Abstract
Background and aims: Glucagon-like peptide-1 receptor agonists (GLP-1ra) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have each shown kidney protective effects in large clinical outcome-studies. The mechanisms behind these effects are sparsely elucidated and the effects of combination therapy remains obscure. In this randomized clinical trial, we compared kidney function in persons with type 2 diabetes receiving either the GLP1-ra semaglutide (SEMA), the SGLT2-i empagliflozin (EMPA) or the combination (COMBI). EMPA treatment was double blinded. Kidney oxygenation was primary outcome and regional (cortex and medulla) assessments were included.
Materials and methods: 80 participants with type 2 diabetes (age 68.1 ± 6.5 years, male 76.25 %, diabetes duration 8[4;12] years), were randomized to either placebo, EMPA, SEMA or COMBI for 32 weeks. Kidney excretory function was assessed by urinary albumine/creatinine ratio (UACR) and glomerular filtration rate (GFR). Magnetic resonance imaging was used to assess kidney oxygenation with R2*(Hz) (higher values indicating lower oxygenation) by a blood oxygen level depedent sequence (BOLD) and renal perfusion (arterial spin labelling (ASL)).
Results: UACR was reduced significantly for the COMBI group (-35% 95% CI [-46;-92]%, p=0.01), with the same tendency for each of the separate treatment arms. GFR decreased significantly from baseline and compared to placebo in all three treatment groups (SEMA -19 mL/min 95% CI [-7;-31]mL/min, p=0.001; EMPA -18 mL/min 95% CI [-6;-30]mL/min, p
Conclusion: Our data demonstrate joined effects of EMPA and SEMA on UACR and GFR and reveal important differential effects of EMPA and SEMA on renal physiology. As hypoxia is considered a main driver in kidney disease, we hypothesized that EMPA and/or SEMA would exert their beneficial effects through improved kidney oxygenation. Contrary to our hypothesis, EMPA treatment for 32 weeks was not associated with improved medullary oxygenation but even slightly reduced it. This is in line with recent rodent studies. SEMA treatment is associated with a substantial reduction in kidney perfusion, probably leading to reduced hyperfiltration. To our knowledge, these effects have not previously been demonstrated in humans.
Materials and methods: 80 participants with type 2 diabetes (age 68.1 ± 6.5 years, male 76.25 %, diabetes duration 8[4;12] years), were randomized to either placebo, EMPA, SEMA or COMBI for 32 weeks. Kidney excretory function was assessed by urinary albumine/creatinine ratio (UACR) and glomerular filtration rate (GFR). Magnetic resonance imaging was used to assess kidney oxygenation with R2*(Hz) (higher values indicating lower oxygenation) by a blood oxygen level depedent sequence (BOLD) and renal perfusion (arterial spin labelling (ASL)).
Results: UACR was reduced significantly for the COMBI group (-35% 95% CI [-46;-92]%, p=0.01), with the same tendency for each of the separate treatment arms. GFR decreased significantly from baseline and compared to placebo in all three treatment groups (SEMA -19 mL/min 95% CI [-7;-31]mL/min, p=0.001; EMPA -18 mL/min 95% CI [-6;-30]mL/min, p
Conclusion: Our data demonstrate joined effects of EMPA and SEMA on UACR and GFR and reveal important differential effects of EMPA and SEMA on renal physiology. As hypoxia is considered a main driver in kidney disease, we hypothesized that EMPA and/or SEMA would exert their beneficial effects through improved kidney oxygenation. Contrary to our hypothesis, EMPA treatment for 32 weeks was not associated with improved medullary oxygenation but even slightly reduced it. This is in line with recent rodent studies. SEMA treatment is associated with a substantial reduction in kidney perfusion, probably leading to reduced hyperfiltration. To our knowledge, these effects have not previously been demonstrated in humans.
| Original language | English |
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| Article number | 85 |
| Journal | Diabetologia |
| Volume | 65 |
| Issue | Suppl 1 |
| ISSN | 0012-186X |
| DOIs | |
| Publication status | Published - Sept 2022 |
| Event | 58 th EASD Annual Meeting of the European Association for the Study of Diabetes - Stockholm, Sweden Duration: 19 Sept 2022 → 23 Sept 2022 |
Conference
| Conference | 58 th EASD Annual Meeting of the European Association for the Study of Diabetes |
|---|---|
| Country/Territory | Sweden |
| City | Stockholm |
| Period | 19/09/2022 → 23/09/2022 |