Avandia and exercise

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If you are taking Avandia or Actos and you have been reading about heart disease you may be concerned and you should be. As a class, these drugs increase your risk of heart disease and recent studies are confirming what we already suspected: Avandia is a bit worse on the heart than Actos.

However, there is something you can do to protect yourself. It seems that exercise does a very good job of reversing the problems caused by Avandia. I came across this clinical study last week and I wanted to share it with you.

The 1 year study was performed by a team of Greek doctors headed by Dr. Nikolaos Kadoglou and was published in the journal: Metabolism in November 2009. They chose 100 people in their late 50s or early 60s with type 2 diabetes who had not achieved good glycemic control with the combination of gliclazide (a sulfonylurea drug) and metformin. They were all overweight but were not taking any lipid lowering drugs and did not have any vascular complications. These patients were divided into 4 groups. The control group (we’ll call them the CO group) kept on as before. The next group received rosiglitazone (Avandia) in addition to their current therapy (let’s call them the RSG group). Group 3 exercised in addition to keeping up their original therapy (the EX group). Finally, the last group added both Avandia and exercise to their original therapy (the RSG+EX group). All patients were carefully examined before the start of the study to establish their fitness level as well as their lipid profiles, glycemic index, level of insulin resistance, and many other parameters. They were measured again after 1 year to provide the results of the study.

The exercise regimen started with a standard 45 min to 1 hour aerobic fitness class run at a local fitness center. The intensity of the exercise was tailored for each patient so that they were not in danger of hurting themselves or being asked to perform at an impossible level. Indeed the authors made the point that the exercise level began quite low and only slowly increased until individuals could achieve a reasonable level of effort (officially, 50% of VO2 peak). After the first month the exercise was further tailored to the individual with some running and some walking or using an exercise bicycle. After 8 months, the patients were on their own with individual exercise programs and simply checked in periodically so that the researchers could see how they were doing. Out of the 100 patients, 11 dropped out of the study for a variety of reasons, none of which involved dislike of the exercise.

The results were quite impressive. Nobody lost weight but then we already know that weight loss cannot be achieved by exercise alone unless we are talking enormous amounts such as a multiday mountaineering expedition – not exactly the sort of thing you plan on doing any time soon. Glycemic control, as measured by the amount of glycosylated hemoglobin, was about 0.5% higher in the CO group. In the EX group it dropped 0.3%. In the RSG group it dropped 0.8% and in the RSG+EX group it dropped 1.4%.

Lipid profiles also responded favorably with exercise. As seen in other studies Avandia treatment (the RSG group) resulted in an increase in total and LDL cholesterol. For the groups that exercised, however, HDL levels (the good lipids) increased while LDL levels and cholesterol (the bad lipids) decreased. Also, various other measures of lipids that are somewhat more specialized such as ApoA and ApoB1 showed improvement but only in the groups that exercised. Measures of inflammation (inflammation increases insulin resistance) also showed marked improvements both with exercise and with Avandia. The combination of Avandia plus exercise markedly improved this parameter.

Another issue that increases the risk of a cardiac event is fluid retention. Increased fluid causes an increased workload for the heart and Avandia has effects on the kidney that increases fluid retention. This was seen in the current study. The CO group showed no significant change in body water content while the RSG group experienced a significant change of 2.4% (+/- 1.4%). When Avandia was combined with exercise (the RSG+EX group) the number dropped to 1.6% (+/- 1.2%) and was no longer statistically significant.

Blood pressure, another measure that is associated with increased cardiac risk, was increased in the CO group and decreased in the EX, RSG, and RSG+EX groups.

Perhaps the most interesting and surprising result from the study was that Avandia alone improved VO2 max. This is a measure of aerobic capacity. Improving VO2 max is the Holy Grail for anyone who is involved in a sport that involves lots of movement. Fly fishing probably doesn’t get easier but tennis or basketball or soccer certainly does. The RSG+EX group saw a synergistic improvement in VO2 max which was much greater than the EX group.

So to sum up, the exercise groups performed about 2.5 to 3 hours of exercise a week for a year. They experienced marked improvements in insulin resistance, fasting glucose levels, lipid profiles and blood pressure. Avandia provided the expected improvements in glycemic control with the equally expected increases in fluid retention and cholesterol associated with increased cardiac risk. Exercise markedly reduced these cardiac risk factors while synergizing with exercise to improve glycemic control. Remarkably, Avandia actually improved the capacity of the study group making them more fit and capable of greater improvements in fitness.

Here are some questions. How much exercise do you need to do to achieve these benefits? Does Actos have the same properties or is this unique to Avandia? As usual, we end with the researchers’ mantra – “more work is necessary to unravel these important issues”. In the meantime, it wouldn’t hurt to go take a walk today.

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Jessica Apple

Fascinating post… and again we see how important it is to exercise.  I am very curious to know whether an Actos study would have similar results.

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