Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis
Abstract Background Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects. This post hoc analysis investigated the association between major adverse cardiovascular events (MACE) and baselin...
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-023-01949-7 |
| _version_ | 1797578345703014400 |
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| author | Peter Rossing Stephen C. Bain Heidrun Bosch-Traberg Ekaterina Sokareva Hiddo J. L. Heerspink Søren Rasmussen Linda G. Mellbin |
| author_facet | Peter Rossing Stephen C. Bain Heidrun Bosch-Traberg Ekaterina Sokareva Hiddo J. L. Heerspink Søren Rasmussen Linda G. Mellbin |
| author_sort | Peter Rossing |
| collection | DOAJ |
| description | Abstract Background Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects. This post hoc analysis investigated the association between major adverse cardiovascular events (MACE) and baseline kidney parameters and whether the effect of semaglutide on MACE risk was impacted by baseline kidney parameters in people with T2D at high cardiovascular risk. Methods Participants from the SUSTAIN 6 and PIONEER 6 trials, receiving semaglutide or placebo, were categorised according to baseline kidney function (estimated glomerular filtration rate [eGFR] < 45 and ≥ 45–<60 versus ≥ 60 mL/min/1.73 m2) or damage (urine albumin:creatinine ratio [UACR] ≥ 30–≤300 and > 300 versus < 30 mg/g). Relative risk of first MACE by baseline kidney parameters was evaluated using a Cox proportional hazards model. The same model, adjusted with inverse probability weighting, and a quadratic spline regression were applied to evaluate the effect of semaglutide on risk and event rate of first MACE across subgroups. The semaglutide effects on glycated haemoglobin (HbA1c), body weight (BW) and serious adverse events (SAEs) across subgroups were also evaluated. Results Independently of treatment, participants with reduced kidney function (eGFR ≥ 45–<60 and < 45 mL/min/1.73 m2: hazard ratio [95% confidence interval]; 1.36 [1.04;1.76] and 1.52 [1.15;1.99]) and increased albuminuria (UACR ≥ 30–≤300 and > 300 mg/g: 1.53 [1.14;2.04] and 2.52 [1.84;3.42]) had an increased MACE risk versus those without. Semaglutide consistently reduced MACE risk versus placebo across all eGFR and UACR subgroups (interaction p value [pINT] > 0.05). Semaglutide reduced HbA1c regardless of baseline eGFR and UACR (pINT>0.05); reductions in BW were affected by baseline eGFR (pINT<0.001) but not UACR (pINT>0.05). More participants in the lower eGFR or higher UACR subgroups experienced SAEs versus participants in reference groups; the number of SAEs was similar between semaglutide and placebo arms in each subgroup. Conclusions MACE risk was greater for participants with kidney impairment or damage than for those without. Semaglutide consistently reduced MACE risk across eGFR and UACR subgroups, indicating that semaglutide provides cardiovascular benefits in people with T2D and at high cardiovascular risk across a broad spectrum of kidney function and damage. Trial registrations NCT01720446; NCT02692716. |
| first_indexed | 2024-03-10T22:20:38Z |
| format | Article |
| id | doaj.art-c520c57dfa9343559d55cf333ed71c54 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-03-10T22:20:38Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-c520c57dfa9343559d55cf333ed71c542023-11-19T12:17:21ZengBMCCardiovascular Diabetology1475-28402023-08-0122111110.1186/s12933-023-01949-7Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysisPeter Rossing0Stephen C. Bain1Heidrun Bosch-Traberg2Ekaterina Sokareva3Hiddo J. L. Heerspink4Søren Rasmussen5Linda G. Mellbin6Steno Diabetes CenterSwansea University Medical SchoolNovo Nordisk A/SNovo Nordisk A/SUniversity of GroningenNovo Nordisk A/SKarolinska InstitutetAbstract Background Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects. This post hoc analysis investigated the association between major adverse cardiovascular events (MACE) and baseline kidney parameters and whether the effect of semaglutide on MACE risk was impacted by baseline kidney parameters in people with T2D at high cardiovascular risk. Methods Participants from the SUSTAIN 6 and PIONEER 6 trials, receiving semaglutide or placebo, were categorised according to baseline kidney function (estimated glomerular filtration rate [eGFR] < 45 and ≥ 45–<60 versus ≥ 60 mL/min/1.73 m2) or damage (urine albumin:creatinine ratio [UACR] ≥ 30–≤300 and > 300 versus < 30 mg/g). Relative risk of first MACE by baseline kidney parameters was evaluated using a Cox proportional hazards model. The same model, adjusted with inverse probability weighting, and a quadratic spline regression were applied to evaluate the effect of semaglutide on risk and event rate of first MACE across subgroups. The semaglutide effects on glycated haemoglobin (HbA1c), body weight (BW) and serious adverse events (SAEs) across subgroups were also evaluated. Results Independently of treatment, participants with reduced kidney function (eGFR ≥ 45–<60 and < 45 mL/min/1.73 m2: hazard ratio [95% confidence interval]; 1.36 [1.04;1.76] and 1.52 [1.15;1.99]) and increased albuminuria (UACR ≥ 30–≤300 and > 300 mg/g: 1.53 [1.14;2.04] and 2.52 [1.84;3.42]) had an increased MACE risk versus those without. Semaglutide consistently reduced MACE risk versus placebo across all eGFR and UACR subgroups (interaction p value [pINT] > 0.05). Semaglutide reduced HbA1c regardless of baseline eGFR and UACR (pINT>0.05); reductions in BW were affected by baseline eGFR (pINT<0.001) but not UACR (pINT>0.05). More participants in the lower eGFR or higher UACR subgroups experienced SAEs versus participants in reference groups; the number of SAEs was similar between semaglutide and placebo arms in each subgroup. Conclusions MACE risk was greater for participants with kidney impairment or damage than for those without. Semaglutide consistently reduced MACE risk across eGFR and UACR subgroups, indicating that semaglutide provides cardiovascular benefits in people with T2D and at high cardiovascular risk across a broad spectrum of kidney function and damage. Trial registrations NCT01720446; NCT02692716.https://doi.org/10.1186/s12933-023-01949-7Type 2 diabetesCardiovascular diseaseKidney diseaseGlucagon-like peptide-1 receptor agonistSemaglutideMajor cardiovascular events |
| spellingShingle | Peter Rossing Stephen C. Bain Heidrun Bosch-Traberg Ekaterina Sokareva Hiddo J. L. Heerspink Søren Rasmussen Linda G. Mellbin Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis Cardiovascular Diabetology Type 2 diabetes Cardiovascular disease Kidney disease Glucagon-like peptide-1 receptor agonist Semaglutide Major cardiovascular events |
| title | Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis |
| title_full | Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis |
| title_fullStr | Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis |
| title_full_unstemmed | Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis |
| title_short | Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis |
| title_sort | effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease sustain 6 and pioneer 6 post hoc pooled analysis |
| topic | Type 2 diabetes Cardiovascular disease Kidney disease Glucagon-like peptide-1 receptor agonist Semaglutide Major cardiovascular events |
| url | https://doi.org/10.1186/s12933-023-01949-7 |
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