attributable to diabetes and 2) to calculate and compare the total and per capita medical expen- ditures for people with and without diabetes. …
Treating Type 2 Diabetes:
The Oral Diabetes Drugs
Comparing Effectiveness, Safety, and Price
Our Recommendations
Six types of oral medicines and 11 individual drugs are now available to help the 21 million people in the US with type 2 diabetes control their blood sugar when diet and lifestyle change are not enough Our evaluation of these medicines found the following: I Newer drugs are no better One older type of medicine, the sulfonylureas, and an older drug named metformin work just as well as four newer classes Indeed, several of the newer drugs are less effective than the older ones I 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 I Newer drugs are more expensive The newer diabetes medicines cost many times more than the older ones I Taking more than one diabetes drug can improve blood sugar control Many people with diabetes do not get enough help from one drug Two or more may be necessary However, taking more than one diabetes drug raises the risk of adverse effects and increases costs Taking effectiveness, safety, adverse effects,
dosing, and cost into consideration, we have chosen the following as Consumer Reports Best Buy Drugs if your doctor and you have decided that you need medicine to control your diabetes: I Metformin alone or with glipizide or glimepiride I Glipizide and Glipizide Sustained Release alone or with metformin I Glimepiride alone or with metformin These medicines are available as low-cost generics 10 to 60 If you have been diagnosed with diabetes, we recommend that you try metformin first unless your health status prevents it If metformin fails to bring your blood sugar into normal range, we recommend you add glipizide or glimepiride Should either of those drugs cause problems, Actos pioglitazone may be an option you and your doctor will want to consider Actos and Avandia rosiglitazone have been heavily promoted to doctors and consumers, however, and have been over-prescribed This report was released and last updated in July 2007
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Consumer Reports Best Buy Drugs
Treating Type 2 Diabetes: The Oral Diabetes Drugs
Welcome
This report compares the effectiveness, safety, and cost of medicines used to treat type 2 diabetes It is part of a Consumers Union and Consumer Reports project
to help you find safe, effective medicines that give you the most value for your health-care dollar To learn more about the project and other drugs weve evaluated for other diseases and conditions, go to wwwCRBestBuyDrugsorg Type 2 diabetes is one of the most serious medical conditions affecting our nation today The number of people who have it has been rising alarmingly in recent years That includes thousands of children and young adults Type 2 diabetes used to be referred to as adult onset diabetes No longer In recent years, the incidence among young people has exploded Much of that surge has been linked to the dramatic increase in the last 20 years in the number of young people who are overweight or obese and who are physically inactive The statistics are sobering An estimated 21 million people in the US have diabetes, about 7 percent of the population Thats up from 25 percent of the population in 1980 Despite the increase of the disease among the young, older people are still the largest age group affected: one in five people aged 60 or over has diabetes About 15 million people are newly diagnosed every year But despite widespread attention to the diabetes epidemic, about one
in three people who have diabetes some 7 million people have not been diagnosed and do not know they have it Timely diagnosis is no assurance either: a third of the people who have been diagnosed with diabetes fail to receive the medical care and medicines that research shows to be effective Why is diabetes of such concern? Studies conclusively show that diabetes more than doubles the risk of developing and dying of heart disease and other problems It is as potent a predictor and risk factor for heart disease and heart attack as cigarette smoking, high blood pressure, and uncontrolled high cholesterol When people with diabetes go untreated for years, the damage it causes almost guarantees a premature death from heart disease Diabetes also significantly raises the risk of a host of other problems These include: stroke, nerve damage neuropathy, kidney damage; damage to the eye and blindness; liver disease, impotence, poor wound healing, and susceptibility to infections that can fester and require amputations of toes, a foot, or part of a leg In addition, people with diabetes are very likely to have other dangerous health conditions One recent study found that 47 percent had two
other
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 3
heart disease risk factors such as smoking, high blood pressure, and high cholesterol and 18 percent had three or more People with uncontrolled diabetes live an average eight years less than people who do not have diabetes At greatest risk of premature disability and death are: women of all ethnic backgrounds, African Americans, Mexican Americans, American Indians, and the indigenous people of Alaska Women have the same prevalence of diabetes as men, but recent studies indicate they are much more likely to die from it Minority group members are both more prone to develop diabetes due to genetic and environmental factors and to become disabled or die from it due to multiple factors but also because they are less likely to get good care At the same time, it is important to note that all people with diabetes who receive proper and consistent care live good quality lives, and can work and function normally Type 1 and Type 2 Diabetes The Difference Confusion about diabetes is still widespread What is it and what is the difference between so-called type 1 and type 2? Diabetes is a disease
characterized by elevation of blood glucose a sugar caused by decreased production of the hormone insulin and/or increased resistance to the action of insulin by certain cells Insulin is produced in the pancreas and plays a key role in regulating the level of glucose in your blood Glucose is the bodys main fuel, and is essentially the end product of eating any carbohydrates pasta, bread, rice, grains, fruits, and vegetables Your digestive system breaks down all carbohydrates into glucose Glucose then enters the blood stream It also gets stored in the liver as glycogen, a precursor of glucose Insulin regulates both the movement of glucose into the bodys cells and the breakdown in the liver of glycogen into glucose Both actions are critical to keeping blood sugar regular and normal In type 1 diabetes usually diagnosed in childhood or the early teen years the pancreas, over a relatively brief period of time, stops producing insulin altogether The onset of the disease is usually abrupt, with severe symptoms that require immediate attention It is an autoimmune disease, which means that the part of the pancreas that produces insulin has been destroyed by errant immune cells People with
type 1 diabetes must inject insulin every day About 15 to 2 million people in the US have type 1 diabetes In type 2 diabetes, the pancreas produces enough insulin, at least in the early years that a person has the disease But for reasons that are still not well understood, the bodys cells become resistant or insensitive to it To
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Treating Type 2 Diabetes: The Oral Diabetes Drugs
compensate, the pancreas pumps out increasing amounts of insulin to normalize blood glucose levels Over time as long as a decade this everincreasing production becomes unsustainable, and the pancreas ability to produce insulin declines As a result, the telltale marker and problem of diabetes emerges: blood glucose, unable to enter the bodys cells, rises That rise leads to symptoms And when the blood sugar reaches a certain high level it appears in the urine and causes an increase in the daily volume of urine Elevated blood sugar puts a strain on almost every organ and many parts of the body Over years, it is particularly toxic to the bodys blood vessels; it causes them to thicken This leads especially to problems in the eyes and kidneys, the heart, and the blood
circulation system High blood sugar also damages the nerves Proper treatment that keeps blood sugar in the normal range sharply reduces the risk of these complications Again, there are many ideas about the causes of type 2 diabetes, and the insulin resistance that characterizes it Studies show the disease has a strong genetic hereditary component It runs in families Another cause or association is also quite clear That is overweight and obesity due in some cases to a genetic propensity to overweight and obesity but in most cases to overeating and lack of exercise About 55 percent of people diagnosed with diabetes in the US are overweight or obese While recent media attention surrounding the diabetes epidemic has focused on its link to obesity, the statistic above also means that 45 percent of people with diabetes are not overweight Symptoms and Getting Tested The symptoms of type 2 diabetes tend to develop gradually over time and include:
I I I I I I
Fatigue Frequent urination Increased thirst and hunger Blurred vision Numbness in your hands and legs Slow healing of wounds and sores
These symptoms can also be mild and/or intermittent for years If you experience any of them
and especially if you experience two or more, for even a few days you should see a doctor immediately In the early stages of the disease, symptoms may well be non-existent Thats unfortunate because the damage to organs occurs even in the
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 5
absence of symptoms For this reason, its important for people who may be at risk of diabetes to get have their blood sugar levels checked regularly Those at risk include:
I People with coronary artery disease, or vascular disease I People who have high blood pressure I People whose bad LDL cholesterol is elevated I People who are overweight or obese I Anyone with a parent or a sibling who has diabetes I People who are Black Americans, Mexican or Latino Americans, Asian
Americans, Native Americans, Pacific Islanders, or Alaskan Natives
I Women who have had diabetes during pregnancy or a baby weighing
more than 9 pounds at birth If you are in one of these groups and you have either never had a blood sugar check or the last one was done a year or more ago, you should get your blood sugar checked as soon as possible There is a disagreement in the medical community
about whether all adults should have their blood sugar checked periodically The American Diabetes Association advises that everyone aged 45 and over have a blood sugar test once every three years But the highly-regarded US Preventive Services Task Force says not enough scientific evidence exists to indicate that such broader screening has benefits or is worth the considerable cost We think the decision rests with you and your doctor and depends on an assessment of your overall health, risks, your weight, and family history Some doctors are inclined to check the blood sugars of most people over age 45 or 50, especially if they are 10 or more pounds overweight Other doctors may be more conservative Blood sugar tests are inexpensive and easy, though they may have to be done a few times to yield a conclusive diagnosis The most common one is done after an overnight fast If your blood sugar is 126 milligrams per deciliter mg/dl or greater after being checked on two or three different occasions, you are considered to have diabetes Another test assesses your blood sugar at any time not just after not eating for 8 or more hours If you have blood sugar levels of 200mg/dl or above on two or
more occasions, you are considered to have diabetes Your doctor may also talk to you about a blood test known as hemoglobin A1c pronounced hemoglobin A, one, c, and usually abbreviated in print as HbA1c and often referred to by diabetes patients as my A1c This is a commonly used test to evaluate blood sugar control after treatment is started But your doctor may order this test at the time of diagnosis Theres more about this measure in the next section
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Treating Type 2 Diabetes: The Oral Diabetes Drugs
What is Pre-Diabetes? In the last decade, doctors and researchers have recognized that a large number of people in the US have fasting blood sugar levels that are above 110mg/dl the upper limit of normal but less than the 126mg/dl required for a diagnosis of diabetes Namely, the most recent studies indicate that nearly 18 percent of the population 54 million people have what is called pre-diabetes, borderline diabetes, impaired fasting glucose, or impaired glucose tolerance What concerns doctors is that a growing body of research now shows that people with pre-diabetes a are at very high risk of developing diabetes and b at elevated risk of
heart disease and stroke even if their glucose level never rises above 125 mg/dl In the most recent analysis of this published in June 2007 people with pre-diabetes were found to have 25 times the risk of dying from heart disease over a 5-year period compared to people without diabetes The study was of 10,428 people in Australia Such findings are leading many doctors to consider drug treatment for people with pre-diabetes But most doctors agree, and good research backs it up, that dietary and lifestyle changes can be very effective for people with pre-diabetes before any medicines need to be prescribed This report does not specifically address treatment of pre-diabetes If you are diagnosed with pre-diabetes we would urge you to talk with your doctor about ways to alter your diet and lifestyle, and lose weight if you need to under a program that youll stick to Lifestyle modifications have become a mainstay of treatment for people with full-blown diabetes, too 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 The next section discusses this
further Since many people with diabetes also have high blood pressure and/or high cholesterol, your doctor will aim to get those under control, too, with diet and lifestyle changes and with medicines Oral diabetes medicines pills you take by mouth are thus just one treatment among several that doctors use to help people with diabetes and keep them healthy That said, they are a critical element of treatment Today, nine classes of drugs are available to treat type 2 diabetes That includes insulin and two other types of drugs that must be injected That leaves six categories of pills In this report we evaluate and compare all six groups, and the drugs in them We do not evaluate the injectable drugs, including the newest one, Byetta exenatide We also dont compare treatment with insulin or the other injectible drugs with pills And we do not
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 7
analyze another new diabetes drug Exubera, a form of insulin that can be inhaled Note that even though most people prefer to avoid injections, insulin and other such drugs often become necessary if diet, exercise, and pills fail to keep their blood sugar under
control Like all drugs, the names of the six diabetes drug groups and the names of the individual medicines in those groups are not easy to pronounce or remember We do our best to keep things simple but unfortunately we cant avoid using the drug category names and the names of the individual drugs The first table below presents the groups of diabetes drugs, including those now available in combination form The second table presents the individual drugs, with their generic and brand names In both, we indicate either whether the class has a generic available or whether an individual drug is available in generic form Generics are much less expensive and become available after a drug has been on the market for some 10 or more years As you can see, the sulfonylureas and metformin are older medicines now available in generic form, while the thiazolidinediones, alpha-glucosidase inhibitors, and meglitinides are newer Januvia was approved by the Food
Type of Drug
Individual Drugs Available as a Generic? Brand and generic names Brands: Amaryl, Diabeta, Glynase, Prestab, Glucotrol, Glucotrol XL, Micronase Generics: Glimepiride, Glipizide, Glyburide Brands: Glucophage, Glucophage XR,
Generics: Metformin Actos, Avandia Precose, Glyset Prandin, Starlix Januvia Brands: Glucovance, Metaglip Generics: known by generic names of the two drugs ActosPlus Met, Avandaryl, Avandamet, Duetact, Janumet
Sulfonylureas
Yes
Biguanides Thiazolidinediones Alpha-glucosidase inhibitors Meglitinides Dipeptidyl peptidase 4 inhibitors Combinations of sulfonylureas plus metformin Other Combinations
8
Yes No No No No
Yes
No
Consumer Reports Best Buy Drugs
Treating Type 2 Diabetes: The Oral Diabetes Drugs
Generic Name Thiazolidinediones Pioglitazone Rosiglitazone Meglitinides Repaglinide Nateglinide Acarbose Miglitol Biguanides Metformin Sulfonylureas Glyburide/ glibenclamide Glipizide Glimepiride Sitagliptin
Brand Name s
Available as a Generic?
Actos Avandia Prandin Starlix Precose Glyset Glucophage, Glucophage XR Diabeta, Glynase, Micronase, Prestab Glucotrol, Glucotrol XL Amaryl Januvia
No No No No No No
Alpha-glucosidase Inhibitors
Yes
Yes Yes Yes No
Dipeptidyl peptidase 4 inhibitors
XRextended release, XLlong-acting
and Drug Administration in October 2006 It is the first in a new class of diabetes drugs Our evaluation of diabetes drugs is based largely on a
thorough, independent review of the scientific research on diabetes drugs About 200 studies were closely examined out of thousands screened The review was conducted over the past 18 months by a team of physician researchers at the Johns Hopkins University Evidence-based Practice Center This team conducted the review as part of the Effective Health Care Program sponsored by the Agency for Healthcare Research and Quality, a federal agency The full report is available at wwweffectivehealthcareahrqgov/reports/ finalcfm Additional sources were used, including several to evaluate Januvia which was not addressed in the Johns Hopkins analysis Neither the Johns Hopkins University Evidence-based Practice Center nor the Agency for Healthcare Research and Quality are in any way responsible for the advice and recommendations in this report These entities also played no role in selected our Best Buy diabetes drugs; Consumers Union is solely responsible for those This report was released and last updated in July 2007
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 9
What Are the Oral Diabetes Medicines and Who Needs Them?
The six types of diabetes medicines
work in different ways But they all: a lower blood sugar levels; b help improve the bodys 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 complexity of the way the different diabetes drugs work defies simple explanation But its useful to know the basics people with diabetes who start taking a drug will need another type of drug or insulin within six years The plain fact is that most people with type 2 diabetes will eventually need to take medicine to keep their blood sugar controlled But all will also need to alter their diets and lifestyles as well losing weight if needed, dietary changes such as cutting back on carbohydrates, quitting smoking, and becoming more physically active Evidence strongly supports the additive effect of the two drugs and lifestyle changes But many studies also show conclusively that many people with diabetes can lower their blood sugar levels almost as much with modest lifestyle changes alone as with medicines, especially in the early stages of the disease Thus, given that a
all the diabetes drugs have the potential to cause adverse effects and b lifestyle changes have benefits to your health beyond controlling blood sugar, most doctors will recommend you try diet and lifestyle first before you try a drug Many people with diabetes, however, also have high blood pressure and/or elevated cholesterol, or have been diagnosed with coronary artery or vascular disease If you are in this category, your doctor may
I The sulfonylureas and meglitinides increase the I I I I
secretion of insulin by the pancreas Metformin inhibits glucose production by the liver and decreases insulin resistance The alpha-glucosidase inhibitors delay absorption of glucose by the intestine The thiazolidinediones decrease insulin resistance Januvia promotes the release of insulin from the pancreas
Since the drugs work in different ways, they are sometimes used in combination to enhance the effectiveness of treatment Indeed, 25 to 50 percent of
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Treating Type 2 Diabetes: The Oral Diabetes Drugs
Table 1 Goals for People with Diabetes
Measures Blood Sugar Fasting blood glucose Post-meal 2-hour blood glucose HemoglobinA1c HbA1c Cholesterol Total
cholesterol LDL bad cholesterol HDL good cholesterol Triglycerides Blood pressure Below 200mg/dl Below 100 mg/dl below 75 is better Above 40mg/dl for men and 50 mg/dl for women Below 150 mg/dl Below 130/80 mmHg Below 110mg/dl Below 100 is better Below 180mg/dl Below 140 or so is better Below 7 Below 65 is better Recommended Goal
Sources: American Diabetes Association; American Association of Clinical Endocrinologists; International Diabetes Federation; National Cholesterol Education Program; Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Definitions: LDL low-density lipoprotein cholesterol; HDL high-density lipoprotein cholesterol; mg milligrams; dldeciliter of blood; mmHg millimeters mercury
prescribe a diabetes drug when you are diagnosed, along with diet and lifestyle changes and classes in diabetes self-management Indeed, so many people with diabetes have other conditions and heart disease risk factors that doctors often treat them as multi-disease patients whose care and drugs must be managed particularly closely Because heart disease risks factors, including diabetes, take a cumulative toll,
medical groups and physician organizations have set aggressive goals for people with diabetes who have multiple conditions Table 1 above presents these Treatment with lifestyle changes and drugs has short-term, medium-term, and long-term goals In the short-term, it aims to get your fasting blood glucose below 110mg/dl below 100mg/dl is better and to eliminate or significantly reduce your symptoms In the medium and long-term, it aims to get your HbA1c measure down below a certain level, and keep it there As mentioned already, the HbA1c test is the one your doctor will use to track treatment success or failure It measures glucose levels chemically bound to
hemoglobin, a protein carried by red blood cells The current recommended goal for HbA1c is expressed as a percentage If you have diabetes, the magic number is 7 percent Below that is good Above it is not good Technically anything above 6 percent is considered abnormal So some doctors would rather see your HbA1c be 65 percent or lower Many studies show that an HbA1c level below 7 percent is associated with a lower risk of diabetes complications and premature death However, importantly for this report, most studies of the oral
diabetes drugs have only looked at the effects on HbA1c for a year or less Another medium-term and long-term goal of treatment is to make sure you are free of the well-known diabetes complications as time goes on This takes constant monitoring Indeed, the intensity of care needed by most people with diabetes is such that experts advise all to be cared for in formal diabetes programs Part of the purpose of such programs is to track the drugs you are taking and at what dose Your doctors and caregivers will recommend changes if your blood sugar is not controlled In fact, many doctors
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 11
Side Effects of Diabetes Drugs Most of the side effects listed here ease over time or stop when the medication is discontinued However, a few can be permanent in certain people Common I Hypoglycemia or low blood sugar usually minor if caught in time but can be serious or fatal if not treated; symptoms include profuse sweating, tremor, shakiness, dizziness, hunger When serious, includes mental confusion, coma, and a rare risk of stroke or death I Weight gain I Gastrointestinal side effects abdominal pain, nausea,
vomiting, diarrhea, gassiness, and bloating I Edema fluid in legs and ankles I Increase in bad cholesterol LDL Uncommon I Congestive heart failure I Anemia low red blood cell counts I Allergic reactions Very Rare I Thrombocytopenia low blood platelet counts I Lactic acidosis build up of acid in the blood I Leucopenia low white blood cell counts I Macular edema eye problems I Liver disease/liver failure
will encourage you to adjust the doses of your medicines based on the blood sugar readings you take yourself If you have good health insurance, diabetes selfmanagement programs are usually accessible Such programs which can be expensive usually include a dietician or nutritionist, exercise experts, and doctors that specialize in diabetes care endocrinologists
12
The team may also include a cardiologist, neurologist, ophthalmologist, kidney expert, and a foot specialist You will also get training in self-glucose monitoring and other self-care A conscientious primary care doctor whose practice has support staff with diabetes training can do just as good a job at managing people with the disease as a formal program People without insurance or those with inadequate coverage should find
such a doctor since they have limited access to formal diabetes programs Safety and Side Effects All the diabetes medicines can have adverse effects Those vary from drug class to drug class and medicine to medicine Generally, the risks posed by diabetes drugs are not an impediment to using them if you truly need one That is, for most people, the benefits of the drugs clearly outweigh the risks Even so, adverse side effects can keep people from taking their diabetes pills On average, 10 to 20 percent of people with diabetes stop taking their pills due to side effects Significant side effects occur in about 1 of every 100 people taking diabetes pills Most notably, some diabetes drugs can cause low blood sugar, or hypoglycemia This is a vexing side effect and one that often leads doctors to prescribe one diabetes drug over another The symptoms of hypoglycemia are listed in the box to the left Unfortunately, some people do not have minor symptoms to warn them that their blood sugar is getting dangerously low That is one reason your doctor will emphasize to you that you must check your blood sugar regularly The other big, worrisome side effect of some of the diabetes drugs is weight
gain, or difficulty losing weight Since many people with diabetes are trying to lose weight, this side effect can be particularly frustrating The box on this page gives a general run down of the side effects linked to diabetes drugs The potential side effects of each drug are discussed at more length in the next section, which also compares the drugs across a range of criteria including their cost and presents our Best Buys choices
Consumer Reports Best Buy Drugs
Treating Type 2 Diabetes: The Oral Diabetes Drugs
Choosing an Oral Diabetes Medicine Our
The good news is that the diabetes drugs have been compared to each other in many good studies, and some of the drugs have been used for years and helped millions of people The bad news is that most of the careful studies have not tracked people, or the long-term effects of the drugs, over many years Most followed people for just a year or less Even so, the studies help clarify the benefits and adverse effects of the drugs, and signal typical and expected effects among a group of people with diabetes But very importantly, such studies do not reveal how a specific person with diabetes will respond to a particular drug Only your
doctor and you can decide precisely which drug or drug combination is best for you given your health status, weight, other medical needs, and the severity of your diabetes Tables 2, 3 and 4 on pages 16 to 20 summarize the comparative evidence on the diabetes drugs The tables reflect an evaluation of the results from more than 200 studies Table 2 presents summary evidence of the various classes of drugs Table 3 is more specific, with detailed information on the individual drugs As such, Table 3 takes a bit more time to figure out But it contains information unique to this report and which may be valuable for your treatment decision Table 4 presents a run-down of the pros and cons of each class of diabetes The tables contain material that is duplicative On balance, though, they give you three ways of assessing the important differences among the diabetes drugs Our evaluation leads to the following overall conclusions:
Picks
I The newer drugs are no safer As discussed in the
previous section and presented in Tables 2, 3 and 4, all diabetes pills have the potential to cause adverse effects both minor and serious
I 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 As further discussed below, however, metformin can not be taken by everyone
I Taking two diabetes drugs has a positive additive
effect on reducing HbA1c This is a major plus for many people with diabetes whose blood glucose is not well controlled by a single drug The downside is that taking two drugs poses a higher risk of side effects If lower doses of each drug are used in combination, the added risk of side effects can be reduced
I The newer drugs are more expensive The newer
oral diabetes medicines cost many times more than the older ones See Table 5 As mentioned earlier, the diabetes drugs have distinctly different safety profiles Its this that may drive your and your doctors decision for initial and on-going treatment For example, the evidence clearly shows that the sulfonylureas pose a higher risk of hypoglycemia than metformin or the thiazolidinediones Avandia and Actos Between 9
and 22 percent of people taking one of the sulfonylurea drugs can expect to have an episode of potentially dangerous low blood sugar, compared to zero to 7 percent taking metformin, for example The risk of hypoglycemia is about the same for the sulfonylureas and repaglinide, but two recent studies suggest that repaglinide may cause less hypoglycemia in the elderly or in people who skip meals
I The 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
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 13
One of the newer classes of drugs poses an elevated risk of heart failure Evidence overwhelmingly indicates that the thiazolidinediones Avandia and Actos pose a 15 to 2 times increased risk of congestive heart failure compared to other diabetes medicines Between 1 and 3 in a 100 people without a history of heart disease will develop the
condition In contrast, metformin and the sulfonylureas do not raise the risk of heart failure in any significant way compared to the general risk of this condition among people with diabetes, which is higher than normal Because of the mounting evidence on this link, in May 2007 the FDA requested that the manufacturers of Actos and Avandia put a high-profile black box warning about the risk of heart failure on the labels for the two drugs If you are taking one of these medicines and have swelling of any part of your body, sudden weight gain, or breathing problems, you should contact your doctor immediately In addition, Avandia has also recently been associated with a possibly higher risk of heart attack In a study that received widespread media attention in the spring of 2007, Avandia was associated with a 43 percent greater risk of heart attack compared to other diabetes pills though the absolute risk was still a relatively low 1 to 3 in a 100 for people who had diabetes but no heart disease Notably, however, other studies comparing Avandia with other diabetes drugs or placebo have not found such a risk, and the type of study used to make the connection has limitations The upshot
is that more research is needed and no definitive conclusions can yet be reached about heart attack risks posed by Avandia If your doctor prescribes Avandia, we join other groups including the American Diabetes Association, American Heart Association, and American College of Cardiology in urging you to talk to him or her about the risks and benefits and the appropriateness of this choice If in addition to diabetes, you have multiple risk factors for heart disease, we would advise against Avandia until further studies clarify whether it poses any heightened risk of heart attack
14
Avandia also has been recently associated with an increased risk of fractures of the wrist and arm in women This unexpected finding is being further investigated and needs confirmation As good as it looks in other ways, metformin has been associated with rare occurrences of lactic acidosis the build up of lactic acid in the blood, which can lead to severe consequences This rare risk appears to exist mostly for diabetics who also have moderate kidney disease and/or heart failure As a result, such patients should not be prescribed metformin Minor but annoying side effects may also play a role in your
choice of a diabetes medicine For example, gastrointestinal 
side effects including bloating, gas, nausea, and diarrhea are more frequent with metformin and particularly with acarbose than the other drugs Our Picks and Recommendations Taking effectiveness, safety, side effects, dosing, and cost into consideration, we have chosen the following as Consumer Reports Best Buy Drugs if your doctor has decided that you need medicine to control your diabetes:
I Metformin alone or in combination with glipizide or glimepiride
I Glipizide and Glipizide Sustained Release alone
or in combination with metformin
I Glimepiride alone or in combination with metformin All these medicines are available as low-cost generics, either alone or in combination See Table 5 In recent years, a strong medical consensus has emerged in the US, Europe, and Australia that most newly diagnosed people with diabetes who need a medicine should first be prescribed metformin alone Based on the systematic evaluation of diabetes drugs that forms the basis for this report, we concur with that advice: metformin first, unless your health status prevents it If metformin fails to bring your blood
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Treating Type 2 Diabetes: The Oral Diabetes Drugs
glucose into normal range, you may need a second drug Most commonly that should be one of two other Best Buys we have chosen above Should either of those trigger hypoglycemia, Actos may be an option you and your doctor will want to consider If you are unable to take metformin or do not tolerate it well, you face a choice of one of the sulfonylureas or a newer medicine Despite the elevated risk of hypoglycemia, we recommend trying glipizine or glimepiride If either of those triggers hypoglycemia, talk with your doctor about Actos If glipizide, glimepiride, or Actos alone fail to bring your blood glucose into control and keep your HbA1c below 7 percent, your doctor will likely recommend a second drug If upon initial diagnosis your glucose and HbA1c are quite high, you may be prescribed a combination of two drugs at the beginning of treatment usually metformin plus a sulfonylurea Another option would be metformin plus Actos Avandia may still be a viable option for some people But as indicated above, its present disadvantages compel a clear rationale for its choice, either as a solo treatment or in combination with another
drug If your doctor prescribes Avandia as the first drug
you take after diagnosis, you should question that decision There are some clinical circumstances in which this would be a wise choice, but only for a small percentage of people Unfortunately, Actos and Avandia have been heavily promoted to doctors and consumers in the US As a result, both drugs have been over-prescribed to people who should instead be taking metformin and/or a sulfonylurea Both drugs have been marketed specifically to minorities as well, but there is no good evidence that any diabetes medicine is more effective or safer in African-Americans and Hispanic or American Indian patients than in others Januvia is a promising new addition to the diabetes medicine cabinet But it has not yet been well studied It is not as effective at lowering blood glucose and HbA1c as other diabetes drugs, but it has not been linked to date with weight gain or hypoglycemia either - a plus Until it has been better studied and prescribed more broadly over a longer period, we would not advise it as a first-line drug It is also expensive Finally, as a reminder, if your diabetes is not controlled by pills, you may have to take insulin
or one of the other drugs available by injection only
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 15
Table 2 Summary of Comparative Effectiveness of Diabetes Drugs
Outcome
Sulfonylureas vs Metformin
Sulfonylureas vs Thiazolidinediones
Sufonylureas vs Meglitinide1
Metformin vs Thiazolidinediones
Hemoglobin A1c Weight Blood Pressure LDL bad cholesterol HDL good cholesterol
No difference Metformin better No difference Metformin better
No difference No difference No difference Sulfonylureas better
No difference No difference Not enough evidence No difference
No difference Metformin better No difference Metformin better Thiazolidinediones better One thiazolidinedione better3 No difference Thiazolidinediones better
No difference
Thiazolidinediones better
No difference
Triglycerides
Metformin better
No difference2
No difference
Risk of Hypoglycemia
Metformin better
Thiazolidinediones better
No difference
Risk of GI problems
Sulfonylureas better
Not enough evidence
Not enough evidence
Risk of Congestive Heart Failure Risk of Anemia Risk of Edema fluid build-up
No difference
Sulfonylureas better
Not enough
evidence
Metformin better
Not enough evidence
Sulfonylureas better
Not enough evidence
Metformin better
Not enough evidence
Sulfonylureas better
Not enough evidence
Metformin better
Source: Bolen S, et al, Comparative Effectiveness and Safety of Oral Diabetes Medications for Adults with Type 2 Diabetes http://wwweffectivehealthcareahrqgov Definitions: No difference means that adequate or good studies have been done and when considered as a whole have found no difference between these two categories of drugs Not enough evidence means not enough studies have been done, or the studies that have been done are not good enough to warrant a judgment about any differences between these two classes of drugs 1 For repaglinide only 2 Pioglitizone Actos decreased triglycerides while rosiglitizone Avandia increased triglycerides; thus, Actos showed similar effects to the sulfonylureas while Avandia was worse than the sulfonylureas But no direct comparisons were available to draw firm conclusions 3 Pioglitizone Actos was better than metformin while rosiglitizone Avandia was worse
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Consumer Reports Best Buy Drugs
Treating Type 2 Diabetes: The Oral Diabetes Drugs
Table 3
Effects of Diabetes Drugs on Specific Measures
A down arrow M means a decrease or decline; an up arrow L means increase; and a diamond N means no meaningful effect or change IE Insufficient Evidence Brand names are not given for drugs available as generics Average point reduction HbA1c percent Average point change in blood pressure mmHg Average absolute change in LDL cholesterol mg/dL Average absolute change in HDL cholesterol mg/dL Average absolute change in Triglycerides mg/dL Risk of Hypoglycemia of people1 Average change in weight lbs
Sulfonylureas Glyburide Glipizide Glimepiride Biguanides Metformin
M 09-14 N L 5-7 N M 15-25 M 13-18 M 13-18 M 13-18 N N N N N N N N N M 10-20 M 10-20 M 10-20
10-22 10-15 9-14
L 5-10 L 5-10 L 5-10
0-7
N
Thiazolidinediones Pioglitazone Actos Rosiglitazone Avandia Meglitinides Repaglinide Prandin Nateglinide Starlix
M 08-20 M 03-08 M 08-12 M 09-14 N L 8-12 L 12-15 L5 L3 M 35-45 L 10-20
0-3 4-11
L 5-10 L 5-10
N
IE2 IE
N
N
M 10-15
11-32 133
L 5-10
IE
IE
IE
IE
Alpha-glucosidase inhibitors Acarbose4 Precose Miglitol4 Glyset
M 06-09 M 04-09
IE IE
N
N
M 10-15
0-5 IE
N
IE
IE
IE
IE
Dipeptidyl peptidase 4 inhibitor
Sitagliptin5 Januvia
M 06-08
IE
N
N
N
Low
N
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 17
Table 3 Effects of Diabetes Drugs on Specific Measures continued
A down arrow M means a decrease or decline; an up arrow L means increase; and a diamond N means no meaningful effect or change IE Insufficient Evidence Brand names are not given for drugs available as generics Average point reduction HbA1c percent Selected Combinations Metformin sulfonylurea Glucovance, Metaglip Metformin rosiglitazone Avandamet Average point change in blood pressure mmHg Average absolute change in LDL cholesterol mg/dL Average absolute change in HDL cholesterol mg/dL Average absolute change in Triglycerides mg/dL Risk of Hypoglycemia of people1 Average change in weight lbs
M 17-23
IE
M 5-7
N
M 20-40
14-28
L 5-10
M 13-20
IE
L 12-15
L3
N
0-7
L 5-10
Sulfonylurea M 17-23 rosiglitazone Avandaryl
IE
L 10-12
L3
N
18-30
L 5-10
Source: Bolen S, et al, Comparative Effectiveness and Safety of Oral Diabetes Medications for Adults with Type 2 Diabetes http://wwweffectivehealthcareahrqgov Definitions/Key: N No meaningful change; M Significant
decrease; L Significant increase; IEinsufficient data; lbspounds; mg/dlmilligrams per deciliter of blood; mmHgmillimeters mercury; HbA1chemoglobin A1c; LDLlow-density lipoprotein cholesterol; HDL high-density lipoprotein cholesterol 1 Results mostly come from short-duration studies lasting 3 months to 1 year There are only a few studies longer than one year which show slightly higher rates of hypoglycemia but similar comparative results 2 IE insufficient evidence for this drug on this measure to reach any meaningful conclusions 3 Results based on one short-term study 1 year 4 Results are based on data from a systematic review plus a large randomized study 5 Preliminary data based on product label and a monograph by the Veterans Administrations national pharmacy service
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Consumer Reports Best Buy Drugs
Treating Type 2 Diabetes: The Oral Diabetes Drugs
Table 4 Advantages and Disadvantages of the Diabetes Drugs
Advantages: Disadvantages:
The sulfonylureas glyburide, glimepiride, glipizide - Fast onset of action - No effect on blood pressure - No effect on LDL cholesterol - Convenient dosing - Low cost - Weight gain 5 to 10 pounds on average - Heightened risk of
hypoglycemia - Glyburide has slightly higher risk of hypoglycemia compared with glimepiride and glipizide
Metformin - Low risk of hypoglycemia - Not linked to weight gain - Good effect on LDL cholesterol - Good effect on triglycerides - No ill effect on blood pressure - Low cost - Higher risk of GI side effects nausea and diarrhea - Can not be taken by people with diabetes who have moderate kidney disease or heart failure because of risk of lactic acid build-up - Less convenient dosing
The alpha-glucosidase inhibitors acarbose, miglitol - Slightly lower risk of hypoglycemia compared to sulfonylureas - Not associated with weight gain - Decreases triglycerides - No adverse effects on cholesterol - Less effective than most other diabetes pills in lowering HbA1c - Higher risk of GI side effects than other diabetes pills except metformin - Inconvenient dosing - High cost
The thiazolidinediones Actos, Avandia - Low risk of hypoglycemia - Slight increase in good HDL cholesterol - Actos linked to decreased triglycerides - Convenient dosing - Higher risk of heart failure - Weight gain 5 to 10 pounds - Link to higher risk of edema fluid build-up - Link to higher risk of anemia - Increase
in bad LDL cholesterol - Avandia linked to increased triglycerides and possibly not yet confirmed higher risk of heart attack - Slower onset of action - Rare risk of liver problems; required monitoring - High cost
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 19
Table 4 Advantages and Disadvantages of the Diabetes Drugs
Advantages: Disadvantages: The meglitinides nateglinide, repaglinide - No bad effect on cholesterol - Rapid onset of action - Repaglinide associated with risk of hypoglycemia and weight gain similar to the sulfonylureas - Nateglinide has less effect on HbA1c - Inconvenient dosing - High cost Januvia sitagliptin - Apparent low risk of hypoglycemia - Few known side effects but new drug - No weight gain - Convenient dosing - Reduces HbA1c less than several other diabetes drugs - May only be valuable as a second drug; use as the first drug only if unable to take other diabetes drugs, until further research is conducted - Less data on potential side effects compared to older drugs - High cost
This is a new drug approved in October 2006 There is less research and experience with it than with other diabetes medicines In addition,
no studies have followed patients taking it for longer than one year Sources: 1 Bolen S, et al, Comparative Effectiveness and Safety of Oral Diabetes Medications for Adults with Type 2 Diabetes http://wwweffectivehealthcareahrqgov; 2Oral hypoglycemics in the treatment of type 2 diabetes; Therapeutic Insights American Medical Association June 2007; Januvia labeling and available material
20
Consumer Reports Best Buy Drugs
Treating Type 2 Diabetes: The Oral Diabetes Drugs
Table 5: Cost of Diabetes Drugs
Generic Name and Dose Glyburide 5 mg tablet Glyburide 5 mg tablet Glyburide 5 mg tablet Glyburide 5 mg tablet 25 mg tablet Glyburide 5 mg tablet 25 mg tablet Glyburide 5 mg tablet 25 mg tablet Glyburide 5 mg tablet Glyburide 5 mg tablet Glyburide 5 mg tablet Glyburide micronized 3 mg tablet Glyburide micronized 3 mg tablet Glyburide micronized 6 mg tablet Glyburide micronized 6 mg tablet Glyburide micronized 6 mg tablet 15 mg tablet Glyburide micronized 6 mg tablet 15 mg tablet Glipizide 5 mg tablet Glipizide 5 mg tablet Glipizide 10 mg tablet Glipizide 10 mg tablet Brand Name or Generic Generic Micronase Diabeta Generic Micronase Diabeta Generic Micronase Diabeta
Glynase Generic Glynase Generic Number of Pills Per day1 One One One One One One Two Two Two One One One One Total Daily Dose1 5 mg 5 mg 5 mg 75 mg 75 mg 75 mg 10 mg 10 mg 10 mg 3 mg 3 mg 6 mg 6 mg Average Monthly Cost2 12 41 31 23 69 39 81 62 42 12 66 19
Glynase
One
75 mg
89
Generic
One
75 mg
29
Glucotrol Generic Glucotrol Generic
One One One One
5 mg 5 mg 10 mg 10 mg
22 9 34 11
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 21
Table 5: Cost of Diabetes Drugs continued
Generic Name and Dose Glipizide 10 mg tablet Glipizide 10 mg tablet Glipizide 5 mg tablet, sustained release Glipizide 5 mg tablet, sustained release Glipizide 5 mg 25 mg tablets, sustained release Glipizide 5 mg 25 mg tablets, sustained release Glipizide 10 mg tablet, sustained release Glipizide 10 mg tablet, sustained release Glipizide 10 mg 5 tablets, Sustained Release Glipizide 10 mg 5 tablets, sustained release Glipizide 10 mg tablets, sustained release Glipizide 10 mg tablets, sustained release Glimepiride 1 mg tablet Glimepiride 1 mg tablet Glimepiride 2 mg tablet Brand Name or Generic Glucotrol Generic Glucotrol Generic Glucotrol Number of Pills Per day1
Two Two One One One Total Daily Dose1 20 mg 20 mg 5 mg 5 mg 75 mg Average Monthly Cost2 68 22 22 14 to 17 43
Generic
One
75 mg
28
Glucotrol Generic
One One
10 mg 10 mg
39 23 to 29
Glucotrol
One
15 mg
61
Generic
One
15 mg
43
Glucotrol
Two
20 mg
78
Generic
Two
20 mg
46 to 58
Amaryl Generic Amaryl
One One One
1 mg 1 mg 2 mg
20 12 29
22
Consumer Reports Best Buy Drugs
Treating Type 2 Diabetes: The Oral Diabetes Drugs
Table 5: Cost of Diabetes Drugs continued
Generic Name and Dose Glimepiride 2 mg tablet Glimepiride 4 mg tablet Glimepiride 4 mg tablet Metformin 500 mg tablet Metformin 500 mg tablet Metformin 1000 mg tablet Metformin 1000 mg tablet Metformin 1000 and 500 mg tablets Metformin 1000 and 500 mg tablets Metformin 850 mg tablet Metformin 850 mg tablet Sitagliptin 100 mg tablet Sitagliptin 50 mg tablet Pioglitazone 15 mg tablet Pioglitazone 30 mg tablet Pioglitazone 45 mg tablet Rosiglitazone 2 mg tablet Brand Name or Generic Generic Amaryl Generic Glucophage Generic Glucophage Generic Glucophage Generic Glucophage Generic Number of Pills Per day1 One One One Three Three Two Two Three Three Three Three Total Daily Dose1 Average Monthly Cost2
18 51 27 102 38 134 45 168 58 167 60
2 mg 4 mg 4 mg 1500 mg 1500 mg 2000 mg 2000 mg 2550 mg 2500 mg 2550 mg 2550 mg
Januvial Januvia
One One
100 mg 50 mg
208 201
Actos Actos Actos Avandia
One One One Two
15 mg 30 mg 45 mg 4 mg
142 221 241 180
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 23
Table 5: Cost of Diabetes Drugs continued
Generic Name and Dose Rosiglitazone 4 mg tablet Rosiglitazone 4 mg tablet Rosiglitazone 8 mg tablet Repaglinide 1 mg tablet Repaglinide 1 mg and 05 mg tablet Repaglinide 2 mg tablet Nateglinide 60 mg tablet Nateglinide 120 mg tablet Acarbose 50 mg tablet Acarbose 50 mg plus 25 mg tablets Acarbose 100 mg tablet Miglitol 50 mg tablet Miglitol 50 mg plus 25 mg tablets Miglitol 100 mg tablet Metforminglipizide 250 mg/25 mg Metforminglipizide 250 mg/25 mg Metforminglipizide 500 mg/25 mg Metforminglipizide 500 mg/25 mg Brand Name or Generic Avandia Avandia Avandia Number of Pills Per day1 One Two One Total Daily Dose1 Average Monthly Cost2 131 262 233
4 mg 8 mg 8 mg
Prandin Prandin Prandin Starlix Starlix Precose Precose Precose Glyset Glyset Glyset Metaglip Generic Metaglip Generic
24
Three Three Three
Three Three Three Three Three Three Three Three Two Two Two Two
3 mg 45 mg 6 mg 180 mg 460 mg 150 mg 225 mg 300 mg 150 mg 225 mg 300 mg 250/25-500/5 mg 500/5 mg 1000/5 mg 1000/5 mg
162 321 156 157 162 106 210 124 99 195 113 71 57 78 63
Consumer Reports Best Buy Drugs
Treating Type 2 Diabetes: The Oral Diabetes Drugs
Table 5: Cost of Diabetes Drugs continued
Generic Name and Dose Metforminglipizide 500 mg/5 mg Metforminglipizide 500 mg/5 mg Metforminglyburide 250 mg/125 mg Metforminglyburide 250 mg/125 mg Metforminglyburide 500 mg/25 mg Metforminglyburide 500 mg/25 mg Metforminglyburide 500 mg/5 mg6 Metforminglyburide 500 mg/5 mg6 Pioglitazone metformin 15mg/ 850 tablet Pioglitazone metformin 15mg/ 500 tablet Pioglitazone metformin 15mg/ 850 tablet Rosiglitazone glimepiride 4mg/ 1 mg tablet Rosiglitazone glimepiride 4mg/ 2 mg tablet Rosiglitazone glimepiride 4mg/ 4 mg tablet Rosiglitazone glimepiride 4mg/ 8 mg tablet Brand Name or Generic Metaglip Generic Glucovance Generic Glucovance Generic Glucovance Generic Actoplus Met Number of Pills Per day1 Two Two Two Two Two Two Three Three One Total Daily Dose1 Average Monthly Cost2 79 62 72 44 86 47 129 71 105
1000/10 mg 1000/10
mg 500/25 mg 500/25 mg 1000/5 mg 1000/5 mg 1500/15 mg 1500/15 mg 850/15 mg
Actoplus Met
Two
1000/30 mg
206
Actoplus Met
Two
1500/45 mg
210
Avandaryl
One
4/1 mg
144
Avandaryl
One
4/2 mg
150
Avandaryl
One
4/4 mg
148
Avandaryl
One
4/4 mg
148
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 25
Table 5: Cost of Diabetes Drugs continued
Generic Name and Dose Rosiglitazone metformin 1 mg/ 500 mg Rosiglitazone metformin 1 mg/ 500 mg Rosiglitazone metformin 2 mg/ 500 mg Rosiglitazone metformin 4 mg/ 1000 mg Sitagliptin metformin 50/500 Sitagliptin metformin 50/1000 Brand Name or Generic Number of Pills Per day1 Total Daily Dose1 Average Monthly Cost2
Avandamet
Two
2/1000 mg
83
Avandamet
Two
4/1000 mg
152
Avandamet
Two
4/2000 mg
161
Avandamet
Two
8/2000 mg
262
Janumet Janumet
Two Two
100/1000 100/1000
106 104
1 As commonly or usually recommended 2 Prices reflect nationwide retail average for May 2007, rounded to the nearest dollar Information derived by Consumer Reports Best Buy Drugs from data provided by Wolters Kluwer Health, Pharmaceutical Audit Suite
26
Consumer Reports Best Buy Drugs
Treating
Type 2 Diabetes: The Oral Diabetes Drugs
Best Buy Drug Recommendations Talking With Your Doctor
Its important for you to know that the information we present in this report is not meant to substitute for a doctors judgment But we hope it will help your doctor and you arrive at a decision about which diabetes drug and at what dose is best for you Bear in mind that many people are reluctant to discuss the cost of medicines with their doctors and that studies show doctors do not routinely take price into account when prescribing medicines Unless you bring it up, your doctors may assume that cost is not a factor for you Many people including many physicians also believe that newer drugs are always or almost always better While thats a natural assumption to make, the fact is that its not true Studies consistently show that many older medicines are as good as, and in some cases better than, newer medicines Think of them as tried and true, particularly when it comes to their safety record Newer drugs have not yet met the test of time, and unexpected problems can and do crop up once they hit the market Of course, some newer prescription drugs are indeed more effective and safer Talk with
your doctor about the pluses and minuses of newer versus older medicines, including generic drugs Prescription medicines go generic when a companys patents on a drug lapse, usually after about 12 to 15 years At that point, other companies can make and sell the drug Generics are almost always much less expensive than newer brand name medicines, but they are not lesser quality drugs Indeed, most generics remain useful medicines even many years after first being marketed That is why today about half of all prescriptions in the US are for generics Another important issue to talk with your doctor about is keeping a record of the drugs you are taking There are several reasons for this: First, if you see several doctors, they may not always tell each other which drugs have been prescribed for you Second, it is very common for doctors today to prescribe several medicines for you before finding one that works well or best, mostly because people vary in their response to prescription drugs Third, more and more people today take several prescription medications, nonprescription drugs and supplements all at the same time Many of these interact in ways that can be very dangerous And fourth, the
names of prescription drugs–both generic and brand–are often hard to pronounce and remember For all these reasons, its important to keep a list of the drugs you are taking, both prescription and nonprescription and including dietary supplements Always be sure, too, that you understand the dose of the medicine being prescribed for you and how many pills you are expected to take each day Your doctor should tell you this information When you fill a prescription at the pharmacy, or if you get it by mail, you may want to check to see that the dose and the number of pills per day on the pill bottle match the amounts that your doctor told you
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 27
How We Conducted Our Review of the Diabetes Drugs
Our evaluation is based in large part on an independent review of the scientific evidence on the effectiveness, safety, and adverse effects of the oral diabetes medicines conducted by the Johns Hopkins Universityevidence based Practice Center under contract number 290-02-0018 with the Agency for Healthcare Research and Quality This analysis reviewed hundreds of studies, including those conducted by the drugs
manufacturers A synopsis of the results of this analysis, written by the researchers at Johns Hopkins, forms the basis for portions of this report However, no statement in this report should be construed as the official position of the Johns Hopkins Evidence-based Practice Center, the Agency for Healthcare Research and Quality, or the US Department of Health and Human Services In particular, none of those entities played any role in our selection of the Best Buy diabetes drugs Consumers Union and Consumer Reports Best Buy Drugs is solely responsible for those, and for all other specific advice and recommendations in this report Additional sources were also used in writing this report Those include:
I Selected recent articles in peer-reviewed journals
See References The prescription drug costs we site were obtained from a healthcare information company that tracks the sales of prescription drugs in the US Prices for a drug can vary quite widely, even within a single city or town All the prices in this report are national averages based on sales of prescription drugs in retail outlets They reflect the cash price paid for a months supply of each drug in May 2007 Consumers Union and
Consumer Reports selected the Best Buy Drugs using the following criteria The drug had to:
I Be as effective or more effective than other oral
diabetes medicines
I Have a safety record equal to or better than other
diabetes medicines
I Cost roughly the same or less than other diabetes
medicines The Consumers Reports Best Buy Drugs methodology is described in more detail in the methods section at wwwCRBestBuyDrugsorg
I An analysis of selected classes of diabetes drugs
conducted by the Drug Effectiveness Review Project DERP, a 15-state initiative to evaluate the comparative effectiveness and safety of hundreds of prescription drugs
I The results of three recent reviews of oral diabetes drugs by the Cochrane Collaboration
I An American Medical Association monograph
on the oral diabetes drugs
I Diabetes: Treatment Options Report, an April
2006 publication released by the California HealthCare Foundation and prepared by the University of California, Davis Center for Health Services Research in Primary Care
I A Veterans Administration monograph on diabetes drugs
I Recent guidelines issued by the American Diabetes
Association and American College of Cardiology
28
Consumer
Reports Best Buy Drugs
Treating Type 2 Diabetes: The Oral Diabetes Drugs
About Us
Consumers Union, publisher of Consumer Reports magazine, is an independent and nonprofit organization whose mission since 1936 has been to provide consumers with unbiased information on goods and services and to create a fair marketplace Its website is wwwconsumerorg The magazines website is wwwconsumerreportsorg Consumer Reports Best Buy Drugs is a public education project administered by Consumers Union Two outside sources of generous funding made the project possible They are a major grant from the Engelberg Foundation, a private philanthropy, and a supporting grant from the National Library of Medicine, part of the National Institutes of Health A more detailed explanation of the project is available at wwwCRBestBuyDrugsorg We followed a rigorous editorial process to ensure that the information in this report and on the Consumer Reports Best Buy Drugs website is accurate and describes generally accepted clinical practices If we find, or are alerted to, an error, we will correct it as quickly as possible However, Consumer Reports and its authors, editors, publishers, licensors and any suppliers
cannot be responsible for medical errors or omissions, or any consequences from the use of the information on this site Please refer to our user agreement at wwwCRBestBuyDrugsorg for further information Consumer Reports Best Buy Drugs should not be viewed as a substitute for a consultation with a medical or health professional This report and the information on wwwCRBestBuyDrugsorg are provided to enhance your communication with your doctor, rather than to replace it
Sharing this Report
This copyrighted report can be freely downloaded, reprinted and disseminated for individual noncommercial use without permission from Consumers Union or Consumer Reports magazine as long as it clearly attributed to Consumer Reports Best Buy Drugs We encourage its wide dissemination as well, for the purpose of informing consumers However, Consumers Union does not authorize the use of its name or materials for commercial, marketing, or promotional purposes Any organization interested in broader distribution of this report should contact Wendy Wintman at wintwe@consumerorg Consumer Reports Best Buy Drugs is a trademarked property of Consumers Union All quotes from the material should site Consumer
Reports Best Buy Drugs as the source Consumers Union 2007
Treating Type 2 Diabetes: The Oral Diabetes Drugs Consumer Reports Best Buy Drugs 29
References
1 Bolen S, et al, Comparative Effectiveness and Safety of Oral Diabetes Medications for Adults with Type 2 Diabetes July 2007 Report sponsored by the Agency for Healthcare Research and Quality Available at: wwweffectivehealthcare ahrqgov/reports/finalcfm Bolen S, et al, Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus, Ann of Int Med September 18, 2007; Web published in advance of print publication, July 16, 2007 Available at wwwannalsorg/cgi/content/full/ 0000605-200709180-00178V1 Standards of Medical Care in Diabetes2007, American Diabetes Association Position Statement Diabetes Care 2007 30: S4-S41 Cutler, ED and Prescott, P, Diabetes: Treatment Options Report April 2006 Reports prepared for the California HealthCare Foundation wwwchcforg Oral Hypoglycemics in the Treatment of Type 2 Diabetes, American Medical Association Therapeutic Insights June 2007 American Diabetes Association: Diagnosis and Classification of Diabetes Mellitus Diabetes Care 2007 30: S42-47 All
About Diabetes, American Diabetes Association Accessed July 2, 2007 http://wwwdiabetesorg/about-diabetesjsp Guidelines for Clinical Practice for the Management of Diabetes Mellitus, American Association of Clinical Endocrinologists, American College of Endocrinology, The American Association of Clinical Endocrinologists Medical May/June 2007 Available at wwwaacecom/pub/pdf/guidelines/DMGuidelines2007pdf National PBM Drug Monograph Sitagliptin Januvia, November 2006; Veterans Administration Pharmacy Benefit Management Strategic Health Care Group Available at wwwpbmvagov/monograph/sitagliptinpdf 22 Sitagliptin/Metformin Janumet for Type 2 Diabetes, The Medical Letter on Drugs and Therapeutics June 4, 2007: Vol 49, Issue 1262, page 1 23 Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes, The UK Prospective Diabetes Study Group Lancet 1998: Vo 352 9131, pages 837-853 24 A randomized trial of efficacy of early addition of metformin in sulfonylureatreated type 2 diabetes The UK Prospective Diabetes Study Group Diabetes Care 1998: Vol 21 1, pages 87-92 25 Third Report of the
National Cholesterol Education Program NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Adult Treatment Panel III, Circulation 2002: Vol 10625, pages 3143-3421 26 Global guidelines for type 2 diabetes: recommendations for standard, comprehensive, and minimal care Diabetes Med 2006; Vol 236, pages 579-593 27 Chobanian, AV et al, The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 Report JAMA 2003: Vol 28919, pages 2560-2572 28 Holman RR, et al, A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years, The UK Prospective Diabetes Study Diabetes Care 1999: Vol 226, pages 960-964 29 Inzucchi SE, et al, Oral antihyperglycemic therapy for type 2 diabetes: scientific review, JAMA 2002: Vol 2873, pages 360-372 30 Salpeter S, et al, Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus, Cochrane Database Sys Rev 20061 31 Van de Laar FA, et al, Alpha-glucosidase inhibitors for people with impaired glucose tolerance or impaired fasting blood glucose Cochrane Database Syst Rev
20064 32 Nesto RW, et al Thiazolidinedione use, fluid retention, and congestive heart failure: A consensus statement from the American Heart Association and American Diabetes Association Circulation December 9, 2003: Vol108, pages 2941-2948 33 Nissen SE, et al, Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes, N Engl J Med 2007 Vol 356, pages 24572471 34 Kahn SE, et al, ADOPT Study Group: Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy N Engl J Med 2006: Vol 355, pages 24272443 35 Home PD, et al, Rosiglitazone evaluated for cardiovascular outcomes an interim analysis, N Engl J Med 2007 36 Goldstein BJ et al, Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes Diabetes Care May 7, 2007 E-pub ahead of print 37 Dormandy JA, et al Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study a randomised controlled trial Lancet 2005: Vol 366 9493, pages 1279-89 38 Papa G, et al, Safety of type 2 diabetes treatment with repaglinide compared with glibenclamide in
elderly people: a randomized, open-label, two-period, crossover trial Diabetes Care 2006: Vol 29, pages 1918-1920 39 Damsbo, P et al, A double-blind randomized comparison of meal-related glycemic control by repaglinide and glyburide in well-controlled type 2 diabetic patients, Diabetes Care 1999: Vol22, pages 789-94 40 Vijan, S et al, Estimated benefits of glycemic control in microvascular complications in type 2 diabetes, Ann Intern Med 1997: Vol 127, pages 788-795 41 Stettler C et al, Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: meta-analysis of randomized trials, Am Heart J 2006: Vol 152, pages 27-38
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3 4 5 6 7 8
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and women with diabetes, 1971-2000, Annals of Internal Med June 18, 2007 Published online; print version dated August 7, 2007; Vol 147, No 3 15 Burnet, DL et al, Preventing diabetes in the clinical setting, J Gen Int Med 2006 Vol 21, pages 84-93 16 Franco, OH et al, Associations of diabetes mellitus with total life expectancy and life expectancy with and without cardiovascular disease, Arch Internal Med June 11, 2007 Vol 167, pages 1145-1151 17 Barr, EL et al, Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose and impaired glucose tolerance, The Australian Diabetes, Obesity, and Lifestyle Study Circulation July 10, 2007 Vol 116 18 Hampton, T, Diabetes drugs tied to fractures in women, JAMA April 18, 2007: Vol 297, No 15, page 1645 19 Mitka, M, Report quantifies diabetes complications, JAMA June 6, 2007: Vol 297, No 21, pages 2337-2338 20 Dabelea, D et al, Incidence of diabetes in youth in the United States, JAMA June 27, 2007: Vol 297, No 24, pages 2716-2724 21 Amori, RE et al, Efficacy and safety of incretin therapy in type 2 diabetes systematic review and meta-analysis, JAMA July 11, 2007: Vol 298, No 2, pages
194-206
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Treating Type 2 Diabetes: The Oral Diabetes Drugs
Source:house.gov
