Endocrinol Metab.  2024 Feb;39(1):109-126. 10.3803/EnM.2023.1839.

Efficacy and Safety of Omarigliptin, a Novel Once-Weekly Dipeptidyl Peptidase-4 Inhibitor, in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

• Kamrul-Hasan A
• Alam MS
• Talukder SK
• Dutta D
• Selim S

• KMID: 2552803
• DOI: http://doi.org/10.3803/EnM.2023.1839

Abstract

Background
No recent meta-analysis has holistically analyzed and summarized the efficacy and safety of omarigliptin in type 2 diabetes mellitus (T2DM). We conducted a meta-analysis to address this knowledge gap.
Methods
Electronic databases were searched to identify randomized controlled trials (RCTs) that included patients with T2DM who received omarigliptin in the intervention arm. The control arm consisted of either a placebo (passive control group [PCG]) or an active comparator (active control group [ACG]). The primary outcome assessed was changes in hemoglobin A1c (HbA1c), while secondary outcomes included variations in glucose levels, achievement of glycemic targets, adverse events (AEs), and hypoglycemic events.
Results
From 332 initially screened articles, data from 16 RCTs involving 8,804 subjects were analyzed. Omarigliptin demonstrated superiority over placebo in reducing HbA1c levels (mean difference, –0.58%; 95% confidence interval, –0.75 to –0.40; P<0.00001; I²=91%). Additionally, omarigliptin outperformed placebo in lowering fasting plasma glucose, 2-hour postprandial glucose, and in the percentage of participants achieving HbA1c levels below 7.0% and 6.5%. The glycemic efficacy of omarigliptin was similar to that of the ACG across all measures. Although the omarigliptin group experienced a higher incidence of hypoglycemic events compared to the PCG, the overall AEs, serious AEs, hypoglycemia, and severe hypoglycemia were comparable between the omarigliptin and control groups (PCG and ACG).
Conclusion
Omarigliptin has a favorable glycemic efficacy and safety profile for managing T2DM.

Keyword

Omarigliptin; Meta-analysis; Diabetes mellitus, type 2; Glycated hemoglobin; Safety; Hypoglycemia

Figure

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  Fig. 1. Flowchart on study retrieval and inclusion in the meta-analysis. aReason 1, pharmacokinetic and pharmacodynamic studies; Reason 2, observational study; Reason 3, retrospective study.

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  Fig. 2. Risk of bias assessment. (A) Risk of bias summary: review authors’ judgements about each risk of bias item for each included study. (B) Risk of bias graph: review authors’ judgements about each risk of bias item presented as percentages across all included studies.

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  Fig. 3. Forest plot highlighting the change in hemoglobin A1c from baseline. (A) Omarigliptin vs. passive control group (PCG). (B) Omarigliptin vs. active control group (ACG). SD, standard deviation; IV, inverse variance; CI, confidence interval.

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  Fig. 4. Forest plot highlighting the change in fasting plasma glucose from baseline. (A) Omarigliptin vs. passive control group (PCG). (B) Omarigliptin vs. active control group (ACG). SD, standard deviation; IV, inverse variance; CI, confidence interval.

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  Fig. 5. Forest plot highlighting the change in 2-hour postprandial glucose (PPG) from baseline. Omarigliptin vs. passive control group (PCG). SD, standard deviation; IV, inverse variance; CI, confidence interval.

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  Fig. 6. Forest plot highlighting the proportion of the study subjects that achieved hemoglobin A1c <7.0%. (A) Omarigliptin vs. passive control group (PCG). (B) Omarigliptin vs. active control group (ACG). IV, inverse variance; CI, confidence interval.

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  Fig. 7. Forest plot highlighting the proportion of the study subjects that achieved hemoglobin A1c <6.5%. (A) Omarigliptin vs. passive control group (PCG). (B) Omarigliptin vs. active control group (ACG). IV, inverse variance; CI, confidence interval.

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  Fig. 8. Forest plot highlighting adverse events. (A) Omarigliptin vs. passive control group (PCG). (B) Omarigliptin vs. active control group (ACG). IV, inverse variance; CI, confidence interval.

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  Fig. 9. Forest plot highlighting serious adverse events. (A) Omarigliptin vs. passive control group (PCG). (B) Omarigliptin vs. active control group (ACG). IV, inverse variance; CI, confidence interval.

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  Fig. 10. Forest plot highlighting events of hypoglycemia. (A) Omarigliptin vs. passive control group (PCG). (B) Omarigliptin vs. active control group (ACG). IV, inverse variance; CI, confidence interval.

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  Fig. 11. Forest plot highlighting events of severe hypoglycemia. (A) Omarigliptin vs. passive control group (PCG). (B) Omarigliptin vs. active control group (ACG). IV, inverse variance; CI, confidence interval.

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  Fig. 12. Forest plot highlighting changes in body weight from baseline. (A) Omarigliptin vs. passive control group (PCG). (B) Omarigliptin vs. active control group (ACG). SD, standard deviation; IV, inverse variance; CI, confidence interval.

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  Fig. 13. Forest plot highlighting changes in estimated glomerular filtration rate from baseline. (A) Omarigliptin vs. passive control group (PCG). (B) Omarigliptin vs. active control group (ACG). SD, standard deviation; IV, inverse variance; CI, confidence interval.

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  Fig. 14. Forest plot highlighting the changes in (A) serum amylase and (B) serum lipase from baseline. Omarigliptin vs. passive control group (PCG). SD, standard deviation; IV, inverse variance; CI, confidence interval.

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