Blast It! Starting on Multiple Meds Makes Sense

Skimming through the latest edition of the diaTribe newsletter, my interest perked up when I read a report on the Banting Lecture by Dr. Ralph DeFronzo of the University of Texas Health Science Center and recipient of the 2008 Banting Medal for Scientific Achievement. In particular, his criticism of the American Diabetes Association’s treatment guidelines, “which recommend lifestyle changes and metformin as initial therapy for Type 2 diabetes,” jumped out at me.


He recommends instead beginning with a triad of drugs: metformin (brand name Glucophage and others), exenatide (Byetta), and a thiazolidinedione, or TZD, such as pioglitazone (Actos) or rosiglitazone (Avandia).

“Dr. DeFronzo’s rationale for multiple drug therapy,” the article says, “was to simultaneously treat the multiple organ dysfunctions that contribute to diabetes and at the same time protect surviving beta cells, and possibly augment them.”

It’s a method that endocrinologist Allen B. King, cofounder and director of the Diabetes Care Center in Salinas, California, has used for years. He calls it “Blast and Taper Fast.” I’ve been to his clinic a couple of times to get my basal doses tweaked. It’s an awesome place.

At the time I talked to Dr. King about Blast and Taper Fast, Byetta, which basically helps your body produce the right amount of insulin at the right time, was not yet on the market. Depending on an individual’s fasting blood glucose levels, Dr. King “blasted” him with up to three drugs: a TZD, which improves the body’s insulin sensitivity; metformin, which adds insulin-sensitizing and glucose-lowering properties to the mix, and a sulfonylurea to stimulate the pancreas to release more insulin.

As you can see, Dr. DeFronzo has substituted Byetta for Dr. King’s sulfonylurea.

I wish I could have talked to Dr. King to get some follow-up information, but the Fourth of July holiday weekend and my impending departure for Camp Lobegon put the kibosh on that.

Still, the idea itself of “blasting” high blood glucose levels with a combination of drugs is, in my opinion, very superior to the “step-up” method: starting with one drug, raising the dose, adding something else, raising the dose of that one, and on and on.

It’s psychological.

“I’m a failure!” the latter method screams. “I can’t take care of my diabetes! The doctor gave my medicine, and I STILL can’t get my BGs down!”

Of course, many doctors fail to explain that, by the time you’re diagnosed with Type 2 diabetes, up to 80 percent of your beta cells may already be kaput. They also fail to explain that more beta cells will fail over time and you’ll need more medicines, or even insulin, to help you manage your diabetes.

There you are: Your blood glucose is high, you’ve just been diagnosed with Type 2 diabetes, and you get one drug that brings your levels down…just a little bit.

So your doctor ups the dose. Meanwhile, in many cases, admonishing you for being “noncompliant.” “You’re not following your diet,” Doc says. “You’re not exercising. If you don’t get that weight off and get your sugar down, I’m going to have to put you on insulin.”

In reality, you aren’t getting the right kind of—or enough—medicine.

How much better is it to start you out with a variety of drugs that target different areas and to reduce the doses or take them away as your blood glucose levels decrease?

“Yay! I’m doing great! The doctor is reducing my doses! I don’t have to take X drug any more!” the “Taper Fast” part says.

Besides, Dr. King says, it takes more medicine (or insulin) to bring down a high blood glucose level than it does to maintain optimal glucose levels. In addition, people are more likely to check their blood glucose in the beginning. Seeing improvement in blood glucose levels beats getting constantly high numbers any time. It might even compel you to continue to check your glucose.

Also, with a doctor who “gets it” and who has explained the pathology of Type 2 diabetes, you might even be willing to say, “My numbers have been going up; I think it’s time for a change in medicines.”

That change may include dropping some medicines and adding insulin. It’s not a bad thing: It just means that you need to supplement a hormone that your body doesn’t make enough of. In addition to taking insulin, I also take metformin to help nullify some of my insulin resistance.

Type 2 diabetes is a multifaceted condition. It takes more than one method to help you manage it. Personally, I like Drs. DeFronzo and King’s multidrug technique much better than the ADA’s. Physically and psychologically, it makes much better sense.

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  • Ephrenia

    While what these Drs are saying sounds logical based on the knowledge of how diabetes works, I still have a concern about starting multiple meds at the same time. Mainly, side effects. If you begin multiple medications together and experience side effects, how do you know which med is causing the side effects?

    Perhaps Doctors in general just need to look more closely at how they portray the need to add more meds. Your scenario of “I’ll have to punish you with insulin (paraphrased)” is all too common and SHOULD NEVER be heard by a patient. Drs should explain diabetes as a degenerative disease and tell patients to expect increases in meds.

    Personally, I wish CDEs could use a degree in Education as a jump off toward certification. I’d have already begun the training!

  • CalgaryDiabetic

    Dear Jan.

    You would think that insulin and more insulin would be the answer. Not so. With more insulin I become uncontrollably hungry and eat more causing the insulin to stop working. Of course you can up the insulin dosage but you will end up weighting 500 lb or have a coronary whichever comes first. So I tried something new. I keep on taking my 45 units of Lantus every 30 hours ( yes, in my case it works for 30 hours in some people only 18 hours) and I stopped using all Novorapid. Instead I am trying 500 mg of Metformin 4 times per day only in addition to the Lantus. By some miracle all hunger has vanished and the blood sugar spot checks are not quite as good but still reasonable. Well if this works and I am able to loose 10 lb, I will reconsider my firm belief in tight control (i.e. HA1C below 6.5%). The only problem is Metformin makes me extremely tired. God does not make it easy for Diabetics but maybe this still beats cancer. And of course eating less than 20 grams of carbs per meal is useful. Preferably veggies and fruits and minimal grain products. Diabetes care may be an experimental science so it is good to have a Doctor that is not carved in stone and is open to new and varied ideas.

  • Colorado Springs

    I’m very concerned about more meds with corresponding side effects. But that is the typical Medical Model. It makes sense, but thank you, no. I’m on 2, 500 mg Metformin daily. My A1C (Type 2)varies from 5 to 6.65. I eat fruits and vegetables and work out at Curves as often as I can (never less than 15 to 16 times a month). I also get every other week Chriopractic adjustments. This is working for me, as a very active & busy retiree.

  • Joe

    I’m not so concerned about multiple meds. I’m on plenty, but I balk at the recommendation of putting *anyone* on Actos. Bladder cancer is a horrible way to die.

  • jim snell

    While it may make sense to take the blunderbuss
    open choke approach to diabetes; the present (mis)understanding about what is really going on in type 2 diabetes is a frightening prospect. In the end, tuning and getting a multiorgan – hormone system back to functioning properly will in fact take a range of drugs and and approaches.

    That said my beef is simply this:

    a) type 2 is not type 1 and did not arrive at that point as a type 1 does and applying type one stratagies ( just add more insulin) has been a monsterous failure – look at the numbers. and increases world wide. In any other company we would fire the chief executive and his entourage and get a new team.

    b) while as one ages and the longer a type 2 keeps saturating his body with excess glucose, why yes he may need some more insulin – but that is not the fix.

    c) glucose flow control in the skeletal muscles is not properly understood and present knowledge seems to walk off with the view that the fat cells and skeletal muscles are infinit energy dumps for liquid glucose – if only we could add enough insulin. (NOT)

    d) Now that metformin has been fully reserached and now understood that it stops excess glucose release from liver; notwithstanding all the experts stamping their feet that there is no such thing as a liver leak. Really? Metformin has become the most widley and popular drug used in type 2 diabetes and since it helps stop excessive liver glucose release helps type 1’s as well.

    e) stratagies like bariatric surgery and extreme diets show that yanking back on the excess glucose input to the type 2 system is showing amazing chnages and hopes thanks to non invasive MRI spectography pionered as well as used at University of Newcastle upon Tine.

    f) recovery of type 2 islets in a type 2 pancreas have been shown when the excessive oxidative stress and excess glucose stress is removed. The islets are not dead.

    g) from my experience actos has been proven to be helpful when needs to stuff more glucose in the skeletal muscle cells after those cells refuse to load in anymore under insulin control.

    In the end, the multiple drug strategy may be appropriate when we properly understand what the body is doing and how it misfires. My current data says we are still standing in a dead end mine tunnel with the lights turned off.

    That aside, my thanks and blessings to all those investigating and experimenting with these stratagies to learn as much as possible and hopefully arrive at an answer.

    I believe it was Roosevelt who was quoted as saying in the depth of the 1929 great recession that we may not know what we are doing or have good answers but we will keep trying ideas till we find those answers that work.

  • Rosemary

    I agree with the metformin and Byetta. However, I am very anti-Avandia/Actos. I experienced every negative side effect of Avandia some years ago. Granted my A1C was 5.5 (the Dr thought it was working wonderfully, however, I experienced such SOB I couldn’t walk up stairs or to the mailbox, and I failed a stress test miserably. Even went so far as an angiogram, with no blockage. Ankles and feet were very swollen. I was in the research group for Byetta and think it is wonderful. Between Byetta 10 mcg 2x per day, and 500 mg Metformin (generic) 3x per day, my A1C runs 6.0. My exercise is moderate – in the pool every day, WII bowling, some walking. Have had type 2 for 20 days. Avoid bread, white flour products, pasta. Eat plenty of fruit, veggies, meat, some cheese, and nuts.

  • BK CDE

    I like the idea of get good control quickly and then back off if you need to. In the US we tend to start slowly and take too long to add treatments. Sorry to say, but that is mostly the fault of prescribers. Granted sometimes it is the patient bargaining to just try another 3 or 6 months, but sometimes the patient is ready and the doctor wants to wait when they should be advancing the treatment.

    My understanding is that in Europe it is more common to start with meal time insulin than basal. Some also advocate starting right out with insulin for type 2 and then getting off it once control is achieved. I can see an advantage to that also. Feel better quicker, lose the stigma around insulin right away even if you only need to use it for a couple weeks in the beginning, and probably use less of the other meds when you transition to them after getting control with the insulin.

    Again, a great article.

  • jim snell

    excellent comments. I did not point out about avandia/actos as my kidney Doctor wanted me off that stuff as my kidneys were heading south. I did and got numbers down and now kidneys stable and behaving thelselves. Not to disrupt my earlier response; I left that part out.

    As a 30year+ type 2 now on insulin, I also wish I had gone on insulin early/originally rather than the other pills glyburide, gimperide,starlex et all.

    Metformin has been a life saviour stopping excess liver glucose release.

    Thank you for all the excellent other comments and Jan Chait jumping on this key point!