Effects of once-weekly subcutaneous semaglutide on kidney function and safety in patients with type 2 diabetes: a post-hoc analysis of the SUSTAIN 1–7 randomised controlled trials

Mann, Johannes F.E.; Hansen, Thomas K.; Idorn, Thomas; Leiter, Lawrence A.; Marso, Steven P.; Rossing, Peter; Seufert, Jochen; Tadayon, Sayeh; Vilsbøll, Tina

doi:10.1016/s2213-8587(20)30313-2

Cited by 113 publications

(90 citation statements)

References 32 publications

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“…Moreover, the present study also revealed that semaglutide had a neutral effect on the occurrence of 241 other kinds of SAEs including renal SAEs. Similarly, a recent study [23] based on a post-hoc analysis of the SUSTAIN 1-7 trials suggests no increase in the risk of kidney adverse events with semaglutide. Since semaglutide was observed to increase the risk of both diarrhoea and deep vein thrombosis in this metaanalysis, and diarrhoea or dehydration can lead to the increase in blood viscosity, semaglutide increases the risk of deep vein thrombosis possibly due to increasing that of diarrhoea.…”

Section: Discussionmentioning

confidence: 94%

Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials

et al. 2021

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The PIONEER and SUSTAIN serial trials are designed to assess the efficacy outcomes with semaglutide in patients with type 2 diabetes, but are not powered to assess various safety outcomes. We sought to assess the risk of semaglutide in leading to various serious adverse events (SAEs) in patients with type 2 diabetes. Studies eligible for inclusion were the PIONEER and SUSTAIN trials of semaglutide. We conducted meta-analysis to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Meta-analysis was performed using both random-effects and fixed-effects model to evaluate the robustness of pooled results. We implemented subgroup analysis according to drug dosages and routes of administration and type of comparators. Twenty-one trials were included. Semaglutide versus control significantly reduced total SAEs (RR 0.92, 95% CI 0.87-0.97; I 2 = 0) and atrial fibrillation (RR 0.69, 95% CI 0.50-0.95; I 2 = 0), but significantly increased deep vein thrombosis (RR 3.66, 95% CI 1.09-12.25; I 2 = 0) and diarrhoea (RR 2.66, 95% CI 1.19-5.95; I 2 = 0). Semaglutide had no significant effects on 248 other kinds of SAEs. No statistically significant subgroup effects were observed. Semaglutide has a good safety profile in general and reduces atrial fibrillation by 31%, but increases diarrhoea by 166% and deep vein thrombosis by 266%. These findings may guide that semaglutide should be preferred or avoided in T2D patients with specific susceptibility factors.

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Section: Discussionmentioning

confidence: 94%

Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials

et al. 2021

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“…In SUSTAIN 1-5 and 7, this effect was accompanied by an overall reduction in eGFR, whilst in SUSTAIN 6, no difference was observed. In addition, the albuminuria-lowering effects were higher in patients with either microalbuminuria or macro albuminuria in the semaglutide or active-comparator treatment groups, while no effect was observed in the normo-albuminuria group [111]. These findings are likely limited by a short follow-up.…”

Section: Proteinuria Reduction and Cardiovascular Prevention In T2dm:mentioning

confidence: 80%

Role of Albuminuria in Detecting Cardio-Renal Risk and Outcome in Diabetic Subjects

et al. 2021

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The clinical significance of albuminuria in diabetic subjects and the impact of its reduction on the main cardiorenal outcomes by different drug classes are among the most interesting research focuses of recent years. Although nephrologists and cardiologists have been paying attention to the study of proteinuria for years, currently among diabetics, increased urine albumin excretion ascertains the highest cardio-renal risk. In fact, diabetes is a condition by itself associated with a high-risk of both micro/macrovascular complications. Moreover, proteinuria reduction in diabetic subjects by several treatments lowers both renal and cardiovascular disease progression. The 2019 joint ESC-EASD guidelines on diabetes, prediabetes and cardiovascular (CV) disease assign to proteinuria a crucial role in defining CV risk level in the diabetic patient. In fact, proteinuria by itself allows the diabetic patient to be staged at very high CV risk, thus affecting the choice of anti-hyperglycemic drug class. The purpose of this review is to present a clear update on the role of albuminuria as a cardio-renal risk marker, starting from pathophysiological mechanisms in support of this role. Besides this, we will show the prognostic value in observational studies, as well as randomized clinical trials (RCTs) demonstrating the potential improvement of cardio-renal outcomes in diabetic patients by reducing proteinuria.

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“…Mann et al 2 . published an article, “Effects of once‐weekly subcutaneous semaglutide on kidney function and safety in patients with type 2 diabetes: a post‐hoc analysis of the SUSTAIN 1–7 randomised controlled trials”’ in The Lancet Diabetes & Endocrinology in November 2020.…”

Section: Sustain 1‐5 and Sustain 7 Sustain 6 Semaglutide 05 Mg (N = 1332) Semaglutide 10 Mg (N = 1734) Placebo (N = 262) Sitagliptin 100 mentioning

confidence: 99%

“…Mann et al 2 published an article, "Effects of once-weekly subcutaneous semaglutide on kidney function and safety in patients with type 2 diabetes: a post-hoc analysis of the SUSTAIN 1-7 randomised controlled trials"' in The Lancet Diabetes & Endocrinology in November 2020. They carried out a posthoc analysis of type 2 diabetes patients enrolled in Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) 1-7 trials, to investigate the effects of once-weekly subcutaneous semaglutide 0.5 and 1.0 mg versus comparators on kidney function and safety.…”

mentioning

confidence: 99%

Effects of glucagon‐like peptide‐1 receptor agonists on kidney function and safety in type 2 diabetes patients

Kim

2021

J of Diabetes Invest

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Effects of once-weekly subcutaneous semaglutide on kidney function and safety in patients with type 2 diabetes: a post-hoc analysis of the SUSTAIN 1–7 randomised controlled trials

Cited by 113 publications

References 32 publications

Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials

Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials

Role of Albuminuria in Detecting Cardio-Renal Risk and Outcome in Diabetic Subjects

Effects of glucagon‐like peptide‐1 receptor agonists on kidney function and safety in type 2 diabetes patients

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