A Placebo-Controlled Study on the Effects of the Glucagon-Like Peptide-1 Mimetic, Exenatide, on Insulin Secretion, Body Composition and Adipokines in Obese, Client-Owned Cats

Glucagon-like Peptide-1 mimetics increase insulin secretion and reduces body weight in humans. In lean, healthy cats, short-term treatment has produced similar results, whereas the effect in obese cats or with extended duration of treatment is unknown. Here, prolonged (12 weeks) treatment with the Glucagon-like Peptide-1 mimetic, exenatide, was evaluated in 12 obese, but otherwise healthy, client-owned cats. Cats were randomized to exenatide (1.0 μg/kg) or placebo treatment twice daily for 12 weeks. The primary endpoint was changes in insulin concentration; the secondary endpoints were glucose homeostasis, body weight, body composition as measured by dual-energy x-ray absorptiometry and overall safety. An intravenous glucose tolerance test (1 g/kg body weight) was conducted at week 0 and week 12. Exenatide did not change the insulin concentration, plasma glucose concentration or glucose tolerance (P>0.05 for all). Exenatide tended to reduce body weight on continued normal feeding. Median relative weight loss after 12 weeks was 5.1% (range 1.7 to 8.4%) in the exenatide group versus 3.2% (range -5.3 to 5.7%) in the placebo group (P = 0.10). Body composition and adipokine levels were unaffected by exenatide (P>0.05). Twelve weeks of exenatide was well-tolerated, with only two cases of mild, self-limiting gastrointestinal signs and a single case of mild hypoglycemia. The long-term insulinotropic effect of exenatide appeared less pronounced in obese cats compared to previous short-term studies in lean cats. Further investigations are required to fully elucidate the effect on insulin secretion, glucose tolerance and body weight in obese cats

Fasting plasma glucagon concentration.

<p>Fasting, plasma glucagon concentration in ten obese client-owned cats before and after 12 weeks of exenatide (broken lines, n = 5) or placebo (solid lines, n = 5) treatment. P = 0.25.</p

Individual differences in plasma insulin and glucose levels 120 minutes after a glucose bolus.

<p>Plasma insulin and glucose concentration 120 min after a 1 g/kg glucose bolus in six obese client owned cats randomized to the exenatide treatment group. Measurements were obtained before treatment initiation.</p

Biochemical blood analyses and hemograms before and after 12 weeks of treatment with either exenatide or placebo.

<p>Biochemical blood analyses and hemograms before and after 12 weeks of treatment with either exenatide or placebo.</p

Plasma insulin and glucose concentration in exenatide treated cats.

<p>Plasma insulin and glucose concentration during an intravenous glucose tolerance test in 6 obese client-owned cats before and after 12 weeks of twice-daily subcutaneous exenatide treatment. Insulin and glucose were measured immediately before and for 120 min following a 1 g/kg intravenous bolus of glucose.</p

Plasma insulin and glucose concentration in placebo treated cats.

<p>Plasma insulin and glucose concentration during an intravenous glucose tolerance test in 6 obese client-owned cats before and after 12 weeks of twice-daily subcutaneous placebo treatment. Insulin and glucose were measured immediately before and for 120 min following a 1 g/kg intravenous bolus of glucose.</p

Hormone, glucose and body composition analyses before and after 12 weeks of either exenatide or placebo treatment.

<p>Hormone, glucose and body composition analyses before and after 12 weeks of either exenatide or placebo treatment.</p