The effect of liraglutide on renal function: A randomized clinical trial

Scholten, Bernt Johan von; Persson, Frederik; Rosenlund, Signe; Hovind, Peter; Faber, Jens; Hansen, Tine W.; Rossing, Peter

doi:10.1111/dom.12808

Cited by 85 publications

(103 citation statements)

References 32 publications

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“…This is in line with the presence of GLP‐1 receptors demonstrated on monocytes/macrophages and supports the reported 12% reduction of TNF‐α in liraglutide treated patients with type 2 diabetes and microalbuminuria . The shown reduction of microalbuminuria in the liraglutide treated group is in accordance with previous data from the larger outcome studies . In addition, recent findings advocate that the IL‐6 pathway seems overactive in 40% of type 1 diabetes patients and that this previously has been implicated in the initiation and progression of microalbuminuria .…”

Section: Discussionsupporting

confidence: 89%

Liraglutide treatment reduced interleukin‐6 in adults with type 1 diabetes but did not improve established autonomic or polyneuropathy

Brock

Hansen

Karmisholt

et al. 2019

Brit J Clinical Pharma

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AimsType 1 diabetes can be complicated with neuropathy that involves immune‐mediated and inflammatory pathways. Glucagon‐like peptide‐1 receptor agonists such as liraglutide, have shown anti‐inflammatory properties, and thus we hypothesized that long‐term treatment with liraglutide induced diminished inflammation and thus improved neuronal function.MethodsThe study was a randomized, double‐blinded, placebo‐controlled trial of adults with type 1 diabetes and confirmed symmetrical polyneuropathy. They were randomly assigned (1:1) to receive either liraglutide or placebo. Titration was 6 weeks to 1.2–1.8 mg/d, continuing for 26 weeks. The primary endpoint was change in latency of early brain evoked potentials. Secondary endpoints were changes in proinflammatory cytokines, cortical evoked potential, autonomic function and peripheral neurophysiological testing.ResultsThirty‐nine patients completed the study, of whom 19 received liraglutide. In comparison to placebo, liraglutide reduced interleukin‐6 (−22.6%; 95% confidence interval [CI]: −38.1, −3.2; P = .025) with concomitant numerical reductions in other proinflammatory cytokines. However neuronal function was unaltered at the central, autonomic or peripheral level. Treatment was associated with −3.38 kg (95% CI: −5.29, −1.48; P < .001] weight loss and a decrease in urine albumin/creatinine ratio (−40.2%; 95% CI: −60.6, −9.5; P = .02).ConclusionHitherto, diabetic neuropathy has no cure. Speculations can be raised whether mechanism targeted treatment, e.g. lowering the systemic level of proinflammatory cytokines may lead to prevention or treatment of the neuroinflammatory component in early stages of diabetic neuropathy. If ever successful, this would serve as an example of how fundamental mechanistic principles are translated into clinical practice similar to those applied in the cardiovascular and nephrological clinic.

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Section: Discussionsupporting

confidence: 89%

Liraglutide treatment reduced interleukin‐6 in adults with type 1 diabetes but did not improve established autonomic or polyneuropathy

Brock

Hansen

Karmisholt

et al. 2019

Brit J Clinical Pharma

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“…Studies have reported that GLP-1 receptor agonists have nephroprotective effects, which are independent of the glucose-lowering effects (14,15). Liraglutide has been reported to decrease proteinuria and attenuate the progression of renal dysfunction (16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

Effects of Once-Weekly Dulaglutide on Glycemic Control and Renal Function in Patients with Advanced-Stage Diabetic Nephropathy

et al. 2017

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Objectives: Dulaglutide and liraglutide are glucagon-like peptide-1 receptor agonists. We investigated the effects of once-weekly dulaglutide on glycemic control and renal function compared to once-daily liraglutide in patients with advanced-stage diabetic nephropathy. Methods: Changes over a 12-month period in levels of glycated hemoglobin, urine protein/creatinine ratio, and annual change in estimated glomerular filtration rate were retrospectively analyzed in 10 patients with advanced-stage diabetic nephropathy after changing from once-daily liraglutide (0.9 mg/day) to once-weekly dulaglutide (0.75 mg/week) (dulaglutide group). The control group comprised 10 patients with advanced-stage diabetic nephropathy who had continued once-daily liraglutide (0.9 mg/day) (liraglutide group). Results: The glycated hemoglobin level significantly decreased in the dulaglutide group after switching from liraglutide to dulaglutide (-0.81 ± 1.03% at 12 months from baseline, P < 0.05), but no change occurred in the liraglutide group. The urine protein/creatinine ratio and annual change in estimated glomerular filtration rate did not change in either groups. Conclusions: Once-weekly dulaglutide may be more advantageous for glycemic control compared to once-daily liraglutide in patients with advanced-stage diabetic nephropathy.

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“…In a small study including twenty-three type 2 diabetic patients with diabetic nephropathy, treatment with liraglutide for twelve months on top of rennin-angiotensin system blockers led to a significant reduction in HbA1c, proteinuria and counteracted the progression of diabetic R8 Review a a hasan and b hocher Role of DPP-4 in diabetic nephropathy 59 1 : R8 Review nephropathy as indicated by decreasing the rate of decline in eGFR (Imamura et al 2013). Also, another small placebo-controlled randomized trial reported that liraglutide was able to show renal beneficial effects in terms of reduction of urinary albumin excretion in type 2 diabetic patients with albuminuria (von Scholten et al 2016). Moreover, eGFR was not affected but UACR was decreased by dulaglutide treatment in 6005 type 2 diabetic patients (Tuttle et al 2016).…”

Section: Glp-1mentioning

confidence: 99%

Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy

Hasan

Hocher

2017

Journal of Molecular Endocrinology

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Diabetic nephropathy is one of the most frequent, devastating and costly complications of diabetes. The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might also have reno-protective properties. DPP-4 exists in two forms: a plasma membranebound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians. DPP-4 expression and urinary activity are up-regulated in diabetic nephropathy, highlighting its role as a potential target to manage diabetic nephropathy. Preclinical animal studies and some clinical data suggest that DPP-4 inhibitors decrease the progression of diabetic nephropathy in a blood pressure-and glucose-independent manner. Many studies reported that these reno-protective effects could be due to increased half-life of DPP-4 substrates such as glucagon-like peptide-1 (GLP-1) and stromal derived factor-1 alpha (SDF-1a). However, the underlying mechanisms are far from being completely understood and clearly need further investigations.

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The effect of liraglutide on renal function: A randomized clinical trial

Abstract: Our placebo-controlled randomized trial suggests that liraglutide has renoprotective effects on top of multifactorial treatment, including RAS-inhibition, in patients with type 2 diabetes and albuminuria.

Cited by 85 publications

References 32 publications

Liraglutide treatment reduced interleukin‐6 in adults with type 1 diabetes but did not improve established autonomic or polyneuropathy

Liraglutide treatment reduced interleukin‐6 in adults with type 1 diabetes but did not improve established autonomic or polyneuropathy

Effects of Once-Weekly Dulaglutide on Glycemic Control and Renal Function in Patients with Advanced-Stage Diabetic Nephropathy

Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy

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