The drug Glucophage (metformin), as well as diet and exercise programs, are effective diabetes prevention measures, according to the National Institute of Diabetes and Digestive and Kidney Diseases. But the strategies tested in the new study, which included stronger medications typically reserved for people with full-blown type 2 diabetes, did not help people with prediabetes once they went off the medications. “We see benefits, as expected. But the question is could we sustain the results, and the answer is we couldn’t,” says an author of the study, Kieren J. Mather, MD, a professor of medicine in the division of endocrinology and metabolism, and an associate director of the Diabetes Translational Research Center at Indiana University School of Medicine in Indianapolis. “We’re identifying a group of people at risk and trying to find something to do that preserves beta-cell function and prevents them from progressing," Dr. Mather says. “What is it that we can offer that can make a difference?" RELATED: Is Prediabetes a Useful Diagnosis? A New Article Revives an Old Debate
After 12 Months on the Medication and 3 Months Off, Benefits Disappeared
The study, Restoring Insulin Secretion (RISE), was designed to look at whether beta cells could recover and function normally after people with prediabetes were treated for a limited time with diabetes medications. Beta cells are cells in the pancreas that produce, store, and release the hormone insulin, according to Diabetes UK. Researchers assigned adults with prediabetes or early type 2 diabetes to one of four treatment regimens: placebo pills; metformin alone; a long-acting insulin therapy known as Lantus (insulin glargine) followed by metformin; or the drug Victoza (liraglutide), a glucagon-like peptide-1 receptor agonist (GLP-1), plus metformin, according to the study details. Healthcare providers don’t typically prescribe glargine and Victoza to people who have not yet developed type 2 diabetes. “Everybody got lifestyle recommendations because we were starting from the Diabetes Prevention Program as our background,” Mather says. Researchers followed participants for 12 months of active treatment and then reassessed them three months after participants stopped the therapy. Researchers looked at glucose tolerance during the therapy and following withdrawal of the therapy to see if any of the medication regimens resulted in a sustained benefit, such as recovery of beta cells or lower glucose levels. They found that people taking Victoza experienced the largest benefit while on the drug followed by modest effects from metformin and insulin glargine. Yet three months after stopping the medications, none of the subjects showed a lasting benefit. “At 15 months, everything is gone,” Mather says. “We were not able to induce sustained change.” Diabetes is a progressive disorder in which beta cells deteriorate. The study tested the idea that the cells could recover early in the course of the disease, says Alvin C. Powers, MD, a professor of endocrinology at Vanderbilt University School of Medicine in Nashville, Tennessee. Dr. Powers was not involved in the study. “The people studied in this were very early in the disease. There is this notion that if you rest the insulin cells, they would function better and you could delay or possibly stop any progression of the disease,” he says. “It was a well-done study designed to answer whether or not you change the natural history. I think it means that these specific drugs that were used cannot alter the natural history of the disease.” RELATED: Are You at Risk for Type 2 Diabetes?
What We Know — and Don’t Know — About Delaying Type 2 Diabetes
A similar study, which was published in August 2018 in Diabetes Care, in children and adolescents with impaired glucose tolerance or recently diagnosed type 2 diabetes, found that neither three months of glargine followed by nine months of metformin nor 12 months of metformin alone halted the progression of diabetes. That study suggested that halting diabetes progression in children and teens is particularly challenging. “For the kids, [the RISE Pediatric Medication Study] has been remarkable information for the world. It tells us that the kids’ disease is different and more aggressive. People need to look at what they’re going to do for the kids,” Mather said. As for adults with prediabetes, making diet and lifestyle changes is as effective as using metformin, notes an article published in March 2017 in the Journal of the American Medical Association. But the RISE study does not support the use of stronger medications, such as insulin or a glucagon-like peptide-1 receptor agonist, in people with prediabetes or very early diabetes. Victoza is an injection, he notes, and would have to be continued forever based on the results of the RISE study. “For the rest of your life, you should take this medicine of some sort? That is a steep hill to climb,” Mather says of people with prediabetes or early diabetes. “I don’t know how easy that will be, and maybe that’s not the right strategy. If you can do something aggressive for a short period of time, it’s more acceptable. But being aggressive for a long period is not as acceptable.”
