The effect of liraglutide and sitagliptin on oxidative stress in persons with type 2 diabetes.

Sivalingam S, Larsen EL, van Raalte DH, Muskiet MHA, Smits MM, Tonneijck L, Joles JA, von Scholten BJ, Zobel EH, Persson F, Henriksen T, Diaz LJ, Hansen TW, Poulsen HE, Rossing P

Scientific reports19 May 2021Cited by 14 (Europe PMC)

PMID34012064PMCIDPMC8134438DOI10.1038/s41598-021-90191-wPepBankPUB-34012064

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Summary

Glucagon-like peptide 1 receptor agonists have shown cardioprotective effects which have been suggested to be mediated through inhibition of oxidative stress. We investigated the effect of treatment with a glucagon-like peptide 1 receptor agonist (liraglutide) on oxidative stress measured as urinary nucleic acid oxidation in persons with type 2 diabetes. Post-hoc analysis of two independent, randomised, placebo-controlled and double-blinded clinical trials. In a cross-over study where persons with type 2 diabetes and microalbuminuria (LIRALBU, n = 32) received liraglutide (1.8 mg/day) or placebo for 12 weeks in random order, separated by 4 weeks of wash-out. In a parallel-grouped study where obese persons with type 2 diabetes (SAFEGUARD, n = 56) received liraglutide (1.8 mg/day), sitagliptin (100 mg/day) or placebo for 12 weeks. Endpoints were changes in the urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)) and RNA oxidation [8-oxo-7,8-dihydroguanosine (8-oxoGuo)]. In LIRALBU, we observed no significant differences between treatment periods in urinary excretion of 8-oxodG [0.028 (standard error (SE): 0.17] nmol/mmol creatinine, p = 0.87) or of 8-oxoGuo [0.12 (0.12) nmol/mmol creatinine, p = 0.31]. In SAFEGUARD, excretion of 8-oxodG was not changed in the liraglutide group [2.8 (- 8.51; 15.49) %, p = 0.62] but a significant decline was demonstrated in the placebo group [12.6 (- 21.3; 3.1) %, p = 0.02], resulting in a relative increase in the liraglutide group compared to placebo (0.16 nmol/mmol creatinine, SE 0.07, p = 0.02). Treatment with sitagliptin compared to placebo demonstrated no significant difference (0.07 (0.07) nmol/mmol creatinine, p = 0.34). Nor were any significant differences for urinary excretion of 8-oxoGuo liraglutide vs placebo [0.09 (SE: 0.07) nmol/mmol creatinine, p = 0.19] or sitagliptin vs placebo [0.07 (SE: 0.07) nmol/mmol creatinine, p = 0.35] observed. This post-hoc analysis could not demonstrate a beneficial effect of 12 weeks of treatment with liraglutide or sitagliptin on oxidatively generated modifications of nucleic acid in persons with type 2 diabetes.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

5 results from studies that gave the peptide. 5 results from people.

01HumanRandomized controlled trialEfficacy outcome
In persons with type 2 diabetes and microalbuminuria, liraglutide did not significantly change urinary DNA oxidation (8-oxodG) compared with placebo in a cross-over study.
In plain wordsIn people with type 2 diabetes and protein in the urine, liraglutide did not change a urine marker of DNA damage compared with placebo.
Peptide
Liraglutide
Outcome
No significant changeUrinary 8-oxodG in LIRALBU
Study
n = 32
Comparator
Placebo
Outcome group
Aging markers · Metabolic and weight
Studied dose
1.8 mg/day · 12 weeksAs given in this study (human).
Source sentences
Summary
In LIRALBU, we observed no significant differences between treatment periods in urinary excretion of 8-oxodG [0.028 (standard error (SE): 0.17] nmol/mmol creatinine, p = 0.87)
1 context sentence(design, population, supporting numbers)
Summary · context
In a cross-over study where persons with type 2 diabetes and microalbuminuria (LIRALBU, n = 32) received liraglutide (1.8 mg/day) or placebo for 12 weeks in random order, separated by 4 weeks of wash-out.
Show in the study text Report a problemFND-3401206401
02HumanRandomized controlled trialEfficacy outcome
In persons with type 2 diabetes and microalbuminuria, liraglutide did not significantly change urinary RNA oxidation (8-oxoGuo) compared with placebo in a cross-over study.
In plain wordsIn people with type 2 diabetes and protein in the urine, liraglutide did not change a urine marker of RNA damage compared with placebo.
Peptide
Liraglutide
Outcome
No significant changeUrinary 8-oxoGuo in LIRALBU
Study
n = 32
Comparator
Placebo
Outcome group
Aging markers · Metabolic and weight
Studied dose
1.8 mg/day · 12 weeksAs given in this study (human).
Source sentences
Summary
or of 8-oxoGuo [0.12 (0.12) nmol/mmol creatinine, p = 0.31]
1 context sentence(design, population, supporting numbers)
Summary · context
In a cross-over study where persons with type 2 diabetes and microalbuminuria (LIRALBU, n = 32) received liraglutide (1.8 mg/day) or placebo for 12 weeks in random order, separated by 4 weeks of wash-out.
Show in the study text Report a problemFND-3401206402
03HumanRandomized controlled trialEfficacy outcome
In obese persons with type 2 diabetes, urinary 8-oxodG showed a relative increase with liraglutide compared with placebo, because it declined in the placebo group.
In plain wordsIn obese people with type 2 diabetes, a urine marker of DNA damage was relatively higher with liraglutide than placebo, because it fell on placebo.
Peptide
Liraglutide
Outcome
IncreaseUrinary 8-oxodG in SAFEGUARD, liraglutide vs placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Aging markers · Metabolic and weight
Studied dose
1.8 mg/day · 12 weeksAs given in this study (human).
Source sentences
Summary
but a significant decline was demonstrated in the placebo group [12.6 (- 21.3; 3.1) %, p = 0.02], resulting in a relative increase in the liraglutide group compared to placebo (0.16 nmol/mmol creatinine, SE 0.07, p = 0.02).
1 context sentence(design, population, supporting numbers)
Summary · context
In a parallel-grouped study where obese persons with type 2 diabetes (SAFEGUARD, n = 56) received liraglutide (1.8 mg/day), sitagliptin (100 mg/day) or placebo for 12 weeks.
Show in the study text Report a problemFND-3401206403
04HumanRandomized controlled trialEfficacy outcome
In obese persons with type 2 diabetes, urinary 8-oxodG excretion was not changed in the liraglutide group.
In plain wordsIn obese people with type 2 diabetes, a urine marker of DNA damage did not change in the liraglutide group.
Peptide
Liraglutide
Outcome
No significant changeUrinary 8-oxodG change within the liraglutide group in SAFEGUARD
Study
n: not reported in source
Comparator
Baseline
Outcome group
Aging markers · Metabolic and weight
Studied dose
1.8 mg/day · 12 weeksAs given in this study (human).
Source sentences
Summary
In SAFEGUARD, excretion of 8-oxodG was not changed in the liraglutide group [2.8 (- 8.51; 15.49) %, p = 0.62]
1 context sentence(design, population, supporting numbers)
Summary · context
In a parallel-grouped study where obese persons with type 2 diabetes (SAFEGUARD, n = 56) received liraglutide (1.8 mg/day), sitagliptin (100 mg/day) or placebo for 12 weeks.
Show in the study text Report a problemFND-3401206404
05HumanRandomized controlled trialEfficacy outcome
In obese persons with type 2 diabetes, urinary RNA oxidation (8-oxoGuo) did not differ significantly between liraglutide and placebo.
In plain wordsIn obese people with type 2 diabetes, a urine marker of RNA damage did not differ between liraglutide and placebo.
Peptide
Liraglutide
Outcome
No significant changeUrinary 8-oxoGuo in SAFEGUARD, liraglutide vs placebo
Study
n: not reported in source
Comparator
Placebo
Outcome group
Aging markers · Metabolic and weight
Studied dose
1.8 mg/day · 12 weeksAs given in this study (human).
Source sentences
Summary
Nor were any significant differences for urinary excretion of 8-oxoGuo liraglutide vs placebo [0.09 (SE: 0.07) nmol/mmol creatinine, p = 0.19]
1 context sentence(design, population, supporting numbers)
Summary · context
In a parallel-grouped study where obese persons with type 2 diabetes (SAFEGUARD, n = 56) received liraglutide (1.8 mg/day), sitagliptin (100 mg/day) or placebo for 12 weeks.
Show in the study text Report a problemFND-3401206405

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
12 Oct 2026, 11:11 UTC
Study results updated
Version 1
9 Oct 2026, 03:05 UTC
First added · source update from Europe PMC

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