Oral Medication for Type 2 Diabetics

Many readers will be familiar with the NHS protocol for glycaemic control in Type 2 Diabetic adults. Basically, it consists of an iterative series of HbA1c tests. If HbA1c < NICE target figure, the patient ‘reverts to routine monitoring for expected deterioration’. If the HbA1c >= NICE target figure, the patient is reviewed for lifestyle intervention and placed on some oral diabetes medication. Depending on where in the iterative testing series the patient is, the medication may be a single drug, double drug, triple drug regimen or in extreme cases an insulin regimen.

Concern over the withdrawal of Actos and Avandia over safety concerns led me to consider what was known regarding the benefits and harm of oral medication for Type 2 diabetic adults.

The evaluation of oral medication for Type 2 diabetics is difficult because there are so many classes of drugs and many individual drugs within each class. Given that much of the drug information mainly comes from industry-sponsored clinical trials, there is a clear need for a systematic, objective analysis of the evidence.

Fortunately, the U.S. Congress directed the AHRQ to establish the Effective Health Care Program to conduct and support research with a focus on “outcomes, comparative clinical effectiveness, and appropriateness of health care items and services (including prescription drugs)”.

The resulting analysis of 216 studies of oral medication for Type 2 diabetics was reported in Ref 1. A follow up analysis was reported in Ref 2.

These reports are important for several reasons. No systematic review had previously summarised all available placebo-controlled trials and head-to-head trials that considered effects on HbA1c values, lipid levels, and body weight as well as other clinically important outcomes, such as adverse effects and macro-vascular events. The reports should move researchers away from industry-sponsored single studies that are often carefully designed to increase the probability of a result in favour of the drug manufacturer – the interested reader no longer has to worry about commercially biased conclusions.

The authors drew the following conclusions.

1.      Older drugs (metformin, second-generation sulfonylureas) have similar or better effects on glycaemic control, lipids, and other intermediate end points, than newer, more expensive drugs (thiazolidinediones, α-glucosidase inhibitors, and meglitinides).

2.      The drug effects on major clinical end points, such as cardiovascular mortality, were inconclusive.

3.      Metformin is recommended as an initial drug therapy because it has the best balance of efficacy, side effects and cost.

The reports have their limitations. They only briefly address the class of dipeptidyl peptidase-IV inhibitors and do not highlight the relative ineffectiveness of triple oral medication therapy, as reported in Ref 3

After spending some time reading the report, my position is as follows. Because type 2 diabetes is a progressive disease caused by β-cell failure, some of us will eventually need to move along the iterative sequence from single drug regimen, to double drug regimen, to … , to insulin. Given that safety data regarding the long-term safety of older oral medications for Type 2 diabetics is sparse, it seems reasonable when considering newer drugs whose long-term safety is even more unknown, to be cautious in using them in lieu of the long-established drugs.

Of course, on this forum, there is little need to discuss the advantages of low carbing in the iterative sequence of testing. Suffice to say – low carbing – lower medication.

1:  http://www.annals.org/content/147/6/386.full

2:  http://www.annals.org/content/early/2011/03/11/0003-4819-154-9-201105030-00336.long

3:

http://care.diabetesjournals.org/content/29/6/1395.full?ijkey=78f874828b720878f9b2c36a0c92282921591ef7&keytype2=tf_ipsecsha

John