%0 Randomized Controlled Trial
%T Adaptive infusion of a glucagon-like peptide-1/glucagon receptor co-agonist G3215, in adults with overweight or obesity: Results from a phase 1 randomized clinical trial.
%A Hope DCD
%A Ansari S
%A Choudhury S
%A Alexiadou K
%A Tabbakh Y
%A Ilesanmi I
%A Lazarus K
%A Davies I
%A Jimenez-Pacheco L
%A Yang W
%A Ball LJ
%A Malviya R
%A Reglinska B
%A Khoo B
%A Minnion J
%A Bloom SR
%A Tan TM
%J Diabetes Obes Metab
%V 26
%N 4
%D 2024 Apr 16
%M 38229453
%F 6.408
%R 10.1111/dom.15448
%X <B>OBJECTIVE: </B>To determine whether a continuous infusion of a glucagon-like peptide receptor (GLP-1R)/glucagon receptor (GCGR) co-agonist, G3215 is safe and well tolerated in adults with overweight or obesity.<BR><B>METHODS: </B>A phase 1 randomized, double blind, placebo-controlled trial of G3215 in overweight or obese participants, with or without type 2 diabetes.<BR><B>RESULTS: </B>Twenty-six participants were recruited and randomized with 23 completing a 14-day subcutaneous infusion of G3215 or placebo. The most common adverse events were nausea or vomiting, which were mild in most cases and mitigated by real-time adjustment of drug infusion. There were no cardiovascular concerns with G3215 infusion. The pharmacokinetic characteristics were in keeping with a continuous infusion over 14 days. A least-squares mean body weight loss of 2.39 kg was achieved with a 14-day infusion of G3215, compared with 0.84 kg with placebo infusion (p < .05). A reduction in food consumption was also observed in participants receiving G3215 and there was no deterioration in glycaemia. An improved lipid profile was seen in G3215-treated participants and consistent with GCGR activation, a broad reduction in circulating amino acids was seen during the infusion period.<BR><B>CONCLUSIONS: </B>An adaptive continuous infusion of the GLP-1/GCGR co-agonist, G3215, is safe and well tolerated offering a unique strategy to control drug exposure. By allowing rapid, response-directed titration, this strategy may allow for mitigation of adverse effects and afford significant weight loss within shorter time horizons than is presently possible with weekly GLP-1R and multi-agonists. These results support ongoing development of G3215 for the treatment of obesity and metabolic disease.