Type 2 Diabetes Drugs – Results of Recent Study

We know that diet and exercise can prevent the onset of type 2 diabetes in people with impaired glucose tolerance. We also know that healthy lifestyle measures are more effective than even the most effective drugs. That being said, we also know that in the real world with Mickey Ds and Starbucks on every corner, long work hours, longer hours in front of the computer, and way too few hours exercising our body parts, that medications will be a part of the treatment armamentarium utilized to prevent type 2 diabetes.

So the question before us today is which drug should be used. An editorial in the March 20, 2007 issue of the Annals of Internal Medicine takes a stab at answering that question.

David Nathan, MD from the Massachusetts General Hospital Diabetes Unit and Michael Berkwits, MD, Deputy Editor of the Annals review the results of the DREAM trial (AKA, the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication trial — seems like you can’t have an important trial nowadays without a cute acronym).

The DREAM trial randomly assigned more than 5,000 patients with impaired fasting glucose (>110 mg/dL, but less than 126 mg/dL) or impaired glucose tolerance (a glucose level 2 hours after an oral glucose load between 140 mg/dL and 199 mg/dL) into one of four groups. One group received ramipril (an ACE inhibitor), one received rosiglitazone (an insulin sensitizer), one group received both drugs, and one group received a placebo.

The participants were evaluated after 2, 6, and 12 months and annually thereafter to determine if they had either developed diabetes or died. They were also evaluated to see if their glucose levels improved during those time frames. The participants were middle-aged and they were obese (mean BMI 31 kg/m2).

Here is what the study showed:

  • Participants taking the drugs had a significant reduction in the progression to type 2 diabetes
  • The reduction was entirely attributable to taking rosiglitazone.
  • More patients taking rosiglitazone regressed to normal blood glucose levels (almost 39% in the rosi group compared to 20% in the placebo group.
  • Although both medications were generally safe, rosiglitazone was associated with a higher prevalence of peripheral edema (swollen ankles) and a ~ 2.2 kg weight gain. In addition, there was an increased frequency of heart failure in a small number of patients (0.5% in the rosi group compared to 0.1% in the placebo group)

The authors talk about what clinicians (and patients) should do in light of this new information. First of all, they point out that rosiglitazone is expensive and has some uncommon but serious side effects. There are, they remind us, other medications that have been shown to prevent progression from impaired glucose tolerance to type 2 diabetes.

Metformin is available as an inexpensive generic formulation. At least in people with BMIs of 35 or higher, the percent reduction in progression to diabetes is only slightly lower than that described with rosiglitazone (53% vs. 60%). In addition, it is well tolerated except for some minor gastrointestinal symptoms, and it is much cheaper. The other effective drug, acarbose, is poorly tolerated because of adverse GI side effects.

So what’s a clinician to do?

  • Continue to counsel and support patients with impaired glucose tolerance or impaired fasting glucose to adhere to a healthy lifestyle (you know, diet and exercise).
  • For patients unable to unwilling to make these changes, they recommend considering metformin, as opposed to rosiglitazone, as a medication to prevent type 2 diabetes.

It is noteworthy, that Dr. Nathan lists GlaxoSmithKline, makers of Avandia, the brand name for rosiglitazone, as a potential financial conflict of interest. His recommendation to not go with rosi as a first line diabetes prevention drug must surely have caused some heartburn in GSK marketing circles.

Type 2 Diabetes – Using Your Diabetes Medications Safely and Effectively

There are many different medications available to help manage your blood sugar levels. But, like all medications, they are more effective and safer when they’re used correctly. This means taking them at the right time and taking the right dose. Here is some information to help you use your medications correctly and get the most out of them. First, it’s helpful to understand the different classes of diabetes medications and how and why each type is effective…

1. Alpha-glucosidase inhibitors make it so your body doesn’t break down carbohydrates, or breaks them down more slowly. They are starch blockers. The two medications in this group are Precose and Glyset and need to be taken with every meal.

2. Bile Acid Sequestrants (BAS). Welchol and Questrant fall into this group and are often prescribed to lower cholesterol levels and are also effective in lowering blood sugar levels.

3. Biguanides – metformin (Glucophage, Glucophage XR, Fortamet) limit how much glucose your liver produces. Metformin puts a clamp on your liver and prevents it from dumping out too much sugar. Metformin has become the drug of choice for people with Type 2 diabetes since its introduction in 1994.

4. DPP-4 Inhibitors or Insulin Extenders help lower blood sugar levels by extending the action of insulin. They include Januvia, Onglyza, Tradjenta, and Nesina.

5. Sulfonylureas, which include Glucotrol, Glucotrol XL, Micronase, Glynase, Diabeta, and Amaryl, stimulate the cells of your pancreas to produce more of its own natural insulin.

6. Meglitinides blunt the normal spike in blood sugar that occurs after eating. They enter and leave your body quickly. They are taken 5 to 30 minutes before eating, and stop working within hours. Medications include repaglinide (Prandin) and nateglinide (Starlix).

7. SGLT2 Inhibitors include canagliflozin (Invokana) and dapagliflozin (Farxiga). They help your kidneys reabsorb glucose.

8. Thiazolidinediones are usually used together with other medications and include rosiglitazone (Avandia) and pioglitazone (Actos). These drugs help make better use of the insulin you have and tells your liver not to release any of its stored glucose.

It’s important to take your diabetes medications at the prescribed time and at the prescribed dose to get the desired effect on your body. Many of these medications need to be timed with your meals. For example, sulfonylureas need to be taken before meals so they can produce insulin to help you use the carbohydrates in the meal. Biguanides should also be taken with food. This helps avoid side effects like diarrhea, upset stomach, and cramps.

Taking the right dose of your medications is important too. Some medications are designed to be started at a lower dosage and gradually increased based on how your body responds. Others need to be matched to your meals, so if you miss a meal you should also skip a dose of the medication. And still, other medications are taken in an exact dosage every time. With all the different dosing directions, talk to your doctor or pharmacist and make sure you understand the directions.

It’s also important to remember taking medications for Type 2 diabetes doesn’t address the root cause of the problem. By eating a healthy diet, exercising, and losing weight, you may be able to manage your diabetes without medications and even reverse the disease.

Type 2 Diabetes Patients Alert

Type 2 diabetes is the focus of a study that says a prediabetes and a patient with the same condition receiving rosiglitazone or pioglitazone is more liable to have CHF or congestive heart failure. However, it said further that the risk for CVD or cardiovascular death is not increased.

The importance of this I believe is in making treatment decisions based on the results that are most relevant to the patient. The outcome we are talking about here are the vascular complications and the quality and quantity of life instead of just focusing simply on sugar glucose control.

A team at Lahey Clinic Centre led by Dr. Richard Nesto analyzed seven trials involving 20,191 patients of drug related CHF in patients with prediabetes and type 2 diabetes who had been given rosiglitazone or pioglitazone. They measured the development of CHF and CVD in these patients.

The researchers found 72% increase in CHF but this was noted among different backgrounds of patients: those with prediabetes, those with no cardiovascular disease with type 2 diabetes, those with the same conditions for both, and those with documented CHF and type2 diabetes.

The scientists said the CHF risk was wide-ranging among the groups. This should guide the doctors in selecting appropriate patients when describing these drugs. So despite the fact that these drugs lower the glucose, they should not be prescribed for those who have heart failure.

They should also be prescribed for glycemic control with care for those who do not have heart failure but with cardiovascular disease. For those without cardiovascular disease and type 2 patients who have lower risk for CHF, the use of the drugs should still be considered against the benefits and risks of the other medications.

Let’s hope they succeed in this endeavor as it will make life so much easier for the diabetics. Let’s also hope that they take time in putting this in the market and wait for all the bugs to be ironed out before releasing this product to the public.

The researchers admitted that they didn’t have enough follow-up to determine the link between the drugs and the CDF and CVD. They also need more data to differentiate the effects between the two drugs and to determine whether CHF is a harmful effect or an endpoint.

The jury is still out but the researchers are continuing their search for better and newer drugs. They are hoping for new ones that will help control the blood glucose. An example is Troglitazone which is a relatively new oral hypoglycemic agent. This is supposed to decrease not only the fasting blood glucose but also the one taken after meals.

Troglitazone is also known to improve the glucose tolerance and to increase insulin sensitivity. So far it has results that are encouraging for type 2 diabetes patients. This drug belongs to the class of drugs known as thiazolidinediones.

So you see despite some bumps in the road as shown in the study that patients taking rosiglitazone or pioglitazone are more liable to have CHF or congestive heart failure, there’s still hope for the future. Despite the barriers that need to be overcome, the promise of a cure is on the horizon.