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. 2025 May 15:16:1438318.
doi: 10.3389/fphar.2025.1438318. eCollection 2025.

Comparative effectiveness of semaglutide versus liraglutide, dulaglutide or tirzepatide: a systematic review and meta-analysis

Mohammad Amin Karimi #  1 , Mohammad Sadra Gholami Chahkand #  2 , Parisa Alsadat Dadkhah  3 , Farzad Sheikhzadeh  4 , Shayan Yaghoubi  5 , Fatemeh Esmaeilpour Moallem  2 , Mitra Sadat Deyhimi  3 , Melika Arab Bafrani  6 , Mehregan Shahrokhi  7 , Amir Nasrollahizadeh  8
Affiliations

Comparative effectiveness of semaglutide versus liraglutide, dulaglutide or tirzepatide: a systematic review and meta-analysis

Mohammad Amin Karimi et al. Front Pharmacol. .

Abstract

Background: This study seeks to compare the effectiveness of Semaglutide compared to Liraglutide, Dulaglutide, or Tirzepatide. Additionally, it aims to investigate the implications of transitioning from Dulaglutide or Liraglutide to Semaglutide.

Methods: We searched PubMed, Scopus, Cochrane Library, Google Scholar, and Web of Science (ClinicalTrials.gov for unpublished records) from their inception to 5 February 2025, including observational cohort studies and randomized controlled trials. Analyses were conducted using Review Manager (RevMan) version 5.4.1 and STATA 17.

Results: The meta-analysis comprised 16 studies and 5,997 patients. Semaglutide significantly reduced hemoglobin A1c (HbA1c) levels compared to Liraglutide (0.56; 95% CI: 0.19-0.94; p < 0.001). However, no significant differences were observed between Semaglutide and Liraglutide in terms of fasting blood sugar (FBS), body mass index (BMI), and weight change. In comparison to Dulaglutide, Semaglutide displayed superior efficacy in reducing HbA1c levels (3.72; 95% CI: 0.02-7.41; p = 0.05) and FBS (2.66; 95% CI: 0.26-5.07; p = 0.03). However, no significant differences were found in weight and BMI change. Tirzepatide exhibited a notable advantage over Semaglutide in reducing HbA1c levels (-0.45; 95% CI: -0.88 to -0.02; p = 0.04). However, no clear superiority was observed for weight and FBS change. Transitions from Liraglutide to Semaglutide did not significantly impact HbA1c levels. However, weight loss (2.48; 95% CI: 0.45-4.51; p = 0.02) and reduced FBS levels (10.76; 95% CI: 0.55-20; p = 0.04) were observed. Transitioning from Dulaglutide to Semaglutide did not significantly affect HbA1c levels and weight change.

Conclusion: While the precise source of heterogeneity remains elusive across most studies, analyses consistently demonstrate Semaglutide's superior efficacy compared to Liraglutide in reducing both HbA1c levels and weight. Moreover, it presents advantages over Dulaglutide, specifically in lowering FBS levels. However, Tirzepatide surpasses Semaglutide in its efficacy for reducing HbA1c levels.

Keywords: GLP-1 (Glucagon-Like Peptide 1); HbA1c; dulaglutide; liraglutide; randomized controlled trials; semaglutide; tirzepatide; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
PRISMA flowchart illustrating the selection process of studies included in the systematic review and meta-analysis.
FIGURE 2
FIGURE 2
The impact of Semaglutide versus Dulaglutide on HbA1c changes.
FIGURE 3
FIGURE 3
The impact of Semaglutide versus Dulaglutide on Weight changes.
FIGURE 4
FIGURE 4
The impact of Semaglutide and Dulaglutide on FBS levels.
FIGURE 5
FIGURE 5
The effect of Semaglutide and Dulaglutide on BMI alterations.
FIGURE 6
FIGURE 6
Comparison of HbA1c changes between Semaglutide and Liraglutide.
FIGURE 7
FIGURE 7
The impact of Semaglutide versus Liraglutide on weight changes.
FIGURE 8
FIGURE 8
The effect of Semaglutide and Liraglutide on FBS.
FIGURE 9
FIGURE 9
The effect of Semaglutide and Liraglutide on BMI.
FIGURE 10
FIGURE 10
Impact of Semaglutide and Tirzepatide on HbA1c changes.
FIGURE 11
FIGURE 11
Effect of Semaglutide and Tirzepatide on weight changes.
FIGURE 12
FIGURE 12
Impact of semaglutide and tirzepatide on FBS alterations.
FIGURE 13
FIGURE 13
Effect of transitioning treatment from Liraglutide to Semaglutide on HbA1c alterations.
FIGURE 14
FIGURE 14
Impact of switching treatment from Liraglutide to Semaglutide on weight changes.
FIGURE 15
FIGURE 15
Impact of switching treatment from Liraglutide to Semaglutide on FBS changes.
FIGURE 16
FIGURE 16
Effect of transitioning treatment from Dulaglutide to Semaglutide on HbA1c changes.
FIGURE 17
FIGURE 17
Effect of transitioning treatment from dulaglutide to semaglutide on weight changes.
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