BERLIN – Gastric banding surgery and metformin produce similar improvements in insulin sensitivity and parameters indicative of preserved beta-cell function in patients with impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetes mellitus (T2DM), according to the results of a study conducted by the Restoring Insulin Secretion (RISE) Consortium.
“Both interventions resulted in about 50% improvements in insulin sensitivity at 1 year, which was attenuated at 2 years,” reported study investigator, of the University of Southern California, Los Angeles, at the annual meeting of the European Association for the Study of Diabetes.
“The beta-cell responses fell in a pattern that maintained relatively, but not perfectly, stable compensation for insulin resistance,” he added.
Although glucose levels improved “only slightly,” he said, “acute compensation to glucose improved significantly with gastric banding and beta-cell compensation at maximal stimulation fell significantly with metformin.”
Results of theBeta Cell Restoration through Fat Mitigation) study, which are now published online in , also showed that greater weight loss could be achieved with surgery versus metformin, with a 8.9 kg difference between the groups at 2 years (10.6 vs. 1.7 kg, respectively, P less than .01).
HDL cholesterol levels also rose with both interventions, and gastric banding resulted in a greater effect on very low–density lipoprotein cholesterol and triglycerides, as well as serum ALT, Dr. Buchanan said.
The BetaFat study is one of three “proof-of principle” studies currently being conducted by the RISE Consortium in patients with IGT, sometimes called prediabetes, and T2DM, explained Steven E. Kahn, MB, ChB, the chair for the RISE studies.
The other two multicenter, randomized trials being conducted by the RISE Consortium are looking at the effects of medications on preserving beta-cell function in pediatric/adolescent (10-19 years) and adult (21-65 years) populations with IGT or mild, recently diagnosed T2DM. The design, and some results, of these trials can be viewed on a.
Beta-cell function is being assessed using “state-of-the-art” methods; the coprimary endpoint of the surgery versus metformin study was the steady state C-peptide level and acute C-peptide response at maximal glycemia measured using a hyperglycemic “clamp.”
The goal of the RISE studies is to test different approaches to preserve beta-cell function. It is designed to answer the question of which is more effective in this setting: sustained weight loss through gastric banding such as in the BetaFat study or medication.
Patients were eligible for inclusion in the study if they were aged 21-65 years, had a body mass index of 30-40 kg/m2, and had IGT or a diagnosis of T2DM within the past year for which they had received no diabetes medication at recruitment.
A total of 88 individuals were randomized with exactly half undergoing gastric banding. This consisted of a gastric band placed laparoscopically and adjusted every 2 months for the first year, and then every 3 months for the following year depending on symptoms and weight change.
Normoglycemia was observed in none of the study subjects at baseline but in 22% and 15% of those who had gastric banding or metformin, respectively, at 2 years (P = .66).
As for tolerability, five patients who underwent gastric banding experienced serious adverse events, of which two were caused by band slippage and three were caused other reasons. In the metformin arm, there were two serious adverse events, both unrelated to the medication.
“Gastric banding and metformin offered approximately equal approaches for improving insulin sensitivity in adults with mild to moderate obesity and impaired glucose tolerance or early, mild type 2 diabetes,” Dr. Buchanan concluded. “The predominant beta-cell response was a reduction in secretion to maintain a relatively constant compensation for insulin resistance, with only a small improvement in glucose. Whether these interventions will have different effects on beta-cell function over the long-term remains to be determined.”
Commenting on the study,, professor of medicine and metabolism at Newcastle University (England), noted that the changes in the lipid and liver parameters were important. Fasting plasma triglyceride levels fell from 1.3 mmol/L at baseline to 1.1 mmol/L at 2 years with surgery but stayed more or less the same with metformin (1.23 mmol/L and 1.28 mmol/L; P less than .009 comparing surgery and metformin groups at 2 years). Change in ALT levels were also significant comparing baseline values with results at 2 years, decreasing in the surgical group to a greater extent than in the metformin groups.
“There’s a really important message here, the predictors of a better response to the weight loss [i.e. changes in triglycerides and liver enzymes] are all there,” Dr. Taylor observed. “RISE has looked at 2 years of this effect, but the conversion to type 2 diabetes is probably going to happen over a longer time course.”
He added that “although the primary outcome measure of change in insulin secretion was not achieved, the writing is on the wall. These people, provided they maintain their weight loss, are likely to succeed. We see all the hallmarks of a successful outcome for the weight loss group – remove the primary driver for type 2 diabetes, and that group is on track.”
The RISE Consortium conducted the BetaFat study. The RISE Consortium is supported by grants from the National Institutes for Health. Further support came from the Department of Veterans Affairs, Kaiser Permanente Southern California, the American Diabetes Association, and Allergan. Additional donations of supplies were provided by Allergan, Apollo Endosurgery, Abbott, and Novo Nordisk. Dr. Buchanan reported receiving research funding from Allergan and Apollo Endosurgery. Dr. Taylor had no conflicts of interest.