Type 2 diabetes is among the most severe medical conditions impacting our country today. The variety of individuals who have it has been increasing alarmingly.
Type 2 diabetes used to be described as “adult onset” diabetes, but not. In the last few years, the occurrence amongst children and adolescents has exploded. Much of that surge is due to the remarkable boost in the last 20 years in the number of youths who are physically inactive and obese or obese.
This article compares the efficiency, safety, and cost of medications used to treat type 2 diabetes. It belongs to a Consumer Reports task to assist you find safe, effective medications that give you the most worth for your health-care dollar. For more information about the project and other drugs we’ve evaluated for other illness and conditions, go to www.CRBestBuyDrugs.org.
Choosing an Oral Diabetes Medicine
The bright side is that the diabetes drugs have been compared with each other in many excellent research studies, and some of the drugs have actually been used for many years and helped millions of people. The bad news is that the majority of the cautious research studies have actually not tracked the impacts of the drugs (advantages and disadvantage) over several years. Many followed individuals for simply a year or less.
Nevertheless, the research studies assist clarify the benefits and adverse results of most diabetes drugs, and signal typical and predicted impacts amongst a group of individuals with diabetes. But extremely importantly, such studies do not expose how a specific person with diabetes will respond to any particular drug. Only your doctor and you can choose precisely which drug or drug combination is best for you given your health status, weight, other medical requirements, and the seriousness of your diabetes. And only you and your doctor can track how well a specific drug or combination of drugs is helping you, or not assisting you.
Tables 1, 2, and 3, respectively, summarize the relative proof on the diabetes drugs. The tables reflect the arise from 166 research studies. Table 1 presents summary proof of the different classes of diabetes drugs. Table 2 is more specific, with comprehensive details on the individual drugs. As such, Table 2 takes a bit more time to find out. However it consists of details unique to this report and which may be valuable for your treatment choice.
Table 1. Summary of Comparative Effectiveness of Oral Diabetes Drugs
|Outcome||Sulfonylureas vs. Metformin||Sulfonylureas vs. Thiazoli-dinediones||Sufonylureas vs. Meglitinide1||Sulfonylureas vs. DPP-inhibitors||Metformin vs. Thiazoli-dinediones||Metformin vs. DPP-inhibitors|
|Hemoglobin A1c||No difference||No difference||No difference||Sulfonylureas better||No difference||Metformin better|
|Weight||Metformin better||Sulfonylureas better||No difference||Not enough evidence||Metformin better||Metformin better|
|Blood Pressure||No difference||No difference||Not enough evidence||Not enough evidence||No difference||Not enough evidence|
|LDL (bad) cholesterol||Metformin better||Sulfonylureas better||No difference||Not enough evidence||Metformin better||Metformin better|
|HDL (good) cholesterol||No difference||Thiazoli-dinediones better||No difference||Not enough evidence||Thiazoli-dinediones better4||Not enough evidence|
|Triglycerides||Metformin better||No difference2||No difference||Not enough evidence||One thiazoli-dinedione better3||Not enough evidence|
|Risk of Hypoglycemia||Metformin better||Thiazoli-dinediones better||No difference||DPP-inhibitors better||No difference||Not enough evidence|
|Risk of GI problems||Sulfonylureas better||Not enough evidence||Not enough evidence||Not enough evidence||Thiazoli-dinediones better||DPP-inhibitors better|
|Risk of Congestive Heart Failure||No difference||Sulfonylureas better||Not enough evidence||Not enough evidence||Metformin better||Not enough evidence|
|Risk of Anemia||Not enough evidence||Sulfonylureas better||Not enough evidence||Not enough evidence||Metformin better||Not enough evidence|
|Risk of Edema (fluid build-up)||Not enough evidence||Sulfonylureas better||Not enough evidence||Not enough evidence||Metformin better||Not enough evidence|
|Risk of Bone Fractures||Not enough evidence||Not enough evidence||Not enough evidence||Not enough evidence||Metformin better||Not enough evidence|
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.
- For repaglinide (Prandin) only.
- Pioglitazone (Actos) decreased triglycerides while rosiglitazone (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.
- Pioglitazone (Actos) was better than metformin while rosiglitazone (Avandia) was worse.
- Pioglitazone was better than metformin.
Table 3 provides a run-down of the advantages and disadvantages of each drug class. The tables consist of some product that is duplicative. On balance, though, they give you three ways to examine the essential distinctions amongst diabetes drugs.
Evaluation leads to the following overall conclusions:
- The newer drugs are no better. The thiazolidinediones, meglitinides, alpha-glucosidase in hibitors, and dipeptidyl peptidase 4 inhibitors (all more just recently established) disappear efficient than the sulfonylureas and metformin (which have been around for years). In fact, four of the more recent medicines – acarbose, miglitol, nateglinide, and sitagliptin – reduce HbA1c less than the other drugs.
- The more recent drugs are no much safer. As discussed in the previous sections and provided in Tables 1, 2, and 3, all diabetes tablets have the potential to cause unfavorable effects – both minor and major.
- Metformin emerges as a superior drug based on the available evidence. This medication lowers HbA1c the exact same quantity or more than other diabetes drugs, does not cause weight gain, decreases low-density lipoprotein (LDL) cholesterol and triglycerides, and appears to have the safest profile when comparing serious side effects in individuals who do not have kidney, liver, or heart disease. As additional gone over listed below, nevertheless, specific patients should not take metformin.
- Taking two diabetes drugs can have a favorable additive affect on lowering HbA1c. This is a major plus for the lots of people with diabetes whose blood glucose is not well managed by a single drug. The downside is that taking two drugs postures a higher risk of side effects. If lower dosages of each drug are used in combination, the added risk of side effects typically can be minimized.
- The newer drugs are more expensive. The newer oral diabetes medications cost lot of times more than the older ones.
As pointed out previously, the diabetes drugs have clearly various “safety profiles.” This element may be the main driver of your and your doctor’s decision – for initial and on-going treatment.
For example, the evidence plainly shows that the sulfonylureas posture a greater risk of hypoglycemia than metformin or the thiazolidinediones (Avandia and Actos). Specifically, between 9 and 22 percent of individuals taking one of the sulfonylurea drugs can expect to have an episode of possibly dangerous low blood glucose, compared with absolutely no to 7 percent taking metformin.
The risk of hypoglycemia is about the same for the sulfonylureas and repaglinide (Prandin), but two recent research studies recommend that repaglinide may cause less hypoglycemia in senior citizens or in individuals who avoid meals.
As excellent as it searches in other methods, metformin has been associated with uncommon events of lactic acidosis – a develop of lactic acid in the blood that can be deadly. This uncommon risk appears to exist mainly for individuals with diabetes who also have kidney disease and/or heart failure. As a result, such patients ought to not be prescribed metformin.
Small however frustrating side effects might likewise play a role in your choice of a diabetes medication. For instance, intestinal side effects – including bloating, gas, queasiness, and diarrhea – are more frequent with metformin and also acarbose.
Among the newer classes of drugs postures an elevated risk of heart failure. Proof overwhelmingly shows that the thiazolidinediones – Avandia (more about this drug below) and Actos – pose a 1.5 to 2 times increased risk of heart disease compared to other diabetes medications. In between 1 and 3 people in 100 without a history of heart disease will establish the condition if they take among these drugs. In contrast, metformin and the sulfonylureas do not raise the risk of heart failure in any considerable method compared to the general risk of this condition among individuals with diabetes, which is greater than normal.
See also: Anti-Obesity Drugs: A New Approach
Due to the fact that of the clear evidence of heart failure risk, both Actos and Avandia carry a high-profile “black box” alerting about it on their labels (assistance to doctors and patients on how to use them). If you are taking one of these medicines and have swelling of any part of your body, sudden weight gain, or breathing problems, you must contact your doctor instantly.
Table 2. Effects of Oral Diabetes Drugs on Specific Measures
|A down arrow (▼) means a decrease or decline; an up arrow (▲) means increase; and a diamond (♦) 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 Hypo – glycemia (% of people)1||Average change in weight (lbs)|
|Glyburide||▼ 1.3-1.8||♦||♦||♦||▼ 10-20||10-22%||▲ 5-10|
|Glipizide||▼ 1.3-1.8||♦||♦||♦||▼ 10-20||10-15%||▲ 5-10|
|Glimepiride||▼ 1.3-1.8||♦||♦||♦||▼ 10-20||9-14%||▲ 5-10|
|Dipeptidyl peptidase IV inhibitor|
|Metformin + sulfonylurea (Glucovance)||▼1.7-2.3||IE||▼5-7||♦||▼20-40||14-28%||▲5-10|
|Metformin + rosiglitazone (Avandamet)||▼1.3-2.0||IE||▲12-15||▲3||♦||0-7%||▲5-10|
|Sulfonylurea + rosiglitazone (Avandaryl)||▼1.7-2.3||IE||▲10-12||▲3||♦||18-30%||▲5-10|
Key: lbs=pounds; mg/dl=milligrams per deciliter of blood; mmHg=millimeters mercury; HbA1c=hemoglobin A1c; LDL=low-density lipoprotein cholesterol; HDL= high-density lipoprotein cholesterol.
- 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.
- IE = insufficient evidence for this drug on this measure to reach any meaningful conclusions.
- Results based on one short-term study (<1 year).
- Results are based on data from a systematic review plus a large randomized study.
- Results are based on data from two studies.
Do not Take Avandia; Actos a Last Resort
In addition to heart failure, Avandia also increases the risk of heart attack and stroke. Because of that, the FDA has actually limited use of the medication (and combination items which contain it) just for people who have persistent high blood sugar levels after taking another medication and who can’t take an alternative such as Actos. Avandia and mix products, Avandamet and Avandaryl, are not readily available at drug stores. Instead, if you need one of those medications, both you and your doctor have to sign up with a special program to have them delivered by mail-order.
If you are already taking Avandia, Avandamet, or Avandaryl, and they are working to manage your blood sugar, you can continue to take them, but we highly suggest you talk about with your doctor whether they are proper for you.
Both Actos and Avandia have also been connected to a somewhat increased risk of fractures of the upper and lower limbs, such as the wrist or ankle, in women. The risk was little – about 2 percent higher in individuals taking Avandia or Actos compared to those taking other diabetes drugs, according to preliminary studies.
Actos increases the risk of bladder cancer in people who take it for a year or longer. The risk uses to all drugs containing pioglitazone, consisting of Actoplus Met, Actoplus Met XR, and Duetact. France banned Actos and combination pills due to the cancer risk.
Our medical consultants say that people with diabetes need to use Actos only as a last resort, which suggests just if all other choices have actually stopped working. People who have actually previously had or currently have bladder cancer ought to not use Actos or the mix tablets which contain it at all.
If you’re on Actos, ask your doctor if it’s truly needed and if you ought to switch to another drug, such as metformin either alone or in mix with glipizide or glimepiride. Also, look out for signs of bladder cancer, that include blood or red color in your urine, urgent have to urinate or pain while urinating, and pain in your back or lower abdominal areas. Contact your doctor if you experience any of those symptoms.
Actos has actually been greatly promoted to doctors and customers in the U.S. As a result, it might be over prescribed to individuals who would do just as well to take metformin and/or a sulfonylurea. Both Actos and Avandia (until just recently) have been marketed particularly to minorities too, but there is no excellent proof that any diabetes medicine is more reliable or safer in African-Americans, Hispanics, or American Indian patients than in other ethnic groups.
Our choices and recommendations
Taking effectiveness, safety, side effects, dosing, and cost into factor to consider, we have picked the following as Consumer Reports Best Buy Drugs if your doctor has chosen that you require medicine to control your diabetes:
Metformin and Metformin Sustained-Release – alone or with glipizide or glimepiride
Glipizide and Glipizide Sustained-Release – alone or with metformin
Glimepiride – alone or with metformin
All these medicines are available as affordable generics, either alone or in mix. In the last few years, a strong medical consensus has emerged in the U.S., Europe, and Australia that a lot of newly diagnosed individuals with diabetes who require a medicine needs to first be recommended metformin.
Based upon the systematic assessment of diabetes drugs that forms the basis of this report, we accept that suggestions. Unless your health status avoids it, attempt metformin first. If metformin fails to bring your blood glucose into normal variety, you might require a 2nd drug. Most frequently that need to be among the two other Best Buys we have actually picked.
If you are unable to take metformin or do not endure it well, you deal with an option of one of the sulfonylureas or a newer medication as your first line medicine. Regardless of the raised risk of hypoglycemia, we recommend attempting glipizide or glimepiride. If glipizide or glimepiride alone fail to bring your blood glucose into control and keep your HbA1c at or below 7 percent, your doctor will likely recommend a second drug.
If upon initial medical diagnosis your glucose and HbA1c are rather high, you may be recommended a combination of two drugs at the start of treatment – usually metformin plus a sulfonylurea.
Januvia and Onglyza – the newest oral diabetes drugs
Januvia and Onglyza are the first two drugs in a brand-new class of diabetes medications called dipeptidyl peptidase 4 inhibitors. No studies on these drugs have followed patients for more than two years, so their effectiveness and safety profiles are not plainly established yet. Neither Januvia nor Onglyza has been revealed to lower HbA1c as well as metformin or glipizide, so we do not advise them as first-line drugs. Another downside is that both are substantially more expensive than generic variations of other diabetes drugs.
Lastly, as a reminder, if your diabetes is not managed by pills, you may need to take insulin or one of the more recent drugs available by injection just.
Table 3. Advantages and Disadvantages of the Oral Diabetes Drugs
|The sulfonylureas (glyburide, glimepiride, glipizide)|
|The alpha-glucosidase inhibitors (acarbose, miglitol)|
|The thiazolidinediones (Actos, Avandia)|
|The meglitinides (nateglinide, repaglinide)|
|The DPP-inhibitors (Januvia, Onglyza)|