Krämer, AL Riederer A, Boretti F, et al. Glycemic variability in newly diagnosed diabetic cats treated with the glucagon-like peptide-1 analogue exenatide extended release. J Vet Intern Med. 2020.
Diabetes mellitus (DM) is a common illness of domestic cats. It most closely resembles type II (non-insulin dependent) DM in humans, however many cats that are diagnosed have experienced significant glucose toxicity and most have some requirement for insulin. Glycemic variability (GV) is a measure of glycemic excursions, including hyper and hypoglycemia and is a marker of glucose control and a predictor of diabetic complications in humans. Several systems have been developed to quantify GV, of which perhaps the simplest is standard deviation of blood glucose.
Exenatide extended release (EER) is a long acting incretin analogue that increases glucose mediated insulin secretion, decreases glucagon secretion, increases satiation, and increased Beta-cell mass. The once-weekly SQ administration of EER in cats has been investigated and shown to be safe, with potential beneficial effects on glycemic control and diabetic remission.
The purpose of this paper was to investigate the effects of EER on GV in cats also receiving insulin. It was designed as a retrospective trial evaluating blood glucose curves of cats from a previously performed prospective placebo controlled trial. This trial recruited cats with DM admitted from 2013 to 2015 with a new diagnosis. Cats with previous corticosteroid or insulin administration or concurrent disease were excluded, as well as if they had received insulin or other antidiabetic medication for >4 weeks prior. Cats were stratified randomly into groups to receive either EER or placebo. All cats were also treated with insulin glargine and a low carbohydrate diet and doses adjusted based on weekly glucose curves. Curves were performed on capillary blood glucose recorded every 2 hours for an 8-12 hour period.
Thirty cats were recruited and fifteen cats enrolled in each treatment group. There was no significant difference between groups with respect to age, sex, weight, breed, previous ketoacidosis or previous treatments.
Data on these glucose curves were retrospectively evaluated. Mean and standard deviation BGs for each curve were calculated. There were compared between treatment groups, and between cats achieving and not achieving remission. Differences were also compared between week 1 and later weeks. Glucose curves were excluded from analysis once cats achieved remission.
The median insulin dose administered during the course of the study did not differ between groups. Mean BGs were significantly lower in the EER group than the control group. The frequency of hypoglycemia did not differ between groups. SD (as a marker of GV) was significantly lower in the EER group than the placebo group at week 6 and 10. SD was also lower within the EER group at weeks 6, 10, and 16 compared to week 1. There was no difference between weeks in the placebo group.
There was no difference in rate of remission or time to remission between groups. Cats achieving remission had lower GV at several time points compared to baseline.
The authors conclude that the use of EER is able to reduce glycemic variability in cats compared to placebo.
This paper discusses a relevant topic, and does so in a relative novel way with the use of GV. One limitation to the paper is the relative lack of previous studies on GV in cats, which makes interpretation of these results somewhat difficult. The study was also retrospective in nature and included a relatively small number of cats, however it was based on data from a previous prospective trial. Prospective, double-blinded placebo-controlled studies investigating the effects of EER on GV are needed in cats, as are studies investigating correlations between GV and overall diabetic control.
This paper successfully showed that GV is reduced in cats treated with EER and insulin glargine compared to insulin glargine alone. Further work is needed to determine the clinical relevance of this. (MRK)
Padrutt I, Lutz TA, Reusch CE, Zini E. Effects of the glucagon‐like peptide‐1 (GLP‐1) analogues exenatide, exenatide extended‐release, and of the dipeptidylpeptidase‐4 (DPP‐4) inhibitor sitagliptin on glucose metabolism in healthy cats. Res Vet Sci. 2015; 99: 23‐ 29.