Albuminuria‐lowering effect of adding semaglutide on top of empagliflozin in individuals with type 2 diabetes: A randomized and placebo‐controlled study

Sivalingam, Suvanjaa; Wasehuus, Victor Soendergaard; Rotbain Curovic, Viktor; Blond, Martin Bæk; Hansen, Tine W.; Persson, Frederik; Rossing, Peter

doi:10.1111/dom.15287

Cited by 10 publications

(3 citation statements)

References 47 publications

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“…Three other studies have investigated the effect of combination treatment on UACR. [45][46][47] All observed a similar trend with a numerically larger reduction with combination treatment but may have been underpowered to show superiority to monotherapy. As SGLT2is and GLP-1RAs probably confer kidney protection through different mechanisms, combining the two agents could preserve kidney function even further.…”

Section: Discussionmentioning

confidence: 86%

Separate and combined effects of empagliflozin and semaglutide on vascular function: A 32‐week randomized trial

Vernstrøm,

Gullaksen,

Sørensen

et al. 2024

Diabetes Obesity Metabolism

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AimDespite the increasing use of combination treatment with sodium‐glucose cotransporter 2 inhibitors and glucagon‐like peptide‐1 receptor agonists, data are limited on the effects of combination treatment on markers of cardiovascular disease. This study aimed to investigate the effect of empagliflozin, semaglutide, and their combination on vascular function.Materials and MethodsIn total, 120 patients with type 2 diabetes were randomized into four groups (n = 30 in each) for 32 weeks: placebo, semaglutide, empagliflozin, and their combination. The study had two co‐primary outcomes: change in arterial stiffness and kidney oxygenation. This paper reports on arterial stiffness assessed as carotid‐femoral pulse wave velocity. Secondary outcomes included 24‐h blood pressure (BP), 24‐h central BP, urinary albumin to creatinine ratio and glycaemic control assessed by both continuous glucose monitoring and glycated haemoglobin.ResultsThe carotid‐femoral pulse wave velocity did not change significantly in any of the groups compared with placebo. Twenty‐four‐hour systolic BP was reduced by 10 mmHg (95% CI 6–14), p < .001 in the combination group, significantly superior to both placebo and monotherapy (p < .05). Combination treatment increased glycaemic time in range from 72% at baseline to 91% at week 32, p < .001, without increasing time below range. The urinary albumin to creatinine ratio decreased by 36% (95% CI 4–57), p = .03 in the combination group compared with placebo.ConclusionsEmpagliflozin, semaglutide, or their combination did not reduce arterial stiffness. Combination treatment showed a substantial and clinically important reduction in 24‐h systolic BP compared with either treatment alone. Combination treatment increased glycaemic time in range without increasing the risk of hypoglycaemia.

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Section: Discussionmentioning

confidence: 86%

Separate and combined effects of empagliflozin and semaglutide on vascular function: A 32‐week randomized trial

Vernstrøm,

Gullaksen,

Sørensen

et al. 2024

Diabetes Obesity Metabolism

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“…Previous studies have investigated that once-weekly treatment with semaglutide and empagliflozin achieves a significant reduction in HbA1c and can improve glycemic control and plasma aldosterone levels. 73,74 The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) collectively advise using SGLT2 inhibitors or GLP-1R agonists for type 2 diabetes patients with a heightened risk of cardiovascular incidents. 75 Combination treatment of empagliflozin and semaglutide may offer additional cardiovascular protection in patients with type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Effect of Semaglutide and Empagliflozin on Pulmonary Structure and Proteomics in Obese Mice

Yang,

Pan,

Chen

2024

DMSO

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This study utilized proteomics to investigate changes in protein expression associated with lung health in obese mice exposed to semaglutide and empagliflozin through a high-fat diet. Methods: Twenty-eight male C57BL/6JC mice were randomly assigned to two groups: a control diet group (n = 7) and a high-fat diet group (n = 21). The HFD group was further divided into three groups: HFD group (n = 7), Sema group (n = 7), and Empa group (n = 7). Post-treatment, mice underwent assessments including glucose tolerance, lipids, oxidative stress markers, body weight, lung weight, and structure. Proteomics identified differentially expressed proteins (DEPs) in lung tissue, and bioinformatics analyzed the biological processes and functions of these proteins. Results: Semaglutide and empagliflozin significantly attenuated obesity-induced hyperglycemia, abnormal lipid metabolism, oxidative stress response, and can decrease alveolar wall thickness, enlarge alveolar lumen, and reduce collagen content in lung tissue. Both medications also attenuated lung elastic fibre cracking and disintegration. In the HFD/NCD group, there were 66 DEPs, comprising 30 proteins that were increased and 36 that were decreased. Twenty-three DEPs overlapped between Sema/HFD and Empa/HFD, with 11 up-regulated and 12 down-regulated simultaneously. After analysing DEPs in different groups, four proteins -LYVE1, BRAF, RGCC, and CHMP5 -were all downregulated in the HFD group and upregulated by semaglutide and empagliflozin treatment. Conclusion:This study demonstrates that obesity induced by a high-fat diet causes a reduction in the expression of LYVE1, BRAF, RGCC, and CHMP5 proteins, potentially affecting lung function and structure in mice. Significantly, the administration of semaglutide and empagliflozin elevates the levels of these proteins, potentially offering therapeutic benefits against lung injury caused by obesity. Merging semaglutide with empagliflozin may exert a more pronounced impact.

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“…For T2DM patients with concurrent moderate-to-severe chronic kidney disease, 26 weeks of dulaglutide treatment resulted in a 27.7% decrease in UACR ( 24 ). In T2DM patients with a baseline UACR of 135 mg/g, a 26-week semaglutide treatment regimen led to a 14% reduction in UACR ( 25 ). In this study, the baseline UACR in the PEG-Loxe group was 108.5 mg/g, and it decreased by 29.3% after 6 months of treatment, indicating renoprotective effects of PEG-Loxe akin to other GLP-1 RAs.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of polyethylene glycol loxenatide in treating mild-to-moderate diabetic kidney disease in type 2 diabetes patients: a randomized, open-label, clinical trial

Cao,

Zhao

et al. 2024

Front. Endocrinol.

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ObjectiveThis study aimed to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEG-Loxe) compared to those of dapagliflozin in patients with mild-to-moderate diabetic kidney disease (DKD), a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). The study is set against the backdrop of increasing global diabetes incidence and the need for effective DKD management.MethodsThis study constituted a single-center, randomized, open-label, clinical trial. The trial included patients with mild-to-moderate DKD and suboptimal glycemic control. Eligible participants were randomly allocated to one of the two groups for treatment with either PEG-Loxe or dapagliflozin. The primary endpoint was the change in UACR from baseline at 24 weeks.ResultsOverall, 106 patients were randomized and 80 patients completed the study. Following 24 weeks of treatment, the PEG-Loxe group exhibited a mean percent change in baseline UACR of −29.3% (95% confidence interval [CI]: −34.8, −23.7), compared to that of −31.8% in the dapagliflozin group (95% CI: −34.8, −23.7). Both PEG-Loxe and dapagliflozin showed similar efficacy in reducing UACR, with no significant difference between the groups (p = 0.336). The HbA1c levels decreased by −1.30% (95% CI: −1.43, −1.18) in the PEG-Loxe group and by −1.29% (95% CI: −1.42, −1.17) in the dapagliflozin group (p = 0.905). The TG levels decreased by −0.56 mmol/L (95% CI: −0.71, −0.42) in the PEG-Loxe group and −0.33 mmol/L (95% CI: −0.48, −0.19) in the dapagliflozin group (p = 0.023). Differences in TC, HDL-C, LDL-C, SBP, and DBP levels between the groups were not statistically significant (all p > 0.05). Safety profiles were consistent with previous findings, with gastrointestinal adverse events being more common in the PEG-Loxe group.ConclusionsPEG-Loxe is as effective as dapagliflozin in improving urine protein levels in patients with mild-to-moderate DKD and offers superior benefits in improving lipid profiles. These findings support the use of PEG-Loxe in DKD management, contributing to evidence-based treatment options.Clinical Trial Registrationwww.chictr.org.cn, identifier ChiCTR2300070919.

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Albuminuria‐lowering effect of adding semaglutide on top of empagliflozin in individuals with type 2 diabetes: A randomized and placebo‐controlled study

Cited by 10 publications

References 47 publications

Separate and combined effects of empagliflozin and semaglutide on vascular function: A 32‐week randomized trial

Separate and combined effects of empagliflozin and semaglutide on vascular function: A 32‐week randomized trial

Effect of Semaglutide and Empagliflozin on Pulmonary Structure and Proteomics in Obese Mice

Efficacy and safety of polyethylene glycol loxenatide in treating mild-to-moderate diabetic kidney disease in type 2 diabetes patients: a randomized, open-label, clinical trial

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