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

Abstract

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.

Fig 1. Plasma insulin and glucose concentration in exenatide treated cats.

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.

Fig 2. Plasma insulin and glucose concentration in placebo treated cats.

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.

Fig 3. Individual differences in plasma insulin and glucose levels 120 minutes after a glucose bolus.

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.

Fig 4. Fasting plasma glucagon concentration.

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.

Fig 5. Body weight before, during and after the study period.

Body weight of 12 obese client-owned cats before and after 12 weeks of treatment with either exenatide (broken lines, n = 6) or placebo (solid line, n = 6). Two cats (one in each group) were withdrawn after 4 and 8 weeks respectively.