Comparison of the Impact of Insulin Degludec U100 and Insulin Glargine U300 on Glycemic Variability and Oxidative Stress in Insulin-Naive Patients With Type 2 Diabetes Mellitus: Pilot Study for a Randomized Trial

Pavle Vrebalov Cindro, Mladen Krnić, Darko Modun, Jonatan Vuković, Tina Tičinović Kurir, Goran Kardum, Doris Rušić, Ana Šešelja Perišin, Josipa Bukić, Pavle Vrebalov Cindro, Mladen Krnić, Darko Modun, Jonatan Vuković, Tina Tičinović Kurir, Goran Kardum, Doris Rušić, Ana Šešelja Perišin, Josipa Bukić

Abstract

Background: There is an ongoing discussion about possible differences between insulin degludec (IDeg-100) and glargine U300 (IGlar-300). There is little data and head-to-head comparison of IDeg-100 and IGlar-300 regarding their simultaneous impact on glycemic variability and oxidative stress in patients with type 2 diabetes mellitus (T2DM).

Objective: In our randomized, open-label, crossover study, we compared the impact of IDeg-100 and IGlar-300 on glycemic variability and oxidative stress in insulin-naive patients with T2DM.

Methods: We recruited a total of 25 adult patients with T2DM (7 females) whose diabetes was uncontrolled (HbA1c ≥7.5%) on two or more oral glucose-lowering drugs; a total of 22 completed the study. Mean age was 57.3 (SD 6.99) years and duration of diabetes was 9.94 (SD 5.01) years. After the washout period, they were randomized alternately to first receive either IDeg-100 or IGlar-300 along with metformin. Each insulin was administered for 12 weeks and then switched. At the beginning and end of each phase, biochemical and oxidative stress parameters were analyzed. On 3 consecutive days prior to each control point, patients performed a 7-point self-monitoring of blood glucose profile. Oxidative stress was assessed by measuring thiol groups and hydroperoxides (determination of reactive oxygen metabolites test) in serum.

Results: IGlar-300 reduced mean glucose by 0.02-0.13 mmol/L, and IDeg-100 reduced glucose by 0.10-0.16 mmol/L, with no significant difference. The reduction of the coefficient of glucose variation also did not show a statistically significant difference. IGlar-300 increased thiols by 0.08 µmol/L and IDeg-100 increased thiols by 0.15 µmol/L, with no significant difference (P=.07) between them. IGlar-300 reduced hydroperoxides by 0.040 CARR U and IDeg-100 increased hydroperoxides by 0.034 CARR U, but the difference was not significant (P=.12).

Conclusions: The results of our study do not show a significant difference regarding glycemic variability between patients receiving either insulin IDeg-100 or IGlar-300, although IGlar-300 showed greater dispersion of data. No significant difference in oxidative stress was observed. In a larger study, doses of insulins should be higher to achieve significant impact on glycemic parameters and consequently on glycemic variability and oxidative stress.

Trial registration: ClinicalTrials.gov, NCT04692415; https://ichgcp.net/clinical-trials-registry/NCT04692415.

Keywords: RCT; clinical trial; control trial; diabetes; diabetic; glucose variability; glycaemic variability; glycemic variability; insulin; insulin degludec; insulin glargine U300; oxidative stress; pilot; type 2 diabetes mellitus; type two diabetes mellitus.

Conflict of interest statement

Conflicts of Interest: MK received honoraria from Sanofi, NovoNordisk, Eli Lilly, Abbott, MSD, Takeda, Novartis, Boehringer Ingelheim, Servier, Lifescan, and AstraZeneca as a speaker and for attendance at advisory boards. MK author has no conflicts of interest associated with this research.

TTK received honoraria from Sanofi, NovoNordisk, Eli Lilly, Abbott, MSD, Takeda, Novartis, Boehringer Ingelheim, Servier, Lifescan, and AstraZeneca as a speaker and for attendance at advisory boards. TTK author has no conflicts of interest associated with this research.

PVC received honoraria from Abbott, Teva, and Takeda as a speaker and a case presenter. PVC author has no conflicts of interest associated with this research.

JV, DM, GK, DR, ASP, and JB declare no conflicts of interest associated with this research.

©Pavle Vrebalov Cindro, Mladen Krnić, Darko Modun, Jonatan Vuković, Tina Tičinović Kurir, Goran Kardum, Doris Rušić, Ana Šešelja Perišin, Josipa Bukić. Originally published in JMIR Formative Research (https://formative.jmir.org), 08.07.2022.

Figures

Figure 1
Figure 1
The study protocol.
Figure 2
Figure 2
Mean glucose change, SD, and CV on the first, second, and third day. CV: coefficient of variation; IDeg-100: insulin degludec; IGlar-300: insulin glargine U300. A) Mean glucose change on the first day. B) SD of glucose change on the first day. C) CV of glucose change on the first day. D) Mean glucose change on the second day. E) SD of glucose change on the second day. F) CV of glucose change on the second day. G) Mean glucose change on the third day. H) SD of glucose change on the third day. I) CV of glucose change on the third day.
Figure 3
Figure 3
Changes in plasma thiols and hydroperoxides. GSH: glutathione; IDeg-100: insulin degludec; IGlar-300: insulin glargine U300. A) Changes in plasma thiols. B) Changes in plasma hydroperoxides.

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