Genetic variability in sodium-glucose cotransporter 2 and glucagon-like peptide 1 receptor effect on glycemic and pressure control in type 2 diabetes patients treated with SGLT2 inhibitors and GLP-1RA in the everyday clinical practice
AimWe investigated the impact of genetic polymorphisms in the GLP1R and SLC5A2 genes on the response to treatment with glucagon-like peptide-1 receptor (GLP-1R) agonists and sodium-glucose co-transporter-2 (SLGT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) in everyday clinical pract...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1547920/full |
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| author | Gašper Tonin Gašper Tonin Katja Goričar Tanja Blagus Andrej Janež Andrej Janež Vita Dolžan Jasna Klen Jasna Klen |
| author_facet | Gašper Tonin Gašper Tonin Katja Goričar Tanja Blagus Andrej Janež Andrej Janež Vita Dolžan Jasna Klen Jasna Klen |
| author_sort | Gašper Tonin |
| collection | DOAJ |
| description | AimWe investigated the impact of genetic polymorphisms in the GLP1R and SLC5A2 genes on the response to treatment with glucagon-like peptide-1 receptor (GLP-1R) agonists and sodium-glucose co-transporter-2 (SLGT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) in everyday clinical practice.MethodsIn our prospective interventional cohort open-label real-world genetic association study (DRKS-ID: DRKS00034478, https://drks.de/search/en/trial/DRKS00034478), we enrolled 161 clinically well-defined T2DM patients who received SGLT2 inhibitors and/or GLP-1R agonists alongside other medications for 3–6 months. The study’s primary outcomes (HbA1c, body mass, and blood pressure) were measured before the treatment and at the follow-up at 3–6 months. GLP1R rs6923761, rs10305420, and SLC5A2 rs9934336 genotypes were determined by competitive allele-specific polymerase chain reaction. In patients receiving GLP-1R agonists, we analyzed the effect of GLP1R polymorphisms on the patients’ response to treatment, while in patients receiving SGLT2 inhibitors, we analyzed the impact of the SLC5A2 polymorphism on the treatment effect.ResultsTreatment with prescribed antihyperglycemic drugs improved all primary outcomes (p < 0.050). The normal GLP1R rs6923761 G allele was associated with a greater reduction in HbA1c with GLP-1R agonists treatment than the polymorphic A allele in the dominant model (p = 0.029).ConclusionsThe prevalent polymorphic A allele of GLP1R rs6923761 polymorphism was associated with the clinically relevant lower glycemic response to GLP-1R agonists. The described impact extends to everyday clinical practice, indicating that knowledge of these genetic polymorphisms could facilitate the development of targeted and personalized therapy in managing T2DM. |
| format | Article |
| id | doaj-art-c46a0c9ba012443b9ece8c8736dbd38d |
| institution | Matheson Library |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj-art-c46a0c9ba012443b9ece8c8736dbd38d2025-07-07T04:10:24ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-07-011610.3389/fendo.2025.15479201547920Genetic variability in sodium-glucose cotransporter 2 and glucagon-like peptide 1 receptor effect on glycemic and pressure control in type 2 diabetes patients treated with SGLT2 inhibitors and GLP-1RA in the everyday clinical practiceGašper Tonin0Gašper Tonin1Katja Goričar2Tanja Blagus3Andrej Janež4Andrej Janež5Vita Dolžan6Jasna Klen7Jasna Klen8Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaFaculty of Arts, University of Ljubljana, Ljubljana, SloveniaPharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaPharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaDepartment of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaDivision of Internal Medicine, Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, SloveniaPharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaDepartment of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaDivision of Surgery, Department of Abdominal Surgery, University Medical Centre Ljubljana, Ljubljana, SloveniaAimWe investigated the impact of genetic polymorphisms in the GLP1R and SLC5A2 genes on the response to treatment with glucagon-like peptide-1 receptor (GLP-1R) agonists and sodium-glucose co-transporter-2 (SLGT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) in everyday clinical practice.MethodsIn our prospective interventional cohort open-label real-world genetic association study (DRKS-ID: DRKS00034478, https://drks.de/search/en/trial/DRKS00034478), we enrolled 161 clinically well-defined T2DM patients who received SGLT2 inhibitors and/or GLP-1R agonists alongside other medications for 3–6 months. The study’s primary outcomes (HbA1c, body mass, and blood pressure) were measured before the treatment and at the follow-up at 3–6 months. GLP1R rs6923761, rs10305420, and SLC5A2 rs9934336 genotypes were determined by competitive allele-specific polymerase chain reaction. In patients receiving GLP-1R agonists, we analyzed the effect of GLP1R polymorphisms on the patients’ response to treatment, while in patients receiving SGLT2 inhibitors, we analyzed the impact of the SLC5A2 polymorphism on the treatment effect.ResultsTreatment with prescribed antihyperglycemic drugs improved all primary outcomes (p < 0.050). The normal GLP1R rs6923761 G allele was associated with a greater reduction in HbA1c with GLP-1R agonists treatment than the polymorphic A allele in the dominant model (p = 0.029).ConclusionsThe prevalent polymorphic A allele of GLP1R rs6923761 polymorphism was associated with the clinically relevant lower glycemic response to GLP-1R agonists. The described impact extends to everyday clinical practice, indicating that knowledge of these genetic polymorphisms could facilitate the development of targeted and personalized therapy in managing T2DM.https://www.frontiersin.org/articles/10.3389/fendo.2025.1547920/fullpolymorphismSLC5A2GLP1Rtreatment responsetype 2 diabetes mellitusSGLT2 |
| spellingShingle | Gašper Tonin Gašper Tonin Katja Goričar Tanja Blagus Andrej Janež Andrej Janež Vita Dolžan Jasna Klen Jasna Klen Genetic variability in sodium-glucose cotransporter 2 and glucagon-like peptide 1 receptor effect on glycemic and pressure control in type 2 diabetes patients treated with SGLT2 inhibitors and GLP-1RA in the everyday clinical practice Frontiers in Endocrinology polymorphism SLC5A2 GLP1R treatment response type 2 diabetes mellitus SGLT2 |
| title | Genetic variability in sodium-glucose cotransporter 2 and glucagon-like peptide 1 receptor effect on glycemic and pressure control in type 2 diabetes patients treated with SGLT2 inhibitors and GLP-1RA in the everyday clinical practice |
| title_full | Genetic variability in sodium-glucose cotransporter 2 and glucagon-like peptide 1 receptor effect on glycemic and pressure control in type 2 diabetes patients treated with SGLT2 inhibitors and GLP-1RA in the everyday clinical practice |
| title_fullStr | Genetic variability in sodium-glucose cotransporter 2 and glucagon-like peptide 1 receptor effect on glycemic and pressure control in type 2 diabetes patients treated with SGLT2 inhibitors and GLP-1RA in the everyday clinical practice |
| title_full_unstemmed | Genetic variability in sodium-glucose cotransporter 2 and glucagon-like peptide 1 receptor effect on glycemic and pressure control in type 2 diabetes patients treated with SGLT2 inhibitors and GLP-1RA in the everyday clinical practice |
| title_short | Genetic variability in sodium-glucose cotransporter 2 and glucagon-like peptide 1 receptor effect on glycemic and pressure control in type 2 diabetes patients treated with SGLT2 inhibitors and GLP-1RA in the everyday clinical practice |
| title_sort | genetic variability in sodium glucose cotransporter 2 and glucagon like peptide 1 receptor effect on glycemic and pressure control in type 2 diabetes patients treated with sglt2 inhibitors and glp 1ra in the everyday clinical practice |
| topic | polymorphism SLC5A2 GLP1R treatment response type 2 diabetes mellitus SGLT2 |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1547920/full |
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