A New Paradigm for Dosing Diabetes Drugs in Type 2 Diabetes?

Which is better, adding medications one at a time or all at once? It’s a question physicians will be pondering as they discuss the results of an ongoing study into how to dose oral medications for people with type 2 diabetes.

As we know, diabetes is a progressive disease with glucose control worsening over time due to loss of beta cell function, so figuring out the best way to maintain what beta cell function remains is a key to successfully treating the disease. (The loss of metabolic control in diabetes is also associated with functional aberrations in the pancreas, the liver, the muscle cells, the gastrointestinal tract and the brain.)

The traditional thought has been to add medications in a step-wise fashion when the A1C starts to creep up on the current medication regimen. For example, a person with type 2 diabetes may start by taking metformin, adding a sulfonylureas or a thioglitozone then an incretin such as Victoza® or Bydureon®. Finally insulin is introduced. But this method has a built-in disadvantage. Patients who are ready for the next step have blood glucose levels above the target range.

So Muhammad A. Abdul-Ghani, M.D. and colleagues, researchers at the Texas Health Science Center in San Antonio, Texas, decided to look at the problem in a different way. They hypothesized that attacking the glucose control problem from more than one angle at once would allow for better, more long-lasting results.

The study compared the use of triple therapy treatment to conventional step-wise therapy in 155 participants. All the subjects were obese and newly diagnosed with diabetes. They started the trials with a mean A1C of 8.6 percent. One group was given triple therapy starting with 1000 mg/day of metformin, 15 mg/day of pioglitazone, and 5 µg twice daily of exenatide. The drugs were increased as needed to a maximum of 2000 mg of metformin, 30 mg of pioglitazone , and 10 µg of exenatide. The conventional group received metformin at 1000 mg increasing to its maximum dose of 2000 per day. Glyburide and finally insulin were added if the fasting blood glucose exceeded 100mg/dl.

The results Dr. Abdul-Ghani presented were interim (the study has another year to go) but the data looks promising. The goal was to keep the A1C under 6.5 percent. Failure of treatment in either arm of the study was an A1C of 6.5 percent on two consecutive clinic visits.

Although participants in both treatment arms were able to keep glucose in control, the participants receiving triple therapy did significantly better. They were able to maintain a lower A1C at the two year mark than those using conventional therapy and with less hypoglycemia. In addition, those on the triple therapy achieved a small amount of weight loss, while participants taking the conventional approach gained weight.

The study is small and some researchers found the use of glyburide as one of the drugs in the conventional arm inappropriate (glyburide is associated with more frequent hypoglycemia). And certainly more studies need to be done before doctors throw out a tried-and-true paradigm. However, this study does offer hope that it is possible to slow down the inexorable decline of beta cell function.

The results of the study were presented by Muhammad A. Abdul-Ghani, MD, from the University of Texas Health Science Center at San Antonio at the American Diabetes Association 2013 meeting.


  1. “As we know, diabetes is a progressive disease with glucose control worsening over time due to loss of beta cell function…”

    Actually, do “we know” this? There a growing body of evidence – early stage, but it IS there – that “lifestyle” T2D may NOT be, inevitably, “a progressive disease”. Until such fundamental questions are answered and major empirical studies are now underway or soon will be, everyone should take a step back from the sensationalist panic button!

    And, NO, I’m not saying that T2D is not a serious condition, the truth is, it’s still a condition much is to be learned about.

    Finally, surely our focus should be on 21stC solutions, not just more and more and more of the “diabetes” doom and gloom! It’s time for, everyone, to really start to look at the amount of research dollars, often over multiple generations, that have been poured into this field and who is producing what in the way of – Real Outcomes, as opposed to merely marginal improvements, to long ago established non-resolution based treatments!

  2. I think it’s so great that Muhammad A. Abdul-Ghani, M.D. and colleagues are asking this question! My dad used to say, “There is more than one way to skin a cat– but there is always a BEST way!” Type 2 diabetes poses a threat to many individuals, so it’s inspiring that this type of research is being done for them. It seems that this new strategy, without the “built-in disadvantage” is very promising. Thanks so much for sharing!

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