Early biomarkers of diabetic kidney disease. A focus on albuminuria and a new combination of antidiabetic agents

Gómez, Juana Carretero; Ena, Javier; Ripoll, José Miguel Seguí; Carrasco-Sánchez, Francisco Javier; Huelgas, Ricardo Gómez; Polo, Lourdes Mateos; Aguilar, José Manuel Varela; Tembra, José M Suárez; Arévalo-Lorido, José Carlos; Diabetes, Obesity

doi:10.1111/ijcp.13586

Cited by 4 publications

(5 citation statements)

References 26 publications

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“…UACR did not decrease significantly in any of the groups, probably because of the small number of participants per group. Two previous studies have found similar reductions in UACR compared with baseline for the combination treatment [39,40]. Furthermore, the small reduction in UACR in the empagliflozin group might be attributed to the low baseline values (Table 1) and, as changes in oxygenation may precede changes in UACR, we were not able to fully establish the link between the two.…”

Section: Discussionmentioning

confidence: 59%

Separate and combined effects of semaglutide and empagliflozin on kidney oxygenation and perfusion in people with type 2 diabetes: a randomised trial

et al. 2023

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Aims/hypothesis Glucagon-like peptide-1 receptor agonists (GLP-1ras) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown kidney-protective effects. Improved kidney oxygenation and haemodynamic changes are suggested mechanisms; however, human data are scarce. We therefore investigated whether semaglutide (GLP-1ra), empagliflozin (SGLT2i) or their combination improve kidney oxygenation and perfusion. Methods The trial was undertaken at Aarhus University Hospital, Denmark. A total of 120 people with type 2 diabetes (HbA 1c ≥48 mmol/mol [6.5%]) and at high risk of CVD (age ≥50 years) were randomised into four parallel groups (n=30 in each group) for 32 weeks: 1.0 mg semaglutide (open label); 10 mg empagliflozin (blinded to participants, caregivers, examiners and outcome assessors); their combination (1.0 mg semaglutide open label plus 10 mg empagliflozin blinded to participants, caregivers, examiners and outcome assessors); and placebo tablet (blinded to participants, caregivers, examiners and outcome assessors). Sequentially numbered, sealed envelopes containing computer-generated randomisation codes, provided by Glostrup Pharmacy, Glostrup, Denmark, determined the intervention. The two co-primary outcomes were change in kidney oxygenation and change in arterial stiffness. This paper reports on kidney oxygenation, for which 80 individuals as prespecified, 20 in each group, underwent MRI. We primarily hypothesised that kidney oxygenation would be improved in the active treatment groups compared with placebo after 32 weeks. Secondary outcomes included changes in kidney perfusion, erythropoietin, haematocrit, urine albumin/creatinine ratio (UACR) and GFR (measured using technetium-99m) compared with baseline and between treatment groups at week 32. Results Our model estimated a common baseline R2* value across all four groups in the cortex and the medulla. At baseline, the value was 24.5 (95% CI 23.9, 24.9) Hz in the medulla. After 32 weeks, the R2* values in the medulla were estimated to be 25.4 (95% CI 24.7, 26.2) Hz in the empagliflozin group and 24.5 (95% CI 23.9, 25.1) Hz in the placebo group (p=0.016) (higher R2* corresponds to a lower oxygenation). Semaglutide decreased perfusion in both the cortex and the medulla. Empagliflozin increased erythropoietin and haematocrit. All three active treatments decreased GFR but not UACR. Ten serious adverse events were reported, among them two occurrences of semaglutide-associated obstipation.

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Section: Discussionmentioning

confidence: 59%

Separate and combined effects of semaglutide and empagliflozin on kidney oxygenation and perfusion in people with type 2 diabetes: a randomised trial

et al. 2023

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“…In the study by Carretero-Gomez et al [ 28 ], the extent of reduction in the total UACR was significant and similar when the combination was started simultaneously or when a GLP-1RA was added to ongoing SGLT2i therapy (− 17.19 mg/g and − 16.4 mg/g, respectively; p < 0.0001). A greater reduction in macroalbuminuria was observed when an SGLT2i was added to a GLP-1RA than when a GLP-1RA was added to an SGLT2i (− 116.7 mg/g [n = 24] and − 55.5 mg/g [n = 21]; p < 0.005).…”

Section: Resultsmentioning

confidence: 87%

“…3 E). Two studies (Carretero-Gomez et al [ 28 ] and Diaz-Trastoy et al [ 26 ]) reported results related to albuminuria. In the study by Carretero-Gomez et al [ 28 ], there was a significant reduction in total urinary albumin-to–creatinine ratio (UACR; − 15.14 mg/g; p < 0.0001) and macroalbuminuria (UACR > 30 mg/g; − 63.18 mg/g; p < 0.0001) at 26 weeks.…”

Section: Resultsmentioning

confidence: 99%

“…Two studies (Carretero-Gomez et al [ 28 ] and Diaz-Trastoy et al [ 26 ]) reported results related to albuminuria. In the study by Carretero-Gomez et al [ 28 ], there was a significant reduction in total urinary albumin-to–creatinine ratio (UACR; − 15.14 mg/g; p < 0.0001) and macroalbuminuria (UACR > 30 mg/g; − 63.18 mg/g; p < 0.0001) at 26 weeks. In the study by Diaz-Trastoy et al [ 26 ], albuminuria data were available for 127 of 212 patients, 10 patients progressed from normoalbuminuria to micro- and macroalbuminuria, and 13 patients showed regression.…”

Section: Resultsmentioning

confidence: 99%

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Effectiveness and safety of the combination of sodium–glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies

Ahmad,

Sabbour

2024

Cardiovasc Diabetol

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Background Randomized controlled trials and real-world studies suggest that combination therapy with sodium–glucose transport protein 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated with improvement in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), body mass index (BMI), and total cholesterol levels. However, a systematic review of available real-world evidence may facilitate clinical decision-making in the real-world scenario. This meta-analysis assessed the safety and effectiveness of combinations of SGLT2is + GLP-1RAs with a focus on their cardioprotective effects along with glucose-lowering ability in patients with type 2 diabetes mellitus (T2DM) in a real-world setting. Methods Electronic searches were performed in the PubMed/MEDLINE, PROQuest, Scopus, CINAHL, and Google Scholar databases. Qualitative analyses and meta-analyses were performed using the Joanna Briggs Institute SUMARI software package and Review Manager v5.4, respectively. Results The initial database search yielded 1445 articles; of these, 13 were included in this study. The analyses indicated that SGLT2is + GLP-1RAs combinations were associated with significantly lower all-cause mortality when compared with individual therapies (odds ratio [95% confidence interval [CI] 0.49 [0.41, 0.60]; p < 0.00001). Significant reductions in BMI (− 1.71 [− 2.74, − 0.67]; p = 0.001), SBP (− 6.35 [− 10.17, − 2.53]; p = 0.001), HbA1c levels (− 1.48 [− 1.75, − 1.21]; p < 0.00001), and FPG (− 2.27 [− 2.78, − 1.76]; p < 0.00001) were associated with the simultaneous administration of the combination. Changes in total cholesterol levels and differences between simultaneous and sequential combination therapies for this outcome were not significant. Conclusion This systematic review and meta-analysis based on real-world data suggests that the combination of SGLT2is + GLP-1RAs is associated with lower all-cause mortality and favorable improvements in cardiovascular, renal, and glycemic measurements. The findings drive a call-to–action to incorporate this combination early and simultaneously in managing T2DM patients and achieve potential cardiovascular benefits and renal protection. Graphical Abstract

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“…A post hoc analysis in the CREDENCE trial showed a greater relative reduction in UACR in patients with lower baseline albuminuria levels [29] . Combined treatment of GLP-1RA and SGLT2i has beneficial effects on UACR [30] . In patients with type 1 diabetes and a baseline UACR ≥ 30 mg/g, solagliflozin was able to reduce UACR [31] .…”

Section: Discussionmentioning

confidence: 99%

Relationship between dapagliflozin and urinary albumin-to-creatinine ratio in patients with diabetes mellitus and cardiovascular disease: an observational study

Wu,

He,

Xia

et al. 2023

Cardiology Plus

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Background and purpose: The potential impact of dapagliflozin on the urinary albumin-to-creatinine ratio (UACR) in patients with type 2 diabetes and cardiovascular disease remained inconclusive. We aimed to investigate the potential impact of dapagliflozin on the UACR in patients with diabetes mellitus complicated with cardiovascular disease. Methods: This is a single-center prospective observation study. Diabetic patients with cardiovascular disease were recruited at authors’ center (both outpatients and inpatients) during a period from June 2019 to November 2020. The study subjects were grouped into a dapagliflozin group (receiving dapagliflozin for at least 6 consecutive months) and a non-sodium-glucose cotransporter 2 inhibitors (SGLT2i) group (not receiving dapagliflozin or any other SGLT2i). LgUACR change at 6 months from the baseline were compared between the two groups. Results: A total of 57 patients were enrolled during a period from June 2019 to November 2020: 35 in the dapagliflozin group versus 22 in the non-SGLT2i group. LgUACR change from the baseline was −0.07 in the dapagliflozin group, and 0.17 in the non-SGLT2i group (P = 0.021). Dapagliflozin was associated with a decrease in UACR in the univariate regression analysis but not in the analysis of covariance. Conclusions: Dapagliflozin may be associated with a decrease in the UACR in patients with diabetes mellitus and cardiovascular disease. In view of the limited sample size, further investigation is needed to verify these findings.

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Early biomarkers of diabetic kidney disease. A focus on albuminuria and a new combination of antidiabetic agents

Cited by 4 publications

References 26 publications

Separate and combined effects of semaglutide and empagliflozin on kidney oxygenation and perfusion in people with type 2 diabetes: a randomised trial

Separate and combined effects of semaglutide and empagliflozin on kidney oxygenation and perfusion in people with type 2 diabetes: a randomised trial

Effectiveness and safety of the combination of sodium–glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies

Relationship between dapagliflozin and urinary albumin-to-creatinine ratio in patients with diabetes mellitus and cardiovascular disease: an observational study

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