An Alternative Option for Weight and Glycemia Reduction

GOP hormone infusion could help in reducing patient weight and glucose levels. 

Roux-en-Y gastric surgery (RYGB) is known to be the most efficacious treatment for obesity and type 2 diabetes (T2DM). Increased postprandial secretions of Glucagon-like peptide 1 (GLP-1), Oxyntomodulin (OXM), and peptide YY (PYY) are one of the possible mechanisms of weight loss. These gut hormones have a synergistic effect on decreasing food intake and increasing satiety. Previous studies have shown that a continuous subcutaneous infusion of those hormones led to a reduction in total ad libitum energy intake. The purpose of the study was to determine whether the infusion of the GLP-1 agonist, Oxyntomodulin, and peptide YY (GOP) would reduce body weight and improve glycemia.   

This study was a single-blinded randomized controlled study comparing two infusion groups (GOP or saline) in patients with obesity and prediabetes or T2DM. Two other nonblinded groups were recruited: patients undergoing RYGB, and patients following an 800 kcal/day (very low-calorie diet [VLCD]). Participants either received GOP (15 patients) or saline infusion (11 patients) for 28 days. Diabetes medications were discontinued at the time of the intervention. The infusion was run starting 1 hour before breakfast, lasting for 12 hours, and discontinued after their last meal. The RYGB group (21 patients) was followed at weeks 2, 4 and 12 after laparoscopic surgery. A dietician weekly followed the VLCD group (22 patients). RYGB and VLCD volunteers had similar weight (117.8 kg (P=0.56) vs. 109.0 kg (P= 0.65)) but baseline fructosamine levels were significantly different (250.3 mmol/L (P= 0.003) vs. 252.4 mmol/L (P= 0.004)). Most participants had diabetes (68–87%) and were evenly split between diet only  and metformin as treatment. All participants received healthy eating and weight loss counseling. A standardized mixed meal test (MMT) was administered before and at the end of each intervention. The primary outcome was a change in body weight at four weeks. Secondary outcomes were a change of glycemia (detected by fructosamine), change in ad libitum and 24-h total Energy intake, fasting and postprandial glucose and insulin levels in response to a mixed meal test, glucose variation as assessed by continuous glucose monitoring (CGM); and energy expenditure. Statistical tests were performed by using the unpaired student t-test for the primary and secondary outcomes. ANCOVA was used to access GOP vs. RYGB and GOP vs. VLCD.   

GOP reduced weight by an average of 4.4 kg, while the saline reduction was an average of 2.5 kg (p <0.05). RYGB weight loss was about 10.3 kg (CI 95% -7.5, -4.2), and VLCD was 8.3 kg (CI -5.3,2.4). Mean absolute reduction in fructosamine in the GOP group was 44.1 umol/L vs saline 11.7 umol/L (P = 0.0026, unpaired t-test) ANCOVA (P= 0.0001). RYGB’s reduction was 34 mmol/L vs. VLCD was 28.5 mmol/L. No significant difference was detected between the four arms regarding fructosamine reduction. The difference between GOP vs. saline regarding the reduction of fasting glucose was significant (p<0.05); the effect of RYGB vs. GOP (CI 95% 0.7,3.9); lastly, the effect of GOP vs. VLCD was not significantly different (CI 95% 0.3, 4.5). GOP significantly reduced mean glucose by 3.6 mmol/L, whereas the saline group saw no significant change in mean glucose (p<0.01). RYGB reduced mean glucose by 2.5 mmol/L, but it was not significantly different in comparison to GOP (CI 95% -9,3.0). Regarding mean amplitude glucose change (MAG), the GOP’s reduction was the only statistically significant data (p<0.001). An MMT was performed postintervention that revealed a significant reduction of glucose after GOP (CI 95% -1624·8, -600·3) and a reduction of insulin (CI 95% -5983·7, -845·8). RYGB also had a significant reduction in glucose (CI 95% 898·7, -381·5) but not in insulin (CI 95% 1503·3, 9493·8). VLCD’s reduction in insulin (CI 95% -818·4, -243·6) and in insulin (CI 95% -2906·6, – 234·3). The difference in reduction in 24-h energy intake between saline and GOP was not statistically significant. RYGB led to a numerically larger reduction in 24-h energy intake by 957.7 kcal/24 h, but this was not significantly larger than GOP. Resting energy expenditure was significantly reduced in the GOP group and the RYGB group only.  

Activity-related energy expenditure was significantly reduced after RYGB only. There was no significant reduction in diet-induced thermogenesis. The only side effect that the GOP group experienced was temporary, mild erythema around the infusion sites that resolved with improvements with better insertion technique. No hypoglycemic episodes were observed with the GOP group. However, the RYGB group had a documented glucose level that was less than 4.0 mmol/L (72 mg/dL).  

This study showed that GOP was successful in reducing weight and that the effect of reduction in the ad libitum was sustained over four weeks without tachyphylaxis. However, the ad libitum energy intake was not significantly different between GOP and saline. Study limitations were small sample size and a 4-week duration. One of the weaknesses of the study was that the VLCD patients did not undergo CGM; it would’ve been useful to see how diet changes can affect blood glucose levels. Future studies should focus on the GOP’s effect on insulin sensitivity. Additionally, future studies should have a longer duration to assess the impact on HbA1C.  

Practice Pearls:  

• An infusion of GLP-1 agonist, Oxyntomodulin, and Peptide YY’s can be helpful in weight loss.  
• GLP-1 agonist, Oxyntomodulin, and Peptide YY showed a significant reduction in fructosamine, which can improve glycemic control. 
• In contrast to Roux-en-Y gastric surgery, GOP has a lower chance of provoking hypoglycemia in patients.  

Behary, Preeshila, et al. “Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study.“ Diabetes Care, vol. 42, no. 8, 2019, pp. 1446–1453.  

Nour Salhab, Pharm.D. Candidate, USF College of Pharmacy