Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence
Abstract Background In clinical trials enrolling patients with type 2 diabetes (T2D) at high cardiovascular risk, many glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improved albuminuria status and possibly mitigated kidney function loss. However, limited data are available regarding the effe...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-023-01829-0 |
| _version_ | 1827940125607198720 |
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| author | Meir Schechter Cheli Melzer Cohen Alisa Fishkin Aliza Rozenberg Ilan Yanuv Dvora R. Sehtman-Shachar Gabriel Chodick Alice Clark Trine J. Abrahamsen Jack Lawson Avraham Karasik Ofri Mosenzon |
| author_facet | Meir Schechter Cheli Melzer Cohen Alisa Fishkin Aliza Rozenberg Ilan Yanuv Dvora R. Sehtman-Shachar Gabriel Chodick Alice Clark Trine J. Abrahamsen Jack Lawson Avraham Karasik Ofri Mosenzon |
| author_sort | Meir Schechter |
| collection | DOAJ |
| description | Abstract Background In clinical trials enrolling patients with type 2 diabetes (T2D) at high cardiovascular risk, many glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improved albuminuria status and possibly mitigated kidney function loss. However, limited data are available regarding the effects of GLP-1 RAs on albuminuria status and kidney function in real-world settings, including populations with a lower baseline cardiovascular and kidney risk. We assessed the association of GLP-1 RAs initiation with long-term kidney outcomes in the Maccabi Healthcare Services database, Israel. Methods Adults with T2D treated with ≥ 2 glucose-lowering agents who initiated GLP-1 RAs or basal insulin from 2010 to 2019 were propensity-score matched (1:1) and followed until October 2021 (intention-to-treat [ITT]). In an as-treated (AT) analysis, follow-up was also censored at study-drug discontinuation or comparator-initiation. We assessed the risk of a composite kidney outcome, including confirmed ≥ 40% eGFR loss or end-stage kidney disease, and the risk of new macroalbuminuria. Treatment-effect on eGFR slopes was assessed by fitting a linear regression model per patient, followed by a t-test to compare the slopes between the groups. Results Each propensity-score matched group constituted 3424 patients, 45% women, 21% had a history of cardiovascular disease, and 13.9% were treated with sodium-glucose cotransporter-2 inhibitors at baseline. Mean eGFR was 90.6 mL/min/1.73 m2 (SD 19.3) and median UACR was 14.6 mg/g [IQR 0.0–54.7]. Medians follow-up were 81.1 months (ITT) and 22.3 months (AT). The hazard-ratios [95% CI] of the composite kidney outcome with GLP-1 RAs versus basal insulin were 0.96 [0.82–1.11] (p = 0.566) and 0.71 [0.54–0.95] (p = 0.020) in the ITT and AT analyses, respectively. The respective HRs for first new macroalbuminuria were 0.87 [0.75–0.997] and 0.80 [0.64–0.995]. The use of GLP-1 RA was associated with a less steep eGFR slope compared with basal insulin in the AT analysis (mean annual between-group difference of 0.42 mL/min/1.73 m2/year [95%CI 0.11–0.73]; p = 0.008). Conclusion Initiation of GLP-1 RAs in a real-world setting is associated with a reduced risk of albuminuria progression and possible mitigation of kidney function loss in patients with T2D and mostly preserved kidney function. |
| first_indexed | 2024-03-13T09:04:58Z |
| format | Article |
| id | doaj.art-9521c0be51314f39acf728abf59b4868 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-03-13T09:04:58Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-9521c0be51314f39acf728abf59b48682023-05-28T11:07:43ZengBMCCardiovascular Diabetology1475-28402023-05-0122111210.1186/s12933-023-01829-0Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidenceMeir Schechter0Cheli Melzer Cohen1Alisa Fishkin2Aliza Rozenberg3Ilan Yanuv4Dvora R. Sehtman-Shachar5Gabriel Chodick6Alice Clark7Trine J. Abrahamsen8Jack Lawson9Avraham Karasik10Ofri Mosenzon11Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical CenterMaccabi Institute for Research and Innovation, Maccabi Healthcare ServicesDiabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical CenterDiabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical CenterDiabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical CenterDiabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical CenterMaccabi Institute for Research and Innovation, Maccabi Healthcare ServicesNovo Nordisk A/SNovo Nordisk A/SNovo Nordisk A/SMaccabi Institute for Research and Innovation, Maccabi Healthcare ServicesDiabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical CenterAbstract Background In clinical trials enrolling patients with type 2 diabetes (T2D) at high cardiovascular risk, many glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improved albuminuria status and possibly mitigated kidney function loss. However, limited data are available regarding the effects of GLP-1 RAs on albuminuria status and kidney function in real-world settings, including populations with a lower baseline cardiovascular and kidney risk. We assessed the association of GLP-1 RAs initiation with long-term kidney outcomes in the Maccabi Healthcare Services database, Israel. Methods Adults with T2D treated with ≥ 2 glucose-lowering agents who initiated GLP-1 RAs or basal insulin from 2010 to 2019 were propensity-score matched (1:1) and followed until October 2021 (intention-to-treat [ITT]). In an as-treated (AT) analysis, follow-up was also censored at study-drug discontinuation or comparator-initiation. We assessed the risk of a composite kidney outcome, including confirmed ≥ 40% eGFR loss or end-stage kidney disease, and the risk of new macroalbuminuria. Treatment-effect on eGFR slopes was assessed by fitting a linear regression model per patient, followed by a t-test to compare the slopes between the groups. Results Each propensity-score matched group constituted 3424 patients, 45% women, 21% had a history of cardiovascular disease, and 13.9% were treated with sodium-glucose cotransporter-2 inhibitors at baseline. Mean eGFR was 90.6 mL/min/1.73 m2 (SD 19.3) and median UACR was 14.6 mg/g [IQR 0.0–54.7]. Medians follow-up were 81.1 months (ITT) and 22.3 months (AT). The hazard-ratios [95% CI] of the composite kidney outcome with GLP-1 RAs versus basal insulin were 0.96 [0.82–1.11] (p = 0.566) and 0.71 [0.54–0.95] (p = 0.020) in the ITT and AT analyses, respectively. The respective HRs for first new macroalbuminuria were 0.87 [0.75–0.997] and 0.80 [0.64–0.995]. The use of GLP-1 RA was associated with a less steep eGFR slope compared with basal insulin in the AT analysis (mean annual between-group difference of 0.42 mL/min/1.73 m2/year [95%CI 0.11–0.73]; p = 0.008). Conclusion Initiation of GLP-1 RAs in a real-world setting is associated with a reduced risk of albuminuria progression and possible mitigation of kidney function loss in patients with T2D and mostly preserved kidney function.https://doi.org/10.1186/s12933-023-01829-0GLP-1 RABasal insulinChronic kidney diseaseReal world evidenceType 2 diabeteseGFR slope |
| spellingShingle | Meir Schechter Cheli Melzer Cohen Alisa Fishkin Aliza Rozenberg Ilan Yanuv Dvora R. Sehtman-Shachar Gabriel Chodick Alice Clark Trine J. Abrahamsen Jack Lawson Avraham Karasik Ofri Mosenzon Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence Cardiovascular Diabetology GLP-1 RA Basal insulin Chronic kidney disease Real world evidence Type 2 diabetes eGFR slope |
| title | Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence |
| title_full | Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence |
| title_fullStr | Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence |
| title_full_unstemmed | Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence |
| title_short | Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence |
| title_sort | kidney function loss and albuminuria progression with glp 1 receptor agonists versus basal insulin in patients with type 2 diabetes real world evidence |
| topic | GLP-1 RA Basal insulin Chronic kidney disease Real world evidence Type 2 diabetes eGFR slope |
| url | https://doi.org/10.1186/s12933-023-01829-0 |
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