ECE2023 Poster Presentations Diabetes, Obesity, Metabolism and Nutrition (159 abstracts)
Effects of a combinatory treatment with semaglutide and a NPY Y2 receptor selective PYY 3-36 analogue in diet-induced obese rats: surpassing bariatric surgery?
Marie Oertel 1 , Julia Theisen 2 , Katharina Ecker 2 , Michael Kohlhaas 2 , Alexander Nickel 2 , Martin Fassnacht 1 , Christioph Maack 2 , Vasco Sequeira 2 & Ulrich Dischinger 1
1University Hospital Würzburg, Division of Endocrinology and Diabetes, Würzburg, Germany; 2University Hospital Würzburg, Comprehensive Heart Failure Center, Würzburg, Germany
Background: Combinatory treatments with analogues of incretins might mimic the beneficial effects of bariatric surgery. We could show in the past that a combinatory treatment with PYY 3-36 and liraglutide leads to a similar body weight loss as Roux-en-Y gastric bypass (RYGB). We hypothesize that a combination of semaglutide and a modified PYY 3-36 analogue with increased selectivity for the neuropeptide Y receptor type 2 (NNC0165-1273) exceeds the weight-reducing effects of bariatric surgery.
Methods: High-fat (45%) and high-fructose diet (HFD)-induced (8 weeks) obese male Wistar rats were randomized into the following treatment groups: (1) NNC0165-1273+semaglutide, (2) semaglutide, (3) saline. NNC0165-1273 was given continuously via osmotic minipump (0.08 µmol/kg/d), semaglutide was given once daily s.c. at a dose of 120µg/kg. Animals were kept on a free choice high- and low-fat diet after start of the respective intervention. Body weight and food preference were measured daily for 8 weeks post intervention.
Results: NNC0165-1273+semaglutide treatment led to an impressive and long-lasting body weight loss (max. -23.9%), which was superior to semaglutide monotherapy (max. -9.9%) and saline treatment (+8%). Compared to an earlier study with diet-induced obese rats, NNC0165-1273+semaglutide was even more effective than RYGB. Additionally, NNC0165-1273+semaglutide led to a strong decrease of HFD preference.
Conclusions: A combination of NNC0165-1273 and semaglutide is highly effective in terms of body weight loss in diet-induced obese rats and might be superior to the weight reducing effects of RYGB.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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