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Study Explains Weight Gain with Diabetes Therapy

Mar 1, 2013

Weight gain from intensive glucose-lowering treatment is more likely in patients….

The results from new data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, was recently published.

Lead author Vivian Fonseca, MD, from the Tulane University Health Science Center in New Orleans, Louisiana stated that, "The take-away message for clinicians is that when you have a patient whose diabetes is uncontrolled and start controlling it fairly rapidly, the patient is likely gain weight."

"You want to initiate strategies that have been tried in other trials to minimize weight gain [and] give people general advice about healthy living. I believe it is possible to lose weight on insulin or TZD," he said.

It is well known that intensive glucose lowering is linked with weight gain, but the reasons for this outcome remain unclear, the authors write.

To investigate this phenomenon, they performed a post hoc analysis of data from the ACCORD trial, which randomized patients with type 2 diabetes and other cardiovascular risk factors to intensive glucose lowering (an A1C target of <6%) or standard glucose lowering (an A1C target of 7.0% to 7.9%).

The researchers examined weight gain in the more than 90% of the trial participants — 4425 in the intensive-control group and 4504 in the standard-control group — with available weight and A1C values at 2 years of follow-up.

They aimed to determine whether the weight gain was explained by:

  • Baseline characteristics, including prior medications.
  • Change in A1C values.
  • Postrandomization medications.
  • Similar factors in the intensive- vs. standard-glucose-control groups.

Using multivariate analysis, they found that in both study groups, baseline characteristics of younger age, male sex, Asian race, no smoking history, high A1C levels, body mass index (BMI) of 25 to 35, large waist circumference, insulin use, and metformin use were independently linked with weight gain at 2 years.

In both treatment groups, participants with the highest baseline A1C levels tended to gain weight as A1C levels improved. In contrast, participants whose A1C levels were less than 7.8% at baseline lost weight when their A1C levels dropped during treatment, although the drop in A1C and in weight were relatively small. "Thus, in clinical practice, an attempt to intensify treatment in patients with a very high A1C is likely to lead to a significant weight gain," Dr. Fonseca wrote.

Insulin and TZDs had the greatest effect on weight gain, and changes in weight were more marked among the participants in the intensive-glycemia-control group. Participants in the intensive-control group who had never previously used TZD or insulin and who began the drug combination during this trial gained 4.6 to 5.3 kg at 2 years. In contrast, participants in this group who never took insulin or TZD had an average weight loss of 2.9 kg in the first 2 years of the trial.

"That is not totally surprising, since those drugs are known to cause weight gain," Dr. Fonseca said. "Medication use and all these studied factors, however, accounted for less than 15% of the variability" in weight gain, he pointed out. Other factors that play a role remain to be elucidated.

John Buse, MD, from the University of North Carolina, Chapel Hill, added that, the weight gain with insulin and TZD and the other study findings were "not really surprising. … Weight gain is common in patients with type 2 diabetes whose blood sugar control is improved with certain diabetes drugs (glitazones and insulin). … However, it should be noted that there are other drugs that are not associated with weight gain."

Although it is not likely to change clinical practice, the study does provide "more precision…about the multifactorial nature of weight gain in an important study — ACCORD," he concluded.

Diabetes Care. Published online February 14, 2013. Abstract