Pasireotide for the Medical Management of Feline Hypersomatotropism

Abstract

BackgroundFeline hypersomatotropism (HST) is a cause of diabetes mellitus in cats. Pasireotide is a novel multireceptor ligand somatostatin analog that improves biochemical control of humans with HST.Hypothesis/ObjectivesPasireotide improves biochemical control of HST and diabetes mellitus in cats.AnimalsHypersomatotropism was diagnosed in diabetic cats with serum insulin‐like growth factor‐1 (IGF‐1) concentration >1,000 ng/mL by radioimmunoassay and pituitary enlargement.MethodsInsulin‐like growth factor 1 was measured and glycemic control assessed using a 12‐hour blood glucose curve on days 1 and 5. On days 2, 3, and 4, cats received 0.03 mg/kg pasireotide SC q12h. IGF‐1, insulin dose, and estimated insulin sensitivity (product of the area under the blood glucose curve [BGC] and insulin dose) were compared pre‐ and post treatment. Paired t‐tests or Wilcoxon signed rank tests were employed for comparison where appropriate; a linear mixed model was created to compare BGC results.ResultsInsulin‐like growth factor 1 decreased in all 12 cats that completed the study (median [range] day 1: 2,000 ng/mL [1,051–2,000] and day 5: 1,105 ng/mL [380–1,727], P = .002, Wilcoxon signed rank test). Insulin dose was lower on day 5 than on day 1 (mean reduction 1.3 [0–2.7] units/kg/injection, P = .003, paired t‐test). The product of insulin dose and area under the BGC was lower on day 5 than day 1 (difference of means: 1,912; SD, 1523; u × mg/dL × hours, P = .001; paired t‐test). No clinically relevant adverse effects were encountered.ConclusionsShort‐acting pasireotide rapidly decreased IGF‐1 in cats with HST and insulin‐dependent diabetes. The decrease in IGF‐1 was associated with increased insulin sensitivity.

Serum N‐Terminal Type III Procollagen Propeptide: An Indicator of Growth Hormone Excess and Response to Treatment in Feline Hypersomatotropism

“…Not all HSDM cases were insulin‐resistant (if defined as an insulin requirement >1.5 IU/kg/injection on a q12h protocol) at the time of assessment. This observation is in agreement with recent literature that describes confirmed HSDM cases as having a wide range of insulin requirements, and demonstrating that insulin resistance does not necessarily need to be present for a diagnosis of HSDM to be made …”

“…This observation is in agreement with recent literature that describes confirmed HSDM cases as having a wide range of insulin requirements, and demonstrating that insulin resistance does not necessarily need to be present for a diagnosis of HSDM to be made. 1,3,31 The PIIINP testing could have different characteristics to offer as a screening test, which might enhance the value of current IGF-1 screening. Indeed, nonacromegalic diabetic cats can have increased IGF-1 concentrations, and newly diabetic acromegalic cats may have normal IGF-1 concentrations.…”

Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation

“…Octreotide and pasireotide exert this effect on glucose homeostasis in acromegalic cats by inhibiting growth hormone secretion from the pars distalis and lowering insulin‐like growth factor‐1 concentrations. These drugs differ in their relative affinity for different SST receptors, and pasireotide is emerging as the better treatment for acromegaly in the cat . It is also possible that SST analogs alter secretion of glucagon and insulin from alpha‐ and beta‐cells, when used as treatments for feline hypersomatotropism, but insulin secretion has not been measured in cats.…”

“…It is also possible that SST analogs alter secretion of glucagon and insulin from alpha‐ and beta‐cells, when used as treatments for feline hypersomatotropism, but insulin secretion has not been measured in cats. Major differences exist in the glucose and insulin abnormalities occurring in cats compared with horses, with low insulin concentrations relative to glucose concentrations detected in feline diabetes mellitus, compared to hyperinsulinemia in the horse. These species differences are important because the ability of octreotide to suppress insulin secretion may be advantageous when managing ID in horses.…”

“…These drugs differ in their relative affinity for different SST receptors, and pasireotide is emerging as the better treatment for acromegaly in the cat. 20 It is also possible that SST analogs alter secretion of glucagon and insulin from alpha-and beta-cells, when used as treatments for feline hypersomatotropism, but insulin secretion has not been measured in cats. Major differences exist in the glucose and insulin abnormalities occurring in cats compared with horses, with low insulin concentrations relative to glucose concentrations detected in feline diabetes mellitus, 20 compared to hyperinsulinemia in the horse.…”