ADA: Glycemic Control Markedly Improved with Duodenal-Jejunal Sleeve

By John Geve
SAN FRANCISCO, 11 june 2008-- For obese patients with diabetes, a Teflon-like sleeve placed inside the small intestine just beyond the stomach seems to improve glycemic control quickly and markedly, a researcher said here In a small study, the investigational two-foot-long bypass prevented food from coming into contact with the duodenum and upper jejunum, reported Christopher H. Sorli, M.D., of the Billings Clinic in Billings, Mont., at the American Diabetes Association meeting. The impermeable fluoropolymer sleeve is placed via an endoscope and fastened with a barbed metal anchor at the duodenal entrance. The 16 patients in the study had a mean baseline BMI of 38 and a hemoglobin A1c of 9%.
After only one week, the daily average glucose level declined 58.4 mg/dL (SD 54.5 mg/dL) among 11 patients receiving the bypass sleeve, compared with an increase of 1.1 mg/dL (SD 45.7 mg/dL) in five sham-treated patients (P<0.05), according to interim results.
There were similar changes in average fasting plasma glucose levels in the two groups one week after placement, but the difference did not reach statistical significance.
Among eight patients receiving the sleeve for whom follow-up data were available at 31 weeks, glycosylated hemoglobin levels fell by 2.9 percentage points, from a baseline level of 8.9%, Dr. Sorli reported. For three sham-treated patients with 31-week data, hemoglobin A1c levels fell 0.76 percentage points (P=0.04).
"[The sleeve] rapidly improves glycemic control in type 2 diabetes as early as one week, independent of weight loss," he said.
The sham treatment involved sedation and endoscopy, but no sleeve was placed. In both groups, patients were on a liquid pureed-food diet for the first two weeks, advancing to solid food as tolerated.
All patients also were counseled to keep daily food intake to 1,200 calories for women and 1,500 calories for men.
Most patients receiving the sleeve were able to stop their previous diabetes medication, he added.
At baseline, seven of the patients were taking metformin alone and another four were on metformin and a sulfonylurea drug.
After 12 weeks, just one patient remained on metformin and none were taking sulfonylureas.
In the sham group, three of five patients evaluable at week 12 were still on oral medication.
Dr. Sorli said the sleeve is designed to mimic the effects on glycemia seen with Roux-en-y gastric bypass surgery, but less invasively.
Exactly how the sleeve affects glycemia is unclear, as the case for bypass surgery. "There's something happening in the small bowel that if you interact with it correctly, it has potential benefits, particularly for blood sugar control," Dr. Sorli said.
A number of studies in bypass patients have suggested that it involves the so-called incretin pathway that is now the target for several new diabetes drugs.
Patients lost weight with the sleeve, but a difference from sham treatment did not appear until several months into the study.
At week 12, mean weight loss relative to baseline was 7.76 kg in the sham-treated group and 8.55 kg with the sleeve.
But there was no further weight loss in the sham arm, whereas patients receiving the sleeve lost a total of 11.44 kg from baseline at week 20, Dr. Sorli said.
Dr. Sorli said the sleeve came loose and began migrating in three patients. In all cases, it was successfully retrieved through endoscopy.
Other adverse events included 8 cases of abdominal pain, three cases each of diarrhea and vomiting, two incidents of hypoglycemia, and one of nausea.
Dr. Sorli said the sleeve's design has not been finally established. "This is a pilot study, and there are so many variables we need to explore," he said. "Would longer be better? Would shorter be better? We don't know the answer to that. We also don't know the answer to how long we can leave it in."
He said leaving them in place for six months is now being studied, and even longer trials will probably be undertaken, he said.
Richard Pratley, M.D., a diabetologist at the University of Vermont in Burlington, said the concept seemed promising.
The prospect of a shorter and easily reversible procedure without general anesthesia would be an advantage over gastric bypass, he said. "Bypass surgery is big surgery," he said.
He said additional data on the safety and tolerability would be important.
Dr. Pratley also questioned whether the efficacy stemmed more from changes in patients' diet than from the device itself.
"Anything where you stop eating will lower your glucose. There may not be anything magical behind it," he said.
However, Dr. Sorli said that patients could eat as much as they did previously, and many probably did. Unlike gastric bypass or banding procedures, the sleeve does not physically restrict how much patients can eat, he said.
The study was supported by GI Dynamics, developer of the bypass sleeve.
Dr. Sorli reported relationships with GI Dynamics, GlaxoSmithKline, Eli Lilly, Novo Nordisk, Takeda, Merck, sanofi-aventis, and Covidian.
Dr. Pratley reported relationships with GlaxoSmithKline, Eli Lilly, Novo Nordisk, Takeda, Merck, sanofi-aventis, Novartis, and Roche Diagnostics.
Primary source: American Diabetes Association meetingSource reference:Tarnoff M, et al "Interim report on a prospective, randomized sham controlled trial investigating a completely endoscopic duodenal-jejunal bypass sleeve for the treatment of type 2 diabetes" ADA Meeting 2008; Abstract 32.