In findings that promise radical changes in the care of the 20 million U.S. patients with Type 2 diabetes, two new clinical trials have shown that weight-loss surgery brings about dramatically greater improvement of blood sugar control in obese diabetics than standard diabetes care.
In both studies, even rigorously supervised regimens of diet, exercise and medications failed to bring blood sugar under good control after a year or more. In contrast, two teams of researchers — one in Italy, the other in the United States — reported that surgical procedures to reduce the size and sometimes the placement of the stomach often allowed subjects to discontinue diabetes medications within weeks.
Both studies were published online Monday in the New England Journal of Medicine. One of them, by researchers at the Cleveland Clinic and Harvard University, was presented Monday at the American College of Cardiology's annual meeting in Chicago.
In an accompanying editorial in the journal, diabetes specialists Paul Zimmet and K. George M.M. Alberti wrote that although surgical weight-loss procedures were "not yet" a panacea for the worldwide epidemic of Type 2 diabetes, the new research "suggests they should not be seen as a last resort."
"Such procedures might well be considered earlier in the treatment of obese patients with Type 2 diabetes," Zimmet and Alberti wrote. Zimmet is a specialist at the Baker IDI Heart and Diabetes Institute in Melbourne, Australia, and Alberti is at King's College in London.
"Now we know that treating diabetes can — and should — be a primary reason for doing this surgery," said Dr. Lee M. Kaplan, director of the Massachusetts General Hospital Weight Center. Such surgery should not be the first line of treatment, Kaplan said, but it should become a fallback for patients whose blood sugar control remains poor despite medications and lifestyle changes.
"We ought to be using it more," he said.
Both studies examined patients who had undergone one of three bariatric surgery procedures: biliopancreatic diversion, Roux-en-Y gastric bypass or sleeve gastrectomy. In addition to improved blood sugar control, all experienced significantly greater weight loss than those on standard drug treatment.
Both studies also reported that subjects who had surgery saw more improvement in some, though not all, cholesterol measures than those on standard diabetes therapy.
In general, the studies found that the scale of improvements in patients' metabolic function and weight loss tracked the degree to which the surgical procedures reshaped the gastrointestinal system. Biliopancreatic diversion, the most radical of the operations, appeared to produce the most radical improvements, followed by Roux-en-Y bypass and sleeve gastrectomy.
Neither study looked at lap-band surgery, which is less invasive and accounts for a large proportion of bariatric procedures in the U.S.
In biliopancreatic diversion, part of the stomach is removed to reduce its capacity; in Roux-en-Y bypass, the stomach is shrunk by stapling off a large part of it. In both procedures, the stomach is relocated so that its contents are routed past much of the lower intestine, where the most calories and nutrients are absorbed.
Sleeve gastrectomy does not move the stomach or alter the way food enters or leaves it; but it does refashion the stomach into a banana-shaped tube with about 20% of its former capacity.
The U.S. study examined 150 people, 100 of whom received surgery — half had sleeve gastrectomy and half had Roux-en-Y gastric bypass — and 50 who got intensive medication, monitoring, and diet and exercise counseling.
Those in the surgery group dramatically reduced their need for medication of all kinds. Many subjects were taking 10 to 12 medications daily, including insulin injections, said Dr. Philip R. Schauer, director of the Cleveland Clinic Bariatric and Metabolic Institute and lead author of the study.
At the end of one year, 78% of those who had gastric bypass and 51% of those who had sleeve gastrectomy were off all diabetes medications. The proportion of subjects taking lipid-lowering medication such as a statin dropped from 86% to 27% among those who had gastric bypass, and was cut in half among those who had sleeve gastrectomy.
"Were they happy? They were ecstatic," Schauer said. "With one, single intervention, the patient gets so much benefit."
In the Italian study, 60 obese diabetic patients were divided into three groups: one got "conventional care," including medications; a second group underwent Roux-en-Y bypass; and a third had biliopancreatic diversion.
At two years, 95% of those in the biliopancreatic diversion group experienced a remission of their diabetes, as did 75% of those in the Roux-en-Y group. Though blood sugar control improved in the conventional therapy group, there were no remissions among those subjects.
About 220,000 bariatric surgery procedures are performed each year in the U.S., a number that has grown steeply with the rise in obesity rates and the number of centers performing the procedures.
The procedures in these studies can cost $10,000 to $43,000, depending on complications. But Schauer said that the many medications that people with diabetes take over their lifetimes — as well as the monitoring of their effects — also are costly.
Patient safety has been a growing concern with the proliferation of facilities providing bariatric procedures. In the U.S. study, at least, the rate of serious complications was on the low side of the national average: four of the 100 patients required corrective surgery. In the Italian study, two of 40 patients who had surgery required another operation.
Major questions about the subjects' long-term health remain unanswered because they were tracked for only one or two years, depending on the study. The complications of Type 2 diabetes — kidney failure, vision loss, amputations, stroke and heart disease — can take years to show up.
Still, researchers said that significant improvement in glucose control should translate into fewer of diabetes' most life-threatening consequences: heart attack and stroke. Both studies showed that, compared with those receiving conventional therapy, subjects who had surgery saw marked improvements in blood lipids — measures such as triglycerides and "good" and "bad" cholesterol.
"We don't know what is going to happen five or 10 years down the road. But from a one-year perspective, their diabetes is gone," said Dr. Steven Nissen, a Cleveland Clinic cardiologist and coauthor of the U.S. study. "For a disease that is ravaging this country, to have their blood sugar normalized is astonishing."
The studies brought enthusiasm and a few reservations from diabetes experts, who noted that evidence for bariatric surgery's effectiveness in treating diabetes has been accumulating for some time. But the two new studies, unlike earlier ones, were randomized controlled trials — considered the gold standard for comparing competing treatments.
" 'The most effective treatment right now for diabetes is surgery' — you can now use that sentence," said Dr. Daniel Bessesen, chief of endocrinology at the University of Colorado Hospital in Denver. "This is a big deal."
But he cautioned that it was far too soon to suggest that patients were "cured" of their diabetes, given the studies' short follow-up period.
And, he said, given the expense of weight-loss surgery and its risks, physicians, insurers and patients probably will spend years trying to figure out who should get the surgeries at the limited number of hospitals and centers that perform them, and how the procedures should be paid for.
As more people undergo bariatric surgery for diabetes, primary care physicians will need to become more attentive to the post-operative health issues of such patients, Bessesen said.
These include nutritional deficiencies (because patients' altered gastrointestinal tracts absorb fewer vitamins and minerals), bone health (because calcium absorption is changed), kidney stones, gallstones and hernia. Physicians will also need to learn how to respond if patients start to regain weight, which can happen in the years after surgery.