‘Medical bypass’ with triple gut-hormone infusion reduces glucose levels, body weight
SAN FRANCISCO — Among adults with prediabetes or type 2 diabetes and obesity, subcutaneous infusion of the gut hormones GLP-1, oxyntomodulin and peptide YY led to improved glucose levels and weight loss vs. placebo and less glucose variability vs. Roux-en-Y gastric bypass, according to a speaker here.
The effects of Roux-en-Y gastric bypass on the gut hormones GLP-1, oxyntomodulin (OXM) and peptide YY (PYY) may be responsible for the diabetes remission and weight loss observed in patients who have undergone the surgery, according to Tricia M. Tan, BSc, MBChB, FRCP, PhD, FRCPath, professor of practice in metabolic medicine and endocrinology, Imperial College Healthcare NHS Trust and Imperial College London, and colleagues. The researchers examined the effects of achieving the same postprandial gut hormone levels via a continuous subcutaneous infusion of the hormones in patients who had not had the surgery.
“We could call this a ‘medical bypass,’ ie, mimicking postbariatric surgery hormone changes without the surgery,” Tan told Endocrine Today.
In a randomized, single-blind trial, Tan and colleagues administered the triple-hormone combination, dubbed GOP, to 15 participants (six women; mean BMI, 38.4 kg/m2; 13 with diabetes; two with prediabetes; seven prescribed metformin) via a Cane Crono infusion pump and a Medtronic infusion set. Participants were instructed to continue the infusion for 12 hours per day for 4 weeks from 1 hour before breakfast until after their last meal of the day. A placebo group with 11 similar adults (five women; mean BMI, 39.2 kg/m2; eight with diabetes; three with prediabetes; five prescribed metformin) followed the same protocol with saline.
The researchers recorded fructosamine levels and body weight at baseline and 4 weeks and mean glucose levels and variability via continuous glucose monitoring; they measured glucose and insulin levels during a mixed-meal test; and they assessed energy expenditure and energy intake.
Researchers compared results for the GOP group against those for a group of 21 adults who had undergone gastric bypass and 22 adults assigned to a very low-calorie diet of 800 kcal per day.
At week 4, the GOP group saw greater weight loss from baseline vs. placebo (GOP, –4.4 kg; 95% CI, –5.4 to –3.5; placebo, –2.5 kg; 95% CI, –4.1 to –0.9). The gastric bypass group lost –10.3 kg (95% CI, –11.8 to –8.8) and the diet group lost –8.3 kg (95% CI, –9.5 to –7.1).
At week 4, the GOP group had a greater mean absolute reduction in fructosamine vs. the placebo group (–44.1 µmol/L; 95% CI, 62.7 to –25.5 vs. –11.7 µmol/L; 95% CI, –18.9 to –4.5) and similar reductions to those in the gastric bypass (–34 µmol/L; 95% CI, –45.6 to –22.4) and diet groups (–28.5 µmol/L; 95% CI, –40.4 to –16.7).
During the week before baseline and week 3, all groups except the diet group wore a CGM for 7 days under free-living conditions. The GOP group had a mean glucose reduction of –3.6 mmol/L (95% CI, –5.2 to –1.9) vs. no reduction for the placebo group. The gastric bypass group had a –2.5 mmol/L reduction (95% CI, –3.6 to –1.4).
Glucose variability was significantly improved for the GOP group vs. the placebo and gastric bypass groups, with mean amplitude glucose changes of –0.75, –0.1 and –0.1, respectively.
The GOP protocol “is safe and welltolerated and deliverable in a ‘freeliving’ context,” Tan said. “We observed good weight loss with the GOP infusion, there is a continuing reduction in food (energy) intake, and there is no tachyphylaxis, ie, a diminution of effect as time goes on.”
During the mixed-meal test, the researchers observed a “flat euglycemic response” with no sharp insulin peak in the GOP group vs. an early glucose peak with notable insulin secretion in the gastric bypass group, according to Tan.
“We saw much less glucose variability with the GOP infusion compared to patients with gastric bypass, which may well translate to reduced vulnerability to hypoglycemia,” Tran said. – by Jill Rollet
Tran TM, et al. 57-OR. Presented at: American Diabetes Association 79th Scientific Sessions; June 7-11, 2019; San Francisco.
Disclosure: Tan reports a relevant financial relationship with Novo Nordisk A/S.