Annals of Internal Medicine and a publication from Consumer Reports: Best Buy Drugs. These can be found online at: http://www.annals.org/cgi/contnet/full/0000605-200709180-00178v1 and http://www.crbestbuydrugs.org/PDFs/type2diabetes.pdf
The review of rosiglitazone is summarized at: http://www.medscape.com/viewarticle/559972?sssdmh=dm1.287257&src=nldne

Source

• Systemic review: Comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. S. Bolen , L. Feldman, J. Vassey,  et al., Ann Intern Med, 2007

Related Links
An Consumer Reports' Best Buy Drugs: The Oral Diabetes Drugs
Postponing the Addition of Insulin
Statins in Diabetes

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