Diet and exercise beat metformin at preventing diabetes

By Kathryn Doyle

NEW YORK (Reuters Health) - In a head-to-head comparison over 15 years, diet and exercise outperformed metformin in preventing diabetes in patients at high risk.

"The lifestyle intervention was more powerful in preventing or delaying diabetes development during the original three-year Diabetes Prevention Program and remains more powerful over the entire 15-year study," David M. Nathan of George Washington University told Reuters Health by email.

"However, there are specific subgroups in which the lifestyle intervention had an even more powerful effect - specifically, those older than age 60," Nathan said.

Metformin was relatively more effective in people younger than 60 and those who were more obese, added Nathan, who is based in Rockville, Maryland.

The researchers followed up with the surviving participants of a diabetes prevention study conducted between 1996 and 2001 in which they had been randomly assigned to either an intensive lifestyle intervention, or metformin, 850 mg twice daily, or a placebo.

The participants were all overweight or obese and had elevated blood sugar levels.

At the end of that study, the people following the lifestyle intervention, which included a low-fat, low-calorie diet and 15 minutes of moderate-intensity exercise daily, had a 58% lower risk of diabetes compared to the placebo group. Those taking metformin were 31% less likely to have progressed to diabetes than those on placebo.

Since the lifestyle intervention had worked so well, all participants were offered a version of it for one year after the study concluded.

As of 2014, almost 90% of the original group, or 2776 people, had been followed since the end of the first study, and based on their original group assignments, they were offered lifestyle reinforcement seminars twice yearly or continued to receive metformin.

After an average of 15 years, diabetes incidence was lower by 27% in the lifestyle intervention group and 18% in the metformin group, compared to the placebo group.

In 2014, 55% of the lifestyle group, 56% of the metformin group, and 62% of the placebo group had been diagnosed with diabetes, the authors reported online September 13 in the Lancet Diabetes & Endocrinology.

The researchers found no difference between the groups in microvascular changes in the kidney and retina or in nerve damage over time. But among women in particular, the lifestyle group was less likely to show this kind of damage.

People who did not develop diabetes were almost 30% less likely to have kidney, retina, or neuropathy than those who did.

"The complications that we were studying represent the early manifestations of this microvascular disease and were generally asymptomatic," Nathan said. "It usually takes 10-20 years for these complications to become clinically serious."

It was surprising that although lifestyle changes reduced the risk of diabetes, they did not always reduce the risk of microvascular complications, Dr. Anoop Misra, director of Diabetes and Metabolic Diseases for Diabetes Foundation India, who authored a commentary alongside the new results, told Reuters Health by email.

"Metformin could be especially useful in people who are unable to follow diet and exercise strictly, who are obese, have polycystic ovarian disease, or cannot walk or exercise due to physical infirmity," Misra said. "It is a low-cost drug, and could be useful in underprivileged populations also."

As the American Diabetes Association recommends, Nathan said, lifestyle interventions should be the first choice for diabetes prevention, with metformin recommended for younger and more obese people.

The National Institute of Diabetic and Digestive and Kidney Diseases funded this research.

SOURCE: http://bit.ly/1iIGAO8

Lancet Diabetes Endocrinol 2015.

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