Affiliation:
1. Zydus Research Centre, Cadila Healthcare Limited, Moraiya, Ahmedabad,
India
Abstract
Abstract
Background Obesity and diabetes are major metabolic disorders that
progress to severe morbidity and mortality. Neuroendocrine mechanisms
controlling energy balance indicate that combination therapies are needed to
sustain weight loss. Lorcaserin was one of the approved therapies for the
treatment of obesity, which is recently withdrawn because a safety clinical
trial, shows an increased occurrence of cancer. Coagonist of
glucagon-like-peptide-1 (GLP-1) and glucagon receptors is a novel
investigational therapy demonstrated to have both anti-obesity and
anti-diabetic effect. Here, we investigated the effect of combination of
lorcaserin and a GLP-1 and glucagon receptors coagonist in diet-induced
obese (DIO) mice model.
Methods The diet-induced obese C57BL/6J mice were used to
assess acute and chronic effect of lorcaserin, coagonist of GLP-1and
glucagon receptors and their combination on food intake, body weight, and
biochemical parameters.
Results In acute study, combination of lorcaserin and coagonist
causes synergistic reductions in food intake and body weight. Repeated
treatment of combination of lorcaserin and coagonist showed enhanced body
weight loss over time, which is due to reduction in fat mass (subcutaneous,
retroperitoneal, mesenteric and epididymal fat pad) compared to individual
therapy. Also, suppression of locomotor activity seen with lorcaserin was
not evident in combination with coagonist. No additive effect was observed
in glucose tolerance (intraperitoneal glucose tolerance test or insulin
tolerance test), serum lipids, hepatic lipids, and energy expenditure in
combination group.
Conclusion These data suggest that combination of lorcaserin and
coagonist could be a better combination to induce body weight loss.
Subject
Drug Discovery,General Medicine
Cited by
1 articles.
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