Tegoprazan as First- and Second-Line Therapy for Eradication of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis

Abstract

Objective: To evaluate the efficacy and safety of tegoprazan (TPZ) compared to conventional proton pump inhibitors (PPIs) for Helicobacter pylori eradication as first- and second-line therapies.

Methods: Four databases were searched for randomized controlled trials (RCTs) and retrospective studies comparing TPZ- and PPI-based regimens for H. pylori eradication published until October 15, 2024. A random-effects model was used to calculate pooled odds ratio (OR) and 95% confidence interval (CI) based on intention-to-treat and per-protocol analyses. The PROSPERO registration number of the study is CRD42024622705.

Results: Nine studies (three RCTs and six retrospective studies) involving 5228 treatment-naïve patients were included. TPZ was non-inferior to PPIs as a first-line therapy (intention-to-treat: odds ratio [OR] 1.066, 95% confidence interval [CI] 0.929–1.224; per-protocol: OR 1.142, 95% CI: 0.967–1.349). Subgroup analyses showed no significant differences based on study design, therapeutic regimen, or treatment duration. In patients with clarithromycin-resistant strains confirmed by 23S rRNA sequencing, TPZ achieved a higher eradication rate (OR 4.961, 95% CI 1.024–24.030). TPZ was associated with significantly lower odds of abdominal discomfort compared to PPIs (OR 0.490, 95% CI 0.268–0.897). Regarding treatment duration, a 14-day regimen was linked to a lower risk of diarrhea, while a 7-day regimen was associated with a higher risk of abdominal pain. No significant differences were observed in second-line therapeutic outcomes.

Conclusions: TPZ represents a non-inferior alternative to PPIs for H. pylori eradication, with potential benefits in clarithromycin-resistant infections and favorable safety profiles. Future studies are warranted to assess higher dosages and address pharmacokinetic limitations.

Keywords

clarithromycin resistance / Helicobacter pylori / meta-analysis / proton pump inhibitors / tegoprazan

References

[1] Y. C. Chen, P. Malfertheiner, H. T. Yu, et al., “Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022,” Gastroenterology 166, no. 4 (2024): 605-619.

[2] Y. Usui, Y. Taniyama, M. Endo, et al., “Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer,” New England Journal of Medicine 388, no. 13 (2023): 1181-1190.

[3] E. A. Argueta, M. A. Alsamman, S. F. Moss, and E. M. C. D'Agata, “Impact of Antimicrobial Resistance Rates on Eradication of Helicobacter pylori in a US Population,” Gastroenterology 160, no. 6 (2021): 2181-2183.e1.

[4] B. J. Kim, H. Lee, Y. C. Lee, et al., “Ten-Day Concomitant, 10-Day Sequential, and 7-Day Triple Therapy as First-Line Treatment for Helicobacter pylori Infection: A Nationwide Randomized Trial in Korea,” Gut and Liver 13, no. 5 (2019): 531-540.

[5] D. A. Katzka and P. J. Kahrilas, “Potassium-Competitive Acid Blocker Suppression of Gastric Acid in Erosive Esophagitis: Is Stronger and Longer Better?,” Gastroenterology 164, no. 1 (2023): 14-15.

[6] E. Yang, S. C. Ji, I. J. Jang, and S. Lee, “Evaluation of CYP2C19-Mediated Pharmacokinetic Drug Interaction of Tegoprazan, Compared With Vonoprazan or Esomeprazole,” Clinical Pharmacokinetics 62, no. 4 (2023): 599-608.

[7] E. Yang, S. Kim, B. Kim, et al., “Night-Time Gastric Acid Suppression by Tegoprazan Compared to Vonoprazan or Esomeprazole,” British Journal of Clinical Pharmacology 88, no. 7 (2022): 3288-3296.

[8] W. D. Chey, F. Mégraud, L. Laine, L. J. López, B. J. Hunt, and C. W. Howden, “Vonoprazan Triple and Dual Therapy for Helicobacter pylori Infection in the United States and Europe: Randomized Clinical Trial,” Gastroenterology 163, no. 3 (2022): 608-619.

[9] K. Murakami, Y. Sakurai, M. Shiino, N. Funao, A. Nishimura, and M. Asaka, “Vonoprazan, A Novel Potassium-Competitive Acid Blocker, as a Component of First-Line and Second-Line Triple Therapy for Helicobacter pylori Eradication: A Phase III, Randomised, Double-Blind Study,” Gut 65, no. 9 (2016): 1439-1446.

[10] J. E. Kanu and J. Soldera, “Treatment of Helicobacter pylori With Potassium Competitive Acid Blockers: A Systematic Review and Meta-Analysis,” World Journal of Gastroenterology 30, no. 9 (2024): 1213-1223.

[11] J.-H. Cho, S.-Y. Jin, and S. Park, “Comparison of Tegoprazan and Proton Pump Inhibitors for First-Line Helicobacter pylori Eradication: A Systematic Review With Meta-Analysis,” Expert Review of Anti-Infective Therapy 23, no. 2-4 (2025): 227-233.

[12] D. M. Simadibrata, E. Lesmana, I. Damara, et al., “Tegoprazan-Containing Versus Proton Pump Inhibitor-Containing Therapy for First-Line Eradication of Helicobacter pylori: A Meta-Analysis of Randomized Controlled Trials,” JGH Open 9, no. 3 (2025): e70134, https://doi.org/10.1002/jgh3.70134.

[13] T. Jin, W. Wu, L. Zhang, H. Xuan, H. X. Zhang, and L. Zhong, “The Efficacy and Safety of Vonoprazan and Tegoprazan in Helicobacter pylori Eradication: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Trials,” Therapeutic Advances in Gastroenterology 18 (2025): 17562848251314801, https://doi.org/10.1177/17562848251314801.

[14] M. J. Page, J. E. McKenzie, P. M. Bossuyt, et al., “The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews,” BMJ 372 (2021): n71, https://doi.org/10.1136/bmj.n71.

[15] G. Guyatt, A. D. Oxman, E. A. Akl, et al., “GRADE Guidelines: 1. Introduction—GRADE Evidence Profiles and Summary of Findings Tables,” Journal of Clinical Epidemiology 64, no. 4 (2011): 383-394.

[16] Y. J. Choi, Y. C. Lee, J. M. Kim, et al., “Triple Therapy-Based on Tegoprazan, a New Potassium-Competitive Acid Blocker, for First-Line Treatment of Helicobacter pylori Infection: A Randomized, Double-Blind, Phase III, Clinical Trial,” Gut and Liver 16, no. 4 (2022): 535-546.

[17] J. S. Kim, W. Ko, J. W. Chung, and T. H. Kim, “Efficacy of Tegoprazan-Based Bismuth Quadruple Therapy Compared With Bismuth Quadruple Therapy for Helicobacter pylori Infection: A Randomized, Double-Blind, Active-Controlled Study,” Helicobacter 28, no. 3 (2023): e12977, https://doi.org/10.1111/hel.12977.

[18] Q. Z. Kong, I. A. Mirza, X. Q. Zhang, et al., “Fourteen-Day Tegoprazan-Amoxicillin Dual Therapy as the First-Line Treatment of Helicobacter pylori Infection (SHARE2301): A Multicenter, Noninferiority, Randomized Clinical Trial,” Helicobacter 29, no. 3 (2024): e13098, https://doi.org/10.1111/hel.13098.

[19] Y. S. Jung, S. Kim, H. Y. Kim, et al., “Efficacy and Tolerability of 14-Day Tegoprazan- Versus Rabeprazole-Based Triple Therapy for Eradication of Helicobacter pylori: A Real-World Evidence Study,” Gut and Liver 17, no. 5 (2023): 711-721.

[20] B. W. Jung, C. H. Park, and Y. S. Jung, “Efficacy and Safety of Tegoprazan- and Rabeprazole-Based Concomitant Therapies for Helicobacter pylori Infection: Real-World Evidence,” Journal of Gastroenterology and Hepatology 39, no. 11 (2024): 2409-2416.

[21] S. Kang, N.-H. Kim, S. Jeong, et al., “Comparison of Tegoprazan- and Lansoprazole-Based Fourteen-Day Triple Therapies as First-Line Treatments for Helicobacter pylori Eradication,” Korean Journal of Helicobacter and Upper Gastrointestinal Research 24, no. 2 (2024): 168-174.

[22] J. Y. Kim, S. Y. Lee, H. Kim, J. H. Kim, I. K. Sung, and H. S. Park, “Efficacy of Seven-Day Potassium-Competitive Acid Blocker-Based First-Line Helicobacter Pylori Eradication Therapy Administered With Bismuth,” Yonsei Medical Journal 62, no. 8 (2021): 708-716.

[23] C. H. Park, J. H. Park, and Y. S. Jung, “Comparative Efficacy of Tegoprazan vs Esomeprazole/Sodium Bicarbonate for the Treatment of Helicobacter pylori Infection,” Clinical and Translational Gastroenterology 14, no. 11 (2023): e00632, https://doi.org/10.14309/ctg.0000000000000632.

[24] M. J. Song, B. W. Jung, and C. H. Park, “Comprehensive Analysis of Factors Associated With Helicobacter pylori Eradication Therapy,” Korean Journal of Helicobacter and Upper Gastrointestinal Research 24, no. 2 (2024): 157-167. [in Korean].

[25] D. Y. Graham, H. Lu, and Y. Yamaoka, “A Report Card to Grade Helicobacter pylori Therapy,” Helicobacter 12, no. 4 (2007): 275-278.

[26] M. Kato, H. Ota, M. Okuda, et al., “Guidelines for the Management of Helicobacter pylori Infection in Japan: 2016 Revised Edition,” Helicobacter 24, no. 4 (2019): e12597, https://doi.org/10.1111/hel.12597.

[27] C. A. Fallone, N. Chiba, S. V. van Zanten, et al., “The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults,” Gastroenterology 151, no. 1 (2016): 51-69.e14.

[28] H.-K. Jung, S. J. Kang, Y. C. Lee, et al., “Evidence-Based Guidelines for the Treatment of Helicobacter pylori Infection in Korea 2020,” Gut and Liver 15, no. 2 (2021): 168-195.

[29] M. L. Ouyang, S. P. Zou, Q. Cheng, X. Shi, and M. H. Sun, “Comparative Efficacy and Safety of Potassium-Competitive Acid Blockers and Proton Pump Inhibitors for First-Line Helicobacter pylori Eradication Therapy: A Systematic Review and Network Meta-Analysis,” Helicobacter 29, no. 6 (2024): e13150, https://doi.org/10.1111/hel.13150.

[30] J. J. He, G. Y. Cao, J. C. Yu, et al., “Safety, Tolerability and Pharmacokinetics of Single Ascending and Multiple Oral Doses of Tegoprazan in Healthy Chinese Subjects,” Clinical Drug Investigation 41, no. 1 (2021): 89-97.

[31] D. K. Kim, K.-H. Lee, S.-J. Kim, et al., “Effects of Tegoprazan, a Novel Potassium-Competitive Acid Blocker, on Rat Models of Gastric Acid-Related Disease,” Journal of Pharmacology and Experimental Therapeutics 369, no. 3 (2019): 318-327.

[32] Y. Sakurai, A. Nishimura, G. Kennedy, et al., “Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Rising TAK-438 (Vonoprazan) Doses in Healthy Male Japanese/Non-Japanese Subjects,” Clinical and Translational Gastroenterology 6, no. 6 (2015): e94, https://doi.org/10.1038/ctg.2015.18.

[33] K. Meyer-Rosberg, D. R. Scott, D. Rex, K. Melchers, and G. Sachs, “The Effect of Environmental pH on the Proton Motive Force of Helicobacter pylori,” Gastroenterology 111, no. 4 (1996): 886-900.

[34] S. Han, H. Y. Choi, Y. H. Kim, et al., “Comparison of Pharmacodynamics Between Tegoprazan and Dexlansoprazole Regarding Nocturnal Acid Breakthrough: A Randomized Crossover Study,” Gut and Liver 17, no. 1 (2023): 92-99.

[35] P. J. Kahrilas, N. J. Shaheen, and M. F. Vaezi, “American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease,” Gastroenterology 135, no. 4 (2008): 1392-1413.e5.

[36] L. Laine, S. Spechler, R. Yadlapati, et al., “Vonoprazan Is Efficacious for Treatment of Heartburn in Non-erosive Reflux Disease: A Randomized Trial,” Clinical Gastroenterology and Hepatology 22, no. 11 (2024): 2211-2220.e10.

[37] M. Li, T. Oshima, T. Horikawa, et al., “Systematic Review With Meta-Analysis: Vonoprazan, a Potent Acid Blocker, Is Superior to Proton-Pump Inhibitors for Eradication of Clarithromycin-Resistant Strains of Helicobacter pylori,” Helicobacter 23, no. 4 (2018): e12495, https://doi.org/10.1111/hel.12495.

[38] E. Tshibangu-Kabamba and Y. Yamaoka, “Helicobacter pylori Infection and Antibiotic Resistance — From Biology to Clinical Implications,” Nature Reviews Gastroenterology & Hepatology 18, no. 9 (2021): 613-629.

[39] M. Sanaka, T. Yamamoto, and Y. Kuyama, “Effects of Proton Pump Inhibitors on Gastric Emptying: A Systematic Review,” Digestive Diseases and Sciences 55, no. 9 (2010): 2431-2440.

[40] N. Takahashi and Y. Take, “Tegoprazan, a Novel Potassium-Competitive Acid Blocker to Control Gastric Acid Secretion and Motility,” Journal of Pharmacology and Experimental Therapeutics 364, no. 2 (2018): 275-286.

[41] S. Han, H. Y. Choi, Y. H. Kim, et al., “Randomised Clinical Trial: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Oral Doses of Tegoprazan (CJ-12420), A Novel Potassium-Competitive Acid Blocker, in Healthy Male Subjects,” Alimentary Pharmacology & Therapeutics 50, no. 7 (2019): 751-759.

[42] Y. S. Jung, S. Kim, H.-Y. Kim, S. J. Noh, J. H. Park, and C. H. Park, “7-Day Versus 14-Day Tegoprazan-Based Triple Therapy to Treat Helicobacter pylori Infection: Real-World Evidence,” Journal of Gastroenterology and Hepatology 37, no. 10 (2022): 1911-1918.

[43] N. Kim, “National Health Insurance to Reimburse K-CAB's H. pylori Eradication Indication Prescription,” updated July 3, 2023, https://www.inno-n.com/eng/pr/news/view/2/887.

[44] S. E. Kim, H.-K. Jung, S. J. Kang, et al., “A 10- or 14-Day Bismuth-Containing Quadruple Therapy as a First-Line Helicobacter pylori Eradication Therapy: A Systematic Review and Meta-Analysis,” Korean Journal of Helicobacter and Upper Gastrointestinal Research 21, no. 1 (2021): 48-58.

[45] H. N. Liu, R. Wang, Y. Cao, et al., “Comparison of the Efficacy Between the Dual Therapy of Tegoprazan and the Quadruple Therapy of Tegoprazan: A Randomized Controlled Multicenter Study,” Clinical and Translational Gastroenterology 15, no. 10 (2024): e1, https://doi.org/10.14309/ctg.0000000000000699.

[46] X. Y. Lin, H. P. Huang, Y. J. Liu, et al., “Tegoprazan-Amoxicillin Dual Therapy for Helicobacter pylori Eradication: A Prospective, Randomized, Multicenter Study in Fujian, China,” Helicobacter 29, no. 6 (2024): e13151, https://doi.org/10.1111/hel.13151.

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2025 The Author(s). Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.