Efficacy and Safety of Porcine Insulin Zinc Suspension (IZS-P) for Reducing Hyperglycemia and Associated Clinical Signs in Cats with Diabetes Mellitus
An open, unmasked study was conducted to provide substantial evidence of the clinical effectiveness and safety of porcine insulin zinc suspension (IZS-P, Vetsulin®) for reducing hyperglycemia and its associated signs in cats with diabetes mellitus. The study was conducted in the US in accordance with the current FDA, CVM and VICH Guidance on Good Clinical Practice.
Cats were enrolled based on elevated fasting blood glucose (>250 mg/dL on two occasions) with concurrent glycosuria and clinical signs of diabetes mellitus. Cats that met specified criteria on prior treatment or with coexisting primary diseases were excluded. A baseline blood glucose curve (Day 0) was completed (Accu-Chek® Advantage®) and IZS-P therapy (approximately 1 to 2 IU per subcutaneous injection q 12 h) initiated. Glucose curves and clinical signs were re-evaluated on Days 7, 14, 30, 60 and 180 and the dose was adjusted accordingly. Overall response to treatment in each cat was recorded on a visual analogue scale (VAS). Additional examinations to assess the long-term safety were carried out at 90, 120 and 150 days. Complete blood count (CBC) and serum chemistry were performed during the course of the study and urinalysis prior to enrollment.
Mean VAS score decreased from 93.8 mm on Day 0 to 31.2 mm and 25.0 mm on Days 60 and 180 , respectively (p<0.001 both days). This was mirrored by a substantial reduction in polyuria, polydipsia and polyphagia. Mean blood glucose decreased from 394.1 mg/dL on Day 0 (n=77) to 216.7 mg/dL (n=76) and 219.5 mg/dL (n=73) on Days 60 and 180, respectively (p<0.001 both days). Mean glucose nadir decreased from 343.3 mg/dL on Day 0 to 145.7 mg/dL and 155.9 mg/dL on Days 60 and Day 180, respectively (p<0.001 both days). Blood glucose was <300 mg/dL in 5.2%, 75.0% and 71.2% of the cats and blood glucose nadir <200 mg/dL in 0%, 72.4% and 69.9% of the cats on Days 0, 60 and 180, respectively. Mean fructosamine concentration decreased from 604.3 µmol/L on Day 0 to 451.3 µmol/L and 448.4 µmol/L on Days 60 and 180, respectively (p<0.001 both days). Diabetes remission occurred in four cats. Less than 3% (2/77) of the cats failed to respond to treatment.
Hypoglycemia (blood glucose concentration <50 mg/dl) was reported as an adverse event associated with clinical signs (lethargy, diarrhea, vomiting, and/or hypothermia) in 13/78 cats and without clinical signs in 17/78 cats, 11 of the latter received oral glucose replacement. Five cats experienced more than one hypoglycemic event. Polyneuropathy was documented in 5.1% (4/78) of the cats. Two injection site reactions were reported (mild bruising at the injection site, mildly thickened subcutis).
These results confirm that IZS-P is effective and safe for reducing hyperglycemia and its associated clinical signs in cats with diabetes mellitus.