Intestinal Sleeve May Improve Glycemic Control

By Kristina Fiore, Staff Writer, MedPage Today
Published: November 16, 2009
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Noninvasive implantation of a sleeve in the small intestine just beyond the stomach quickly improves glycemic control in obese diabetes patients, researchers say.
In a small pilot study, fasting plasma glucose levels for patients who received the duodenal-jejunal bypass liner (EndoBarrier) fell 55 mg/dL, while levels among those who had a sham procedure rose 42 mg/dL (P≤0.05), according to Christopher Sorli, MD, of the Billings Clinic in Billings, Mont., and colleagues.

They reported their findings online in Diabetes Technology & Therapeutics.

But differences in this measure of glycemic control did not remain significant after the 24 weeks of the study were completed. Also, the study was scheduled to run for 52 weeks but too many patients had to have the device removed because of pain or anchor migration before that time.

Still, the researchers said the results are hopeful.

"The ability of the [sleeve] to rapidly normalize glycemic control in obese diabetes patients represents a promising development in the search for novel therapies that provide relief to the clinical progression of this disease and are less invasive than bariatric surgery," the researchers said. "The results of this diabetes-specific pilot study are encouraging and support further clinical investigations."

Although bariatric surgery has been effective in reversing diabetes, particularly with regard to normalization of plasma glucose, insulin, and HbA1c, some concerns exist about its associated morbidity and mortality.

So researchers have been looking for an alternative. The duodenal-jejunal bypass liner is a candidate because it is placed endoscopically and is easily removable. It's also made of an impermeable fluoropolymer sleeve and is fastened in place via a barbed metal anchor at the duodenal entrance.

For 24 weeks between January 2007 and February 2008 at the Hospital DIPRECA in Santiago, Chile, the researchers studied 18 obese diabetic patients -- 12 of whom received the sleeve, and another six who got sham endoscopy.

They looked at baseline weight, HbA1c, a meal tolerance test, fasting glucose, and seven-point glucose profiles.

At baseline, all patients were taking at least one oral diabetes drug. Their baseline HbA1c was 9.1 and baseline body mass index (BMI) was 38.9.

The researchers found that within the first week, the device reduced fasting plasma glucose by 55 mg/dL in the sleeve group, while those in the sham group had a 42 mg/dL increase (P≤0.05).

By the end of the study, fasting plasma glucose dropped 83 mg/dL in the treatment group and rose 16 mg/dL in the sham group, but this difference was not significant.

Also at one week, mean postprandial glucose area-under-the-curve was reduced in the treatment group by 22% and was increased 16% in the sham arm (P=0.016).

Meanwhile, the seven-point glucose profile was reduced and flattened at one week but was not changed in the sham group, the researchers said.

Although HbA1c decreased substantially more in the device arm than in the sham arm, the trial missed its primary endpoint because this difference did not reach statistical significance.

At week 12, HbA1c dropped 1.3% in the treatment group and 0.8% in the sham arm, and at 24 weeks, it dropped 2.4% in the treatment group and 0.7% in the sham group, with no significant differences at either time point.

But the device did appear to reduce the number of oral diabetes medications patients were taking.

In the intent-to-treat population, after 12 weeks, 42% of patients with the sleeve were able to stop their diabetes medications, compared with only 17% of those in the placebo group who quit their drugs.

In the full population, after 12 weeks, 50% and 25% had ceased use, respectively.

By week 24, 40% of treated patients and 25% of sham patients remaining in the study had stopped taking diabetes medications.

The researchers said that device migrations required endoscopic removal before the 52-week mark.

Three patients had the sleeve removed after an adverse event related to migration or turning, including moderate abdominal pain and moderate nausea and vomiting.

Two other migrations occurred but the patients had no symptoms, they added.

They noted that all 12 treated patients had at least one episode of mild or moderate abdominal pain and four of them had mild or moderate vomiting, but none requested the device be removed for these reasons.

Weight loss was also similar in both groups. The device arm tended towards more weight loss after week 12, but this was not statistically significant because the study was designed to minimize differences in weight loss between groups so the researchers could analyze glycemic changes independent of weight loss.

Patients with the device began to lose more weight, but because of the small number of patients in the sham arm and because one of them lost a significant amount of weight, the differences didn't reach statistical significance.

The study was limited in its statistical power and by the need to remove three devices due to abdominal pain or anchor migration.

http://www.medpagetoday.com/Endocrinology/Diabetes/17008_