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

J Vet Intern Med. 2022 Jul;36(4):1211-1219. doi: 10.1111/jvim.16449. Epub 2022 May 27.


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.

Keywords: FcRn; IgG; adherence; compliance; continuous glucose monitoring; once-weekly insulin.

Publication types

  • Clinical Trial, Veterinary

MeSH terms

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


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