Should Antidiabetic Agents Be Prescribed at the Prediabetic Stage?

Boris Hansel, MD


June 04, 2015

Today I'd like to talk about prediabetes and its treatment.But first of all, what is prediabetes? A person is said to be prediabetic if he/she has a blood glucose abnormality indicating a risk of becoming diabetic:

  • A fasting blood glucose level greater than 110 mg/dL (the cutoff is set at 100 mg/dL by the American Diabetes Association [ADA], up to 125 mg/dL); or

  • A 2-hour blood glucose level greater than 140 mg/dL (up to 199 mg/dL) during an oral glucose tolerance test, in which case one speaks of glucose intolerance.

Prediabetes is not a new illness that was created so that more and more expensive drugs could be prescribed. On the contrary, it's a concept used to prevent diabetes and, consequently, to avoid its complex treatment and its complications.

Approximately 70% of prediabetic patients will develop diabetes in the more or less long term, but because not all of them will, the term "prediabetes" has been criticized. However, the advantage of this term, or rather this concept, is to be able to engage patients at risk of developing the disease in a discussion early on and, as a result, to raise their awareness and initiate a prevention process. In this regard, what is most effective in reducing the risk for diabetes in prediabetics are lifestyle and dietary measures. In fact, it has been eminently shown that the risk for type 2 diabetes in prediabetics can be reduced by nearly 60%, a finding of a number of randomized trials.[1,2] The objectives can be stated in fairly simple terms: reduce weight by about 7% and engage in moderately intense endurance-type physical exercise for at least 150 minutes a week.[3]

Should We Prescribe Antidiabetic Medication?

The issue that arises is: What should be done in patients who do not adhere to these recommendations? Should antidiabetic treatment be prescribed at the prediabetic stage?

Metformin, like orlistat and alpha-glucosidase inhibitors, as well as the glitazones (which are no longer prescribed or marketed [in France]), and, more recently, glucagon-like peptide-1 (GLP-1) agonists, in particular exenatide and liraglutide, have been shown to be effective in preventing diabetes. Of all of these drugs, metformin is the one with the most favorable risk-benefit ratio, and it is the least expensive. This is why the ADA has, since 2008, been recommending metformin for prediabetic patients—in particular, those under the age of 60 years or whose body mass index is greater than 35 kg/m2 or who have a personal history of gestational diabetes.[4] Paradoxically, the US Food and Drug Administration (FDA) has never approved metformin for the indication of prediabetes, and there's little chance that they will. This is because the pharmaceutical companies that developed this drug would have to make a submission, and this would probably be too expensive and unprofitable for them, given the low cost of metformin, which is now manufactured generically.

In other countries, such as France, the 2014 type 2 diabetes screening and prevention guidelines make no mention at all of metformin for preventing diabetes.

So, in our practice, what should we do when faced with a prediabetic patient?

  • First, it's imperative that we talk to the patient about their prediabetes as soon as their fasting blood glucose level exceeds 100 mg/dL. This will serve to point out something concrete—namely, that they are at risk of becoming diabetic—and will provide an opportunity to initiate diabetes awareness. We can also calculate a diabetes risk score.

  • Next, we should initiate lifestyle and dietary measures as soon as possible, again, with the objective of preventing the onset of diabetes.

  • As for metformin, based on the ADA guidelines, we could prescribe it as soon as lifestyle and dietary measures fail, especially if the patient is at very high risk of becoming diabetic based on the scores. However, in the United States, prescribing metformin to prediabetics is still rare, as shown by a recently published study. In France, it's practically never done, which stands to reason, as there is no marketing authorization for metformin and there have never been any French guidelines for prescribing it [for this indication].

Therefore, for now, emphasis really needs to be placed on screening and risk awareness. As for metformin, it's a personal decision for physicians, but they should be aware that prescribing it is off-label because this use has not been approved [by the FDA].

Editor's Note: This commentary is an edited transcript of a video presentation published on Medscape France on May 22, 2015.


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