PMID- 35802405
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220905
IS  - 2561-326X (Electronic)
IS  - 2561-326X (Linking)
VI  - 6
IP  - 7
DP  - 2022 Jul 8
TI  - 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.
PG  - e35655
LID - 10.2196/35655 [doi]
LID - e35655
AB  - 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 (HbA(1c) >/=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 
      micromol/L and IDeg-100 increased thiols by 0.15 micromol/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://clinicaltrials.gov/ct2/show/NCT04692415.
CI  - (c)Pavle Vrebalov Cindro, Mladen Krnic, Darko Modun, Jonatan Vukovic, Tina 
      Ticinovic Kurir, Goran Kardum, Doris Rusic, Ana Seselja Perisin, Josipa Bukic. 
      Originally published in JMIR Formative Research (https://formative.jmir.org), 
      08.07.2022.
FAU - Vrebalov Cindro, Pavle
AU  - Vrebalov Cindro P
AUID- ORCID: 0000-0002-1334-2160
AD  - Department of Gastroenterology, University Hospital Split, Split, Croatia.
FAU - Krnic, Mladen
AU  - Krnic M
AUID- ORCID: 0000-0002-3676-1608
AD  - Department of Endocrinology, University Hospital Split, Split, Croatia.
AD  - Department of Pathophysiology, School of Medicine, University of Split, Split, 
      Croatia.
FAU - Modun, Darko
AU  - Modun D
AUID- ORCID: 0000-0001-9508-9383
AD  - Department of Pharmacy, School of Medicine, University of Split, Split, Croatia.
FAU - Vukovic, Jonatan
AU  - Vukovic J
AUID- ORCID: 0000-0002-7878-7988
AD  - Department of Gastroenterology, University Hospital Split, Split, Croatia.
FAU - Ticinovic Kurir, Tina
AU  - Ticinovic Kurir T
AUID- ORCID: 0000-0001-5975-5393
AD  - Department of Endocrinology, University Hospital Split, Split, Croatia.
AD  - Department of Pathophysiology, School of Medicine, University of Split, Split, 
      Croatia.
FAU - Kardum, Goran
AU  - Kardum G
AUID- ORCID: 0000-0002-5766-361X
AD  - Department of Psychology, Faculty of Humanities and Social Sciences, University 
      of Split, Split, Croatia.
FAU - Rusic, Doris
AU  - Rusic D
AUID- ORCID: 0000-0002-7018-4947
AD  - Department of Pharmacy, School of Medicine, University of Split, Split, Croatia.
FAU - Seselja Perisin, Ana
AU  - Seselja Perisin A
AUID- ORCID: 0000-0001-7927-5311
AD  - Department of Pharmacy, School of Medicine, University of Split, Split, Croatia.
FAU - Bukic, Josipa
AU  - Bukic J
AUID- ORCID: 0000-0002-9316-5538
AD  - Department of Pharmacy, School of Medicine, University of Split, Split, Croatia.
LA  - eng
SI  - ClinicalTrials.gov/NCT04692415
PT  - Journal Article
DEP - 20220708
PL  - Canada
TA  - JMIR Form Res
JT  - JMIR formative research
JID - 101726394
PMC - PMC9308081
OTO - NOTNLM
OT  - RCT
OT  - clinical trial
OT  - control trial
OT  - diabetes
OT  - diabetic
OT  - glucose variability
OT  - glycaemic variability
OT  - glycemic variability
OT  - insulin
OT  - insulin degludec
OT  - insulin glargine U300
OT  - oxidative stress
OT  - pilot
OT  - type 2 diabetes mellitus
OT  - type two diabetes mellitus
COIS- 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.
EDAT- 2022/07/09 06:00
MHDA- 2022/07/09 06:01
PMCR- 2022/07/08
CRDT- 2022/07/08 11:53
PHST- 2021/12/12 00:00 [received]
PHST- 2022/06/01 00:00 [accepted]
PHST- 2022/05/30 00:00 [revised]
PHST- 2022/07/08 11:53 [entrez]
PHST- 2022/07/09 06:00 [pubmed]
PHST- 2022/07/09 06:01 [medline]
PHST- 2022/07/08 00:00 [pmc-release]
AID - v6i7e35655 [pii]
AID - 10.2196/35655 [doi]
PST - epublish
SO  - JMIR Form Res. 2022 Jul 8;6(7):e35655. doi: 10.2196/35655.