Samoilova IuG, Vaizova OE, Stankova AE, Matveeva MV, Podchinenova DV, Kudlay DA, Borozinets AA, Filippova TA, Grishkevich IR, Partala AV, Gerasimova DA. Pharmacogenetics of dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes mellitus: A review. Terapevticheskii Arkhiv (Ter. Arkh.). 2024;96(1):63–67.
DOI: 10.26442/00403660.2024.01.202553
Фармакогенетика ингибиторов дипептидилпептидазы-4 в лечении сахарного диабета 2-го типа
Samoilova IuG, Vaizova OE, Stankova AE, Matveeva MV, Podchinenova DV, Kudlay DA, Borozinets AA, Filippova TA, Grishkevich IR, Partala AV, Gerasimova DA. Pharmacogenetics of dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes mellitus: A review. Terapevticheskii Arkhiv (Ter. Arkh.). 2024;96(1):63–67.
DOI: 10.26442/00403660.2024.01.202553
В обзоре рассмотрены публикации, в которых исследованы генетические полиморфизмы генов, потенциально оказывающих влияние на эффективность терапии сахароснижающими препаратами группы ингибиторов дипептидилпептидазы-4. Поиск публикаций осуществляли в базе данных PubMed с 2017 по 2023 г. Полиморфизмы нескольких генов (GLP1R, TCF7L2, DPP-4, KCNQ1, KCNJ11, PNPLA3, PRKD1) связаны с фармакокинетикой и эффективностью ингибиторов дипептидилпептидазы-4, что может быть перспективным в отношении персонализации лечения пациентов с сахарным диабетом 2-го типа.
Ключевые слова: полиморфизм, ингибиторы дипептидилпептидазы-4, сахарный диабет 2-го типа, GLP1R, TCF7L2, DPP-4, KCNQ1
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The review addresses publications on genetic polymorphisms that potentially impact the effectiveness of therapy with hypoglycemic drugs of the dipeptidyl peptidase-4 inhibitor group. The literature was searched in the PubMed database from 2017 to 2023. Polymorphisms of several genes (GLP1R, TCF7L2, DPP-4, KCNQ1, KCNJ11, PNPLA3, PRKD1) are associated with the pharmacokinetic values and efficacy of dipeptidyl peptidase-4 inhibitors, which may be promising for personalizing the treatment of patients with type 2 diabetes mellitus.
1. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88-98. DOI:10.1038/nrendo.2017.151
2. Tinajero MG, Malik VS. An Update on the Epidemiology of Type 2 Diabetes: A Global Perspective. Endocrinol Metab Clin North Am. 2021;50(3):337-55. DOI:10.1016/j.ecl.2021.05.013
3. Sun H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119. DOI:10.1016/j.diabres.2021.109119
4. Holst JJ, Rosenkilde MM. GIP as a Therapeutic Target in Diabetes and Obesity: Insight From Incretin Co-agonists. J Clin Endocrinol Metab. 2020;105(8):e2710-6. DOI:10.1210/clinem/dgaa327
5. Deacon CF. Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2020;16(11):642-53. DOI:10.1038/s41574-020-0399-8
6. Sesti G, Avogaro A, Belcastro S, et al. Ten years of experience with DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. Acta Diabetol. 2019;56(6):605-17. DOI:10.1007/s00592-018-1271-3
7. Maloney A, Rosenstock J, Fonseca V. A Model-Based Meta-Analysis of 24 Antihyperglycemic Drugs for Type 2 Diabetes: Comparison of Treatment Effects at Therapeutic Doses. Clin Pharmacol Ther. 2019;105(5):1213-23. DOI:10.1002/cpt.1307
8. Cho YK, Kang YM, Lee SE, et al. Efficacy and safety of combination therapy with SGLT2 and DPP4 inhibitors in the treatment of type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab. 2018;44(5):393-401. DOI:10.1016/j.diabet.2018.01.011
9. Feingold KR. Oral and Injectable (Non-Insulin) Pharmacological Agents for the Treatment of Type 2 Diabetes. 2022 Aug 26. In: Feingold KR, Anawalt B, Blackman MR, et al, ed. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. PMID: 25905364
10. Li D, Shi W, Wang T, Tang H. SGLT2 inhibitor plus DPP-4 inhibitor as combination therapy for type 2 diabetes: A systematic review and meta-analysis. Diabetes Obes Metab. 2018;20(8):1972-6. DOI:10.1111/dom.13294
11. Tasanen K, Varpuluoma O, Nishie W. Dipeptidyl Peptidase-4 Inhibitor-Associated Bullous Pemphigoid. Front Immunol. 2019;10:1238. DOI:10.3389/fimmu.2019.01238
12. Pinto LC, Rados DV, Barkan SS, et al. Dipeptidyl peptidase-4 inhibitors, pancreatic cancer and acute pancreatitis: A meta-analysis with trial sequential analysis. Sci Rep. 2018;8(1):782. DOI:10.1038/s41598-017-19055-6
13. Kanie T, Mizuno A, Takaoka Y, et al. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis. Cochrane Database Syst Rev. 2021;10(10):CD013650. DOI:10.1002/14651858.CD013650.pub2
14. Men P, He N, Song C, Zhai S. Dipeptidyl peptidase-4 inhibitors and risk of arthralgia: A systematic review and meta-analysis. Diabetes Metab. 2017;43(6):493-500. DOI:10.1016/j.diabet.2017.05.013
15. Rosenstock J, Perkovic V, Johansen OE, et al; CARMELINA Investigators. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial. JAMA. 2019;321(1):69-79. DOI:10.1001/jama.2018.18269
16. Zheng SL, Roddick AJ, Aghar-Jaffar R, et al. Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis. JAMA. 2018;319(15):1580-91. DOI:10.1001/jama.2018.3024
17. Mannino GC, Andreozzi F, Sesti G. Pharmacogenetics of type 2 diabetes mellitus, the route toward tailored medicine. Diabetes Metab Res Rev. 2019;35(3):e3109. DOI:10.1002/dmrr.3109
18. Sayiner ZA, Okyar B, Kısacik B, et al. DPP-4 inhibitors increase the incidence of arthritis/arthralgia but do not affect autoimmunity. Acta Endocrinol (Buchar). 2018;14(4):473-6. DOI:10.4183/aeb.2018.473
19. Verheyden MJ, Bilgic A, Murrell DF. A systematic review of drug-induced pemphigoid. Acta Derm Venereol. 2020;100(15):adv00224. DOI:10.2340/00015555-3457
20. Jedlowski PM, Jedlowski MF, Fazel MT. DPP-4 Inhibitors and Increased Reporting Odds of Bullous Pemphigoid: A Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS) from 2006 to 2020. Am J Clin Dermatol. 2021;22(6):891-900. DOI:10.1007/s40257-021-00625-4
21. Arai M, Shirakawa J, Konishi H, et al. Bullous pemphigoid and dipeptidyl peptidase 4 inhibitors: A disproportionality analysis based on the Japanese Adverse Drug Event Report Database. Diabetes Care. 2018;41(9):e130-2. DOI:10.2337/dc18-0210
22. Carnovale C, Mazhar F, Arzenton E, et al. Bullous pemphigoid induced by dipeptidyl peptidase-4 (DPP-4) inhibitors: a pharmacovigilance-pharmacodynamic/pharmacokinetic assessment through an analysis of the vigibase®. Expert Opin Drug Saf. 2019;18(11):1099-108. DOI:10.1080/14740338.2019.1668373
23. Rychlik-Sych M, Barańska M, Dudarewicz M, et al. Haplotypes of ABCB1 1236C >T (rs1128503), 2677G >T/A (rs2032582), and 3435C >T (rs1045642) in patients with bullous pemphigoid. Arch Dermatol Res. 2018;310(6):515-22. DOI:10.1007/s00403-018-1842-8
24. Nasykhova YA, Tonyan ZN, Mikhailova AA, et al. Pharmacogenetics of Type 2 Diabetes-Progress and Prospects. Int J Mol Sci. 2020;21(18):6842. DOI:10.3390/ijms21186842
25. Javorský M, Gotthardová I, Klimčáková L, et al. A missense variant in GLP1R gene is associated with the glycaemic response to treatment with gliptins. Diabetes Obes Metab. 2016;18:941-4. DOI:10.1111/dom.12682
26. Mashayekhi M, Wilson J, Jafarian-Kerman SR, Brown N. OR05-6 The Effect of the GLP1R Variant rs6923761 on Post-Prandial Glucose Levels during Treatment with Sitagliptin. J Endocr Soc. 2019;3(Suppl. 1). DOI:10.1210/js.2019-OR05-6
27. Űrgeová A, Javorský M, Klimčáková L, et al. Genetic variants associated with glycemic response to treatment with dipeptidylpeptidase 4 inhibitors. Pharmacogenomics. 2020;21(5):317-23. DOI:10.2217/pgs-2019-0147
28. Ferreira MC, da Silva MER, Fukui RT, et al. Effect of TCF7L2 polymorphism on pancreatic hormones after exenatide in type 2 diabetes. Diabetol Metab Syndr. 2019;11:10. DOI:10.1186/s13098-019-0401-6
29. Gotthardová I, Javorský M, Klimčáková L, et al. KCNQ1 gene polymorphism is associated with glycaemic response to treatment with DPP-4 inhibitors. Diabetes Res Clin Pract. 2017;130:142-7. DOI:10.1016/j.diabres.2017.05.018
30. Barata L, Feitosa MF, Bielak LF, et al. Insulin Resistance Exacerbates Genetic Predisposition to Nonalcoholic Fatty Liver Disease in Individuals Without Diabetes. Hepatol Commun. 2019;3(7):894-907. DOI:10.1002/hep4.1353
31. Liao WL, Lee WJ, Chen CC, et al. Pharmacogenetics of dipeptidyl peptidase 4 inhibitors in a Taiwanese population with type 2 diabetes. Oncotarget. 2017;8(11):18050-8. DOI:10.18632/oncotarget.14951
________________________________________________
1. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88-98. DOI:10.1038/nrendo.2017.151
2. Tinajero MG, Malik VS. An Update on the Epidemiology of Type 2 Diabetes: A Global Perspective. Endocrinol Metab Clin North Am. 2021;50(3):337-55. DOI:10.1016/j.ecl.2021.05.013
3. Sun H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119. DOI:10.1016/j.diabres.2021.109119
4. Holst JJ, Rosenkilde MM. GIP as a Therapeutic Target in Diabetes and Obesity: Insight From Incretin Co-agonists. J Clin Endocrinol Metab. 2020;105(8):e2710-6. DOI:10.1210/clinem/dgaa327
5. Deacon CF. Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2020;16(11):642-53. DOI:10.1038/s41574-020-0399-8
6. Sesti G, Avogaro A, Belcastro S, et al. Ten years of experience with DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. Acta Diabetol. 2019;56(6):605-17. DOI:10.1007/s00592-018-1271-3
7. Maloney A, Rosenstock J, Fonseca V. A Model-Based Meta-Analysis of 24 Antihyperglycemic Drugs for Type 2 Diabetes: Comparison of Treatment Effects at Therapeutic Doses. Clin Pharmacol Ther. 2019;105(5):1213-23. DOI:10.1002/cpt.1307
8. Cho YK, Kang YM, Lee SE, et al. Efficacy and safety of combination therapy with SGLT2 and DPP4 inhibitors in the treatment of type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab. 2018;44(5):393-401. DOI:10.1016/j.diabet.2018.01.011
9. Feingold KR. Oral and Injectable (Non-Insulin) Pharmacological Agents for the Treatment of Type 2 Diabetes. 2022 Aug 26. In: Feingold KR, Anawalt B, Blackman MR, et al, ed. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. PMID: 25905364
10. Li D, Shi W, Wang T, Tang H. SGLT2 inhibitor plus DPP-4 inhibitor as combination therapy for type 2 diabetes: A systematic review and meta-analysis. Diabetes Obes Metab. 2018;20(8):1972-6. DOI:10.1111/dom.13294
11. Tasanen K, Varpuluoma O, Nishie W. Dipeptidyl Peptidase-4 Inhibitor-Associated Bullous Pemphigoid. Front Immunol. 2019;10:1238. DOI:10.3389/fimmu.2019.01238
12. Pinto LC, Rados DV, Barkan SS, et al. Dipeptidyl peptidase-4 inhibitors, pancreatic cancer and acute pancreatitis: A meta-analysis with trial sequential analysis. Sci Rep. 2018;8(1):782. DOI:10.1038/s41598-017-19055-6
13. Kanie T, Mizuno A, Takaoka Y, et al. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis. Cochrane Database Syst Rev. 2021;10(10):CD013650. DOI:10.1002/14651858.CD013650.pub2
14. Men P, He N, Song C, Zhai S. Dipeptidyl peptidase-4 inhibitors and risk of arthralgia: A systematic review and meta-analysis. Diabetes Metab. 2017;43(6):493-500. DOI:10.1016/j.diabet.2017.05.013
15. Rosenstock J, Perkovic V, Johansen OE, et al; CARMELINA Investigators. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial. JAMA. 2019;321(1):69-79. DOI:10.1001/jama.2018.18269
16. Zheng SL, Roddick AJ, Aghar-Jaffar R, et al. Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis. JAMA. 2018;319(15):1580-91. DOI:10.1001/jama.2018.3024
17. Mannino GC, Andreozzi F, Sesti G. Pharmacogenetics of type 2 diabetes mellitus, the route toward tailored medicine. Diabetes Metab Res Rev. 2019;35(3):e3109. DOI:10.1002/dmrr.3109
18. Sayiner ZA, Okyar B, Kısacik B, et al. DPP-4 inhibitors increase the incidence of arthritis/arthralgia but do not affect autoimmunity. Acta Endocrinol (Buchar). 2018;14(4):473-6. DOI:10.4183/aeb.2018.473
19. Verheyden MJ, Bilgic A, Murrell DF. A systematic review of drug-induced pemphigoid. Acta Derm Venereol. 2020;100(15):adv00224. DOI:10.2340/00015555-3457
20. Jedlowski PM, Jedlowski MF, Fazel MT. DPP-4 Inhibitors and Increased Reporting Odds of Bullous Pemphigoid: A Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS) from 2006 to 2020. Am J Clin Dermatol. 2021;22(6):891-900. DOI:10.1007/s40257-021-00625-4
21. Arai M, Shirakawa J, Konishi H, et al. Bullous pemphigoid and dipeptidyl peptidase 4 inhibitors: A disproportionality analysis based on the Japanese Adverse Drug Event Report Database. Diabetes Care. 2018;41(9):e130-2. DOI:10.2337/dc18-0210
22. Carnovale C, Mazhar F, Arzenton E, et al. Bullous pemphigoid induced by dipeptidyl peptidase-4 (DPP-4) inhibitors: a pharmacovigilance-pharmacodynamic/pharmacokinetic assessment through an analysis of the vigibase®. Expert Opin Drug Saf. 2019;18(11):1099-108. DOI:10.1080/14740338.2019.1668373
23. Rychlik-Sych M, Barańska M, Dudarewicz M, et al. Haplotypes of ABCB1 1236C >T (rs1128503), 2677G >T/A (rs2032582), and 3435C >T (rs1045642) in patients with bullous pemphigoid. Arch Dermatol Res. 2018;310(6):515-22. DOI:10.1007/s00403-018-1842-8
24. Nasykhova YA, Tonyan ZN, Mikhailova AA, et al. Pharmacogenetics of Type 2 Diabetes-Progress and Prospects. Int J Mol Sci. 2020;21(18):6842. DOI:10.3390/ijms21186842
25. Javorský M, Gotthardová I, Klimčáková L, et al. A missense variant in GLP1R gene is associated with the glycaemic response to treatment with gliptins. Diabetes Obes Metab. 2016;18:941-4. DOI:10.1111/dom.12682
26. Mashayekhi M, Wilson J, Jafarian-Kerman SR, Brown N. OR05-6 The Effect of the GLP1R Variant rs6923761 on Post-Prandial Glucose Levels during Treatment with Sitagliptin. J Endocr Soc. 2019;3(Suppl. 1). DOI:10.1210/js.2019-OR05-6
27. Űrgeová A, Javorský M, Klimčáková L, et al. Genetic variants associated with glycemic response to treatment with dipeptidylpeptidase 4 inhibitors. Pharmacogenomics. 2020;21(5):317-23. DOI:10.2217/pgs-2019-0147
28. Ferreira MC, da Silva MER, Fukui RT, et al. Effect of TCF7L2 polymorphism on pancreatic hormones after exenatide in type 2 diabetes. Diabetol Metab Syndr. 2019;11:10. DOI:10.1186/s13098-019-0401-6
29. Gotthardová I, Javorský M, Klimčáková L, et al. KCNQ1 gene polymorphism is associated with glycaemic response to treatment with DPP-4 inhibitors. Diabetes Res Clin Pract. 2017;130:142-7. DOI:10.1016/j.diabres.2017.05.018
30. Barata L, Feitosa MF, Bielak LF, et al. Insulin Resistance Exacerbates Genetic Predisposition to Nonalcoholic Fatty Liver Disease in Individuals Without Diabetes. Hepatol Commun. 2019;3(7):894-907. DOI:10.1002/hep4.1353
31. Liao WL, Lee WJ, Chen CC, et al. Pharmacogenetics of dipeptidyl peptidase 4 inhibitors in a Taiwanese population with type 2 diabetes. Oncotarget. 2017;8(11):18050-8. DOI:10.18632/oncotarget.14951
1ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава России, Томск, Россия; 2ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия; 3ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова», Москва, Россия; 4ФГБУ «Государственный научный центр “Институт иммунологии”» ФМБА России
*samoilova_y@inbox.ru
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Iuliia G. Samoilova*1, Olga E. Vaizova1, Anastasia E. Stankova1, Mariia V. Matveeva1, Daria V. Podchinenova1, Dmitry A. Kudlay2–4, Anastasiia A. Borozinets2, Tatyana A. Filippova1, Ivan R. Grishkevich1, Anastasia V. Partala1, Diana A. Gerasimova1
1Siberia State Medical University, Tomsk, Russia; 2Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; 3Lomonosov Moscow State University, Moscow, Russia; 4National Research Center – Institute of Immunology, Moscow, Russia
*samoilova_y@inbox.ru