Glycemic variability in newly diagnosed diabetic cats treated with the glucagon‐like peptide‐1 analogue exenatide extended release

Journal of Feline Medicine and Surgery

et al. 2021

Self Cite

Objectives The study aimed to evaluate the efficacy and safety of insulin glargine 300 U/ml (IGla-U300) in cats with variable duration of diabetes mellitus (DM). Methods Thirteen client-owned cats with DM completed a prospective clinical trial. Four cats were highly suspected of hypersomatotropism and excluded from the insulin efficacy evaluation. All cats were treated with IGla-U300 SC at a starting dosage of 0.5 U/kg q12h and fed with a low carbohydrate diet. Cats were monitored for 8 weeks with a once-weekly at-home 16 h blood glucose curve (BGC) and a questionnaire evaluating the presence of DM-related clinical signs. In-clinic evaluations, including serum fructosamine measurement, were scheduled within 3 days of the first, third, sixth and eighth BGC. Glycemic variability was assessed by calculating the SD of each BGC. Results Excluding four cats suspected of hypersomatotropism, at the time of the eighth BGC, improved or absent polyuria, polydipsia, polyphagia, weight loss, lethargy and improved or normal general demeanor were reported in 8/9 (88%), 8/9 (88%), 7/9 (77%), 7/9 (77%), 7/9 (77%) and 8/9 (88%) cats, respectively. Two cats achieved remission after 29 and 53 days. Another two cats went into remission after the end of the study (days 82 and 96). All cats that achieved remission were newly diagnosed diabetics. Median (range) serum fructosamine concentration significantly decreased when comparing the time of enrollment (604 [457–683] µmol/l) with the eighth week of treatment (366 [220–738] µmol/l) ( P = 0.02). In all 13 cats, biochemical hypoglycemia (blood glucose <60 mg/dl; <3.3 mmol/l) was detected in 13/104 (12.5%) BGCs, while clinical signs suggesting hypoglycemic episodes were not reported. Glycemic variability was significantly lower at the fifth BGC when comparing cats that achieved remission with cats that did not achieve remission ( P = 0.02). Conclusions and relevance IGla-U300 seems effective and safe for the treatment of feline diabetes, but more long- term and comparative clinical trials are needed.

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Insulin glargine 300 U/ml for the treatment of feline diabetes mellitus

Linari

Fleeman

Journal of Feline Medicine and Surgery

et al. 2021

Self Cite

“…This difference in variability was observed in the 1st week after the study insulin was administered, even while mean IG was increasing. Decreased glucose variability might be important, considering recent evidence that decreased glucose variability in cats is associated with increased frequency of diabetic remission 16 . Whether decreased glucose variability was the cause or effect of normalizing glycemia was difficult to discern in that study, but the sequence of events in the cats presented here suggests that normalizing glycemia was not the cause of decreasing GVP.…”

Section: Discussionmentioning

confidence: 62%

An ultra‐long‐acting recombinant insulin for the treatment of diabetes mellitus in cats

Veterinary Internal Medicne

Hulsebosch

Pires

et al. 2021

Background Treatment of diabetes mellitus (DM) in cats typically requires insulin injections q12h‐q24h, posing a major compliance barrier for caregivers. Novel treatments enabling decreased injection frequency while maintaining safety are highly desirable. Insulin fused with feline immunoglobulin fragment crystallizable (Fc) has an ultra‐long plasma half‐life because it recycles through cells where it is protected from proteolysis. Hypothesis Glycemic control can be achieved in diabetic cats with a recombinant fusion protein of a synthetic insulin and feline Fc (AKS‐267c) administered SC weekly. Animals Five cats with spontaneous DM. Methods Cats previously controlled using insulin glargine q12h were transitioned to once‐weekly injection of AKS‐267c. The dose of AKS‐267c was titrated weekly for 7 weeks based on continuous glucose monitoring. Clinical signs, body weight, fructosamine concentrations, and mean interstitial glucose concentrations (IG) were compared between baseline (week 0, on insulin glargine) and the last week of treatment. Data were assessed for normality and compared using parametric or nonparametric paired tests (as appropriate). Results After 7 weeks of once‐weekly injections, compared to baseline, there were no significant changes in clinical signs, body weight (median [range] gain, 0.1 kg [−0.1 to +0.7]; P = .5), fructosamine (−60 mmol/L [−338 to +206]; P = .6), and mean IG concentrations (change = −153 mmol/L [−179 to +29]; P = .3), and no adverse reactions were reported. Conclusion Successful control of clinical signs and maintenance of glycemia was achieved with this once‐weekly novel insulin treatment. The efficacy and safety of this novel formulation should be further assessed in a large clinical trial.

“…Increased glycaemic variability appears to be more common in cats that do not go on to achieve diabetic remission, and in those with concurrent diseases (Krämer et al . 2020a,b). Insulin‐induced hypoglycaemia also seemed to be more easily avoided in dogs than in cats by careful attention to management practises and concurrent medical conditions (Whitley et al .…”

Section: General Principles Of Insulin Therapymentioning

confidence: 99%

One hundred years of insulin: Is it time for smart?

J of Small Animal Practice

Fleeman

2022

Smarter understanding of diabetes pathophysiology and pharmacology of insulin therapy can lead to better clinical outcomes. Rather than looking for an insulin formulation that is considered “best” for a general population, it could be appropriate to seek the “smart” insulin choice, tailored to the specific clinical situation. Different treatment goals should be considered, with pros and cons to each. Ideally, insulin therapy in most diabetic dogs should mimic a “basal‐bolus” pattern. The “intermediate”‐acting insulin formulations might provide better “bolus” treatment in dogs than the rapid‐acting formulations used in people. In patients with some residual beta cell function such as many diabetic cats, administering only a “basal” insulin might lead to complete normalisation of blood glucose concentrations. Insulin suspensions (neutral protamine Hagedorn, neutral protamine Hagedorn/regular mixes, lente and protamine zinc insulin) as well as insulin glargine U100 and detemir are “intermediate”‐acting formulations that are administered twice daily. For a formulation to be an effective and safe “basal” insulin, its action should be roughly the same every hour of the day. Currently, only insulin glargine U300 and insulin degludec meet this standard in dogs, whereas in cats, insulin glargine U300 is the closest option.