Ultra-long-acting recombinant insulin for the treatment of diabetes mellitus in dogs.

Abstract

BACKGROUND:

For the treatment of diabetes mellitus (DM) in dogs, novel insulins with decreased injection frequency while maintaining safety and efficacy are desirable. Insulin fused with immunoglobulin-fragment-crystallizable (Fc) has an ultra-long plasma half-life because it recycles through cells, protected from proteolysis.

HYPOTHESIS:

Glycemic control can be achieved in diabetic dogs with a recombinant fusion protein of a synthetic insulin and canine Fc (AKS-218d) administered subcutaneously once-weekly.

ANIMALS:

Five client-owned dogs with naturally occurring DM.

METHODS:

Prospective clinical trial in dogs with DM that were recruited from the UC Davis Veterinary Teaching Hospital and local veterinary clinics. Dogs previously controlled using intermediate-acting insulin q12h were transitioned to once-weekly injections of a preliminary construct identified as AKS-218d. The dose of AKS-218d was titrated weekly for 8 weeks based on clinical response and continuous interstitial glucose monitoring. Clinical signs, body weight, serum fructosamine concentrations, and mean interstitial glucose concentrations (IG) over the preceding week were compared between baseline (before AKS-218d) and during the last week of treatment. Data were compared using nonparametric paired tests.

RESULTS:

Once-weekly AKS-218d, compared to baseline twice-daily insulin therapy, resulted in no significant changes in clinical signs, median (range) body weight (+0.4 kg [-0.5-1.1]; P = .6), fructosamine concentration (-75 mmol/L [-215 to +126]; P = .4), or mean IG (+81 mg/dL [-282 to +144]; P = .8). No adverse reactions were reported.

CONCLUSION:

Control of clinical signs, body weight, and maintenance of glycemia was achieved with this once-weekly novel insulin construct in 4 of 5 dogs.

• Authors: Sean E Hulsebosch, Jully Pires, Michael J Bannasch, Thomas Lancaster, Andrea Delpero, Ramya Ragupathy, Sylaja Murikipudi, Todd Zion, Chen Gilor
• Journal: Journal of veterinary internal medicine (J Vet Intern Med) Vol. 36 Issue 4 Pg. 1211-1219 (Jul 2022) ISSN: 1939-1676 [Electronic] United States
• PMID: 35621084 (Publication Type: Clinical Trial, Veterinary, Journal Article)
• Copyright: © 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Insulin
• Insulin Glargine
• Fructosamine

Topics

• Animals
• Blood Glucose (metabolism)
• Blood Glucose Self-Monitoring (veterinary)
• Body Weight
• Diabetes Mellitus (drug therapy, veterinary)
• Diabetes Mellitus, Type 2 (veterinary)
• Dog Diseases
• Dogs
• Fructosamine
• Hospitals, Animal
• Hospitals, Teaching
• Hypoglycemic Agents (adverse effects, therapeutic use)
• Insulin (therapeutic use)
• Insulin Glargine (adverse effects)
• Prospective Studies