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Is there a role for glucagon-like peptide-1 receptor agonists in the management of diabetic nephropathy?

ABSTRACT: Chronic kidney disease constitutes a major microvascular complication of diabetes mellitus. Accumulating data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) might have a role in the management of diabetic kidney disease (DKD). GLP-1 RAs appear to reduce the incidence of persistent macro-albuminuria in patients with type 2 diabetes mellitus. This beneficial effect appears to be mediated not only by the glucose-lowering action of these agents but also on their blood pressure lowering, anti-inflammatory and antioxidant effects. On the other hand, GLP-1 RAs do not appear to affect the rate of decline of glomerular filtration rate. However, this might be due to the relatively short duration of the trials that evaluated their effects on DKD. Moreover, these trials were not designed nor powered to assess renal outcomes. Given than macrolbuminuria is a strong risk factor for the progression of DKD, it might be expected that GLP-1 RAs will prevent the deterioration in renal function in the long term. Nevertheless, this remains to be shown in appropriately designed randomized controlled trials in patients with DKD.

SUBMITTER: Veneti S

PROVIDER: S-EPMC7503505 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Is there a role for glucagon-like peptide-1 receptor agonists in the management of diabetic nephropathy?

Veneti Stavroula S Tziomalos Konstantinos K

World journal of diabetes 20200901 9

Chronic kidney disease constitutes a major microvascular complication of diabetes mellitus. Accumulating data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) might have a role in the management of diabetic kidney disease (DKD). GLP-1 RAs appear to reduce the incidence of persistent macro-albuminuria in patients with type 2 diabetes mellitus. This beneficial effect appears to be mediated not only by the glucose-lowering action of these agents but also on their blood pressure lo ...[more]

PMID: 32994865

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Project description:Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have emerged as promising therapeutic agents with potent anti-inflammatory properties and diverse clinical implications. This in-depth review article explores the mechanisms behind the anti-inflammatory actions of GLP-1RAs and assesses their prospective applicability in a wide range of disease scenarios. The current review establishes the significance of comprehending the anti-inflammatory role of GLP-1RAs and identifies pertinent research gaps. A concise overview of inflammation and its clinical consequences underscores the critical need for effective anti-inflammatory interventions. Subsequently, the article elucidates the intricate mechanisms through which GLP-1RAs modulate immune cell signaling and regulate the nuclear factor-kappa B (NF-κB) pathway. Detailed discussions encompass their impact on inflammatory responses, cytokine production, and attenuation of oxidative stress. The exposition is substantiated by a collection of pertinent examples and an extensive array of references from both preclinical and clinical investigations. The historical trajectory of GLP-1RA drugs, including exenatide, lixisenatide, liraglutide, and semaglutide, is traced to delineate their development as therapeutic agents. Moreover, the review emphasizes the therapeutic potential of GLP-1RAs in specific disease contexts like type 2 diabetes, a neurodegenerative disorder, and inflammatory bowel disease (IBD), shedding light on their anti-inflammatory effects through rigorous examination of preclinical and clinical studies. The article also provides an outlook on future perspectives for GLP-1RAs, encompassing the domains of diabetes, neurodegenerative diseases, and IBD. In conclusion, GLP-1RAs exhibit substantial anti-inflammatory effects, rendering them promising therapeutic agents with broad clinical implications. They are very useful in a wide variety of diseases because they regulate immunological responses, block NF-κB activation, and decrease production of pro-inflammatory cytokines. Ongoing research endeavors aim to optimize their therapeutic use, delineate patient-specific treatment paradigms, and explore novel therapeutic applications. GLP-1RAs represent a significant breakthrough in anti-inflammatory therapy, offering novel treatment options, and improved patient outcomes.

Project description:ObjectiveThe potential association between diabetic retinopathy (DR) worsening and glucagon-like peptide-1 receptor agonists (GLP-1RA) has affected therapeutic management of diabetic patients but remains controversial. This study compared rates of DR development or progression in patients on GLP-1RA to those on SGLT-2 inhibitors (SGLT-2I).DesignRetrospective cohort study.SubjectsNine hundred eighty-one patients with diabetes mellitus taking GLP-1RA or SGLT-2I, the latter serving as controls, between 2012 and 2023.MethodsPatients were one-to-one greedy matched by propensity scores on race/ethnicity, age, smoking status, baseline body mass index and hemoglobin A1c %, type of diabetes mellitus, baseline DR status and history of DR procedures, duration of drug use, whether they had taken both drug types, and change in hemoglobin A1c % after 1 year on the drug.Main outcome measuresThe primary outcome was clinical DR development or progression (termed "worsening") detected by International Classification of Diseases (ICD), 10th edition codes, confirmed by manual review, on GLP-1RA compared with SGLT-2I after propensity score matching. Secondary outcomes included DR worsening indicated by need for procedures due to complications, and time-to-first DR worsening event.ResultsThe study included 692 GLP-1RA users and 289 SGLT-2I users. The mean follow-up periods for GLP-1RA versus SGLT-2I use were 1.54 (standard deviation [SD] 1.82) years and 1.38 (SD 1.56) years, respectively. The rates of clinical worsening were 2.3% and 2.8%, respectively. After propensity score matching, an association was not identified between GLP1-RA and DR worsening neither clinically by ICD-10 codes (odds ratio [OR] = 0.33, 95% confidence interval [CI]: 0.11-1.03) nor by indication for procedures (OR = 0.50, 95% CI 0.13-2.00). Time-to-first DR worsening did not differ between the groups in Kaplan-Meier analysis. The most common type of clinical worsening event for both drug types was vitreous hemorrhage (43.7% and 50% of worsening events in GLP-1RA and SGLT-2I users, respectively). The most common DR procedure indicated was anti-VEGF injections (34% and 35% of GLP-1RA and SGLT-2I events, respectively).ConclusionsDiabetic retinopathy worsening, either clinically or by procedures, was not associated with GLP-1RA compared with SGLT-2I, both before and after propensity score matching on all analyses, including time-to-first worsening event.Financial disclosuresProprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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Is there a role for glucagon-like peptide-1 receptor agonists in the management of diabetic nephropathy?

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Is there a role for glucagon-like peptide-1 receptor agonists in the management of diabetic nephropathy?

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