Friday, May 27, 2016

Perspective and common sense in managing type 2 diabetes in older individuals

A recent JAMA paper reviewed this topic. From the abstract:

Four large randomized clinical trials (RCTs), ranging in size from 1791 to 11 440 patients, provide the majority of the evidence used to guide diabetes therapy. Most RCTs of intensive vs standard glycemic control excluded adults older than 80 years, used surrogate end points to evaluate microvascular outcomes and provided limited data on which subgroups are most likely to benefit or be harmed by specific therapies. Available data from randomized clinical trials suggest that intensive glycemic control does not reduce major macrovascular events in older adults for at least 10 years. Furthermore, intensive glycemic control does not lead to improved patient-centered microvascular outcomes for at least 8 years.

The surrogate endpoints for microvascular disease are things like findings of retinopathy or laboratory evidence of renal involvement. This was the basis for a shrill body of opinion following the release of the UKPDS findings that intensive glycemic control in DM 2 was not effective because the improved endpoints were not “outcomes that mattered” (eg blindness or ESRD resulting in the need for chronic dialysis). I've come to consider statements like that as anti-EBM because under first EBM principles it is the patient who decides what outcomes matter, not someone else from afar. As the JAMA paper authors acknowledge, the surrogate nature of the outcomes lasts about 8 years. Longer term follow up of the UKPDS suggested differences in more robust clinical endpoints. In patient-centered decision making a lot depends on the patient's expected longevity.

The paper goes on:

Data from randomized clinical trials consistently suggest that intensive glycemic control immediately increases the risk of severe hypoglycemia 1.5- to 3-fold. Based on these data and observational studies, for the majority of adults older than 65 years, the harms associated with a hemoglobin A1c (HbA1c) target lower than 7.5% or higher than 9% are likely to outweigh the benefits.

So according to these authors the optimal range for many patients in an internist's practice is an A1c level between 7.5 and 9. That bold statement runs counter to a lot of prevailing diabetes dogma. But the harm associated with intensive glycemic control is more than hypoglycemia. For although intensive control does without question confer microvascular benefit, it also seems to result (with a few particular exceptions) in macrovascular harm. See here.

More from the article:

However, the optimal target depends on patient factors, medications used to reach the target, life expectancy, and patient preferences about treatment. If only medications with low treatment burden and hypoglycemia risk (such as metformin) are required, a lower HbA1c target may be appropriate.

Again, it goes beyond hypoglycemia. Metformin is one of only two diabetes drugs found to confer macrovascular benefit and it is likely a pleiotropic effect, having little if anything to do with blood sugar. It would also be reasonable to say that nonpharmacologic modalities (diet, exercise) would confer benefits across the range of A1c.

The article concludes:

High-quality evidence about glycemic treatment in older adults is lacking. Optimal decisions need to be made collaboratively with patients, incorporating the likelihood of benefits and harms and patient preferences about treatment and treatment burden. For the majority of older adults, an HbA1c target between 7.5% and 9% will maximize benefits and minimize harms.

In discussions of diabetes we have, ever since DCCT and the advent of home glucometers and A1c, developed an obsession with glucose lowering. Diabetes, however, is multifaceted and there is much more to consider. Despite a few omissions, all in all this paper is a great discussion of the treatment of type 2 diabetes in accordance with the principles of evidence based medicine.

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