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. 2021 Sep;35(5):2131-2139.
doi: 10.1111/jvim.16178. Epub 2021 Jul 9.

Day-to-day variability of porcine lente, insulin glargine 300 U/mL and insulin degludec in diabetic dogs

Affiliations

Day-to-day variability of porcine lente, insulin glargine 300 U/mL and insulin degludec in diabetic dogs

Michelle Miller et al. J Vet Intern Med. 2021 Sep.

Abstract

Background: Day-to-day variability impacts safety of insulin therapy and the choice of monitoring strategies. Side-by-side comparisons of insulin formulations in diabetic dogs are scarce.

Hypothesis/objectives: Insulin glargine 300 U/mL (IGla300) and insulin degludec (IDeg) are associated with less day-to-day glucose variability compared to porcine lente (PL) in diabetic dogs.

Animals: Seven intact male purpose-bred beagles with toxin-induced diabetes.

Methods: In this repeated measured study, PL, IGla300 and IDeg were compared in 2 phases: once-daily (q24h) and twice-daily (q12h) administration. Interstitial glucose concentrations (IG) were measured continuously throughout the study. For each formulation, maximal q24h dose was determined using the same algorithm (while avoiding hypoglycemia) and then maintained for 72 hours. In phase 2, 70% of the maximal q24h dose was administered q12h and maintained for 5 days regardless of hypoglycemia. Coefficient of variation (CV) and glycemic variability percentage (GVP) were calculated to determine day-to-day and intraday variability, respectively.

Results: There was no difference in day-to-day variability between PL, IGla300, and IDeg in the q24h phase. In the q12h phase, day-to-day variability was higher (P = .01) for PL (CV = 42.6 ± 6.8%) compared to IGla300 and IDeg (CV = 30.1 ± 7.7%, 25.2 ± 7.0%, respectively). The GVP of PL was lower (P = .02) compared to IGla300. There was no difference between PL, IGla300 and IDeg in %time IG < 70 mg/dL.

Conclusions and clinical importance: Insulin degludec and IGla300 administered q12h were associated with lower day-to-day variability, which might be advantageous in minimizing monitoring requirements without increasing the risk of hypoglycemia.

Keywords: basal insulin; diabetes mellitus; glycemic variability; hypoglycemia.

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Conflict of interest statement

Authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Insulin dose changing protocol during phase 1, once‐daily insulin therapy. Insulin dose was escalated until further increases could not be made due to IG < 70 mg/dL
FIGURE 2
FIGURE 2
Scatter plot of mean interstitial glucose (IG) over 3 days of once‐daily insulin therapy consisting of porcine lente (PL), insulin glargine 300 U/mL (IGla300) and insulin degludec (IDeg) in 7 purpose bred dogs. Horizontal line represents the mean of the 7 dogs. The means of the 3 treatment groups were compared with repeated measured ANOVA. P ≤ .05 was considered significant
FIGURE 3
FIGURE 3
Scatter plot of mean coefficient of variation % (CV) over 3 days of once‐daily insulin therapy consisting of porcine lente (PL), insulin glargine 300 U/mL (IGla300) and insulin degludec (IDeg) in 7 purpose bred dogs. Horizontal line represents the mean CV of the 7 dogs. The means of the 3 treatment groups were compared with 1‐way repeated measured ANOVA. P ≤ .05 was considered significant
FIGURE 4
FIGURE 4
Scatter plot of mean interstitial glucose (IG) over 5 days of twice‐daily insulin therapy consisting of porcine lente (PL), insulin glargine 300 U/mL (IGla300) and insulin degludec (IDeg) in 7 purpose bred dogs. Horizontal line represents the mean of the 7 dogs. The means of the 3 treatment groups were compared with repeated measured ANOVA. P ≤ .05 was considered significant
FIGURE 5
FIGURE 5
Scatter plot of percent of time the interstitial glucose (IG) was less than 70 mg/dL over 5 days of twice‐daily insulin therapy, porcine lente (PL), insulin glargine 300 U/mL (IGla300) and insulin degludec (IDeg) in 7 purpose bred dogs. Horizontal line represents the mean percent time for the 7 dogs. Freidman test and Dunn's multiple comparison test were used to compare frequencies of hypoglycemic events. P ≤ .05 was considered significant. ns = not significant
FIGURE 6
FIGURE 6
Scatter plot of mean coefficient of variation % (CV) over 5 days of twice‐daily insulin therapy consisting of porcine lente (PL), insulin glargine 300 U/mL (IGla300) and insulin degludec (IDeg) in 7 purpose bred dogs. Horizontal line represents the mean CV of the 7 dogs. The means of the 3 treatment groups were compared with 1‐way repeated measured ANOVA. P ≤ .05 was considered significant
FIGURE 7
FIGURE 7
A‐G, Continuous interstitial glucose (IG) curve over a 24‐hour period with twice daily insulin therapy. Food and insulin were given at time 0 and 660 minutes. Each panel of 3 graphs represents 1 dog. For each dog (A‐G), upper panel = porcine lente (PL), middle panel = insulin glargine 300 U/mL (IGla300), and lower panel = insulin degludec (IDeg)
FIGURE 8
FIGURE 8
Scatter plot of the mean glycemic variability percentage (GVP) over the 5 days of twice‐daily insulin therapy consisting of porcine lente (PL), insulin glargine 300 U/mL (IGla300) and insulin degludec (IDeg) in 7 purpose bred dogs. Horizontal line represents the mean GVP of the 7 dogs. The means of the 3 treatment groups were compared with 1‐way repeated measured ANOVA. P ≤ .05 was considered significant

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