RT Journal Article SR Electronic T1 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 JF Diabetes Care JO Diabetes Care FD American Diabetes Association SP 1446 OP 1453 DO 10.2337/dc19-0449 VO 42 IS 8 A1 Behary, Preeshila A1 Tharakan, George A1 Alexiadou, Kleopatra A1 Johnson, Nicholas A1 Wewer Albrechtsen, Nicolai J. A1 Kenkre, Julia A1 Cuenco, Joyceline A1 Hope, David A1 Anyiam, Oluwaseun A1 Choudhury, Sirazum A1 Alessimii, Haya A1 Poddar, Ankur A1 Minnion, James A1 Doyle, Chedie A1 Frost, Gary A1 Le Roux, Carel A1 Purkayastha, Sanjay A1 Moorthy, Krishna A1 Dhillo, Waljit A1 Holst, Jens J. A1 Ahmed, Ahmed R. A1 Prevost, A. Toby A1 Bloom, Stephen R. A1 Tan, Tricia M. YR 2019 UL http://care.diabetesjournals.org/content/42/8/1446.abstract AB OBJECTIVE Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones (“GOP”), mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GOP on glycemia and body weight when given for 4 weeks to patients with diabetes and obesity.RESEARCH DESIGN AND METHODS In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (n = 15) or saline (n = 11) infusion for 4 weeks. We also studied 21 patients who had undergone RYGB and 22 patients who followed a very low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were 1) body weight, 2) fructosamine levels, 3) glucose and insulin during a mixed meal test (MMT), 4) energy expenditure (EE), 5) energy intake (EI), and 6) mean glucose and measures of glucose variability during continuous glucose monitoring.RESULTS GOP infusion was well tolerated over the 4-week period. There was a greater weight loss (P = 0.025) with GOP (mean change −4.4 [95% CI −5.3, −3.5] kg) versus saline (−2.5 [−4.1, −0.9] kg). GOP led to a greater improvement (P = 0.0026) in fructosamine (−44.1 [−62.7, −25.5] µmol/L) versus saline (−11.7 [−18.9, −4.5] µmol/L). Despite a smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose tolerance after a mixed-meal stimulus and reduced glycemic variability compared with RYGB and VLCD.CONCLUSIONS GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight.