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UK Kidney Association Clinical Practice Guideline: Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease 2023 UPDATE.

ABSTRACT: Large placebo-controlled trials have demonstrated kidney and cardiovascular clinical benefits of SGLT-2 inhibitors. Data from the EMPA-KIDNEY and DELIVER trials and associated meta-analyses triggered an update to the UK Kidney Association Clinical Practice Guideline on Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease. We provide a summary of the full guideline and highlight the rationale for recent updates. The use of SGLT-2 inhibitors in people with specific medical conditions, including type 1 diabetes, kidney transplants, and people admitted to hospital with heart failure is also considered, along with Recommendations for future research and Recommendations for implementation. A full "lay" summary of the guidelines is provided as an appendix to ensure that these guidelines are accessible and understandable to people who are not medical professionals.

SUBMITTER: Roddick AJ

PROVIDER: S-EPMC10598949 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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UK Kidney Association Clinical Practice Guideline: Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease 2023 UPDATE.

Roddick Alistair J AJ Wonnacott Alexa A Webb David D Watt Angela A Watson Michael A MA Staplin Natalie N Riding Alex A Lioudaki Eirini E Kuverji Apexa A Kossi Mohsen El ME Holmes Patrick P Holloway Matt M Fraser Donald D Carvalho Chris C Burton James O JO Bhandari Sunil S Herrington William G WG Frankel Andrew H AH

BMC nephrology 20231025 1

Large placebo-controlled trials have demonstrated kidney and cardiovascular clinical benefits of SGLT-2 inhibitors. Data from the EMPA-KIDNEY and DELIVER trials and associated meta-analyses triggered an update to the UK Kidney Association Clinical Practice Guideline on Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease. We provide a summary of the full guideline and highlight the rationale for recent updates. The use of SGLT-2 inhibitors in people with specific med ...[more]

PMID: 37880609

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Project description:BackgroundIn Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased quality of life and loss of autonomy. This guideline update is intended to assist Canadian health care professionals in the delivery of care to optimize skeletal health and prevent fractures in postmenopausal females and in males aged 50 years and older.MethodsThis guideline is an update of the 2010 Osteoporosis Canada clinical practice guideline on the diagnosis and management of osteoporosis in Canada. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and quality assurance as per Appraisal of Guidelines for Research and Evaluation (AGREE II) quality and reporting standards. Primary care physicians and patient partners were represented at all levels of the guideline committees and groups, and participated throughout the entire process to ensure relevance to target users. The process for managing competing interests was developed before and continued throughout the guideline development, informed by the Guideline International Network principles. We considered benefits and harms, patient values and preferences, resources, equity, acceptability and feasibility when developing recommendations; the strength of each recommendation was assigned according to the GRADE framework.RecommendationsThe 25 recommendations and 10 good practice statements are grouped under the sections of exercise, nutrition, fracture risk assessment and treatment initiation, pharmacologic interventions, duration and sequence of therapy, and monitoring. The management of osteoporosis should be guided by the patient's risk of fracture, based on clinical assessment and using a validated fracture risk assessment tool. Exercise, nutrition and pharmacotherapy are key elements of the management strategy for fracture prevention and should be individualized.InterpretationThe aim of this guideline is to empower health care professionals and patients to have meaningful discussions on the importance of skeletal health and fracture risk throughout older adulthood. Identification and appropriate management of skeletal fragility can reduce fractures, and preserve mobility, autonomy and quality of life.

Project description:Purpose In 2016, ASCO published a guideline to assist in clinical decision making in metastatic pancreatic cancer for initial assessment after diagnosis, first- and second-line treatment options, palliative and supportive care, and follow-up. The purpose of this update is to incorporate new evidence related to second-line therapy for patients who have experienced disease progression or intolerable toxicity during first-line therapy. Methods ASCO convened an Expert Panel to conduct a systematic review of the literature on second-line therapy published between June 2015 and January 2018. Recommendations on other topics covered in the 2016 Metastatic Pancreatic Cancer Guideline were endorsed by the Expert Panel. Results Two new studies were found that met the inclusion criteria. Recommendations For second-line therapy, gemcitabine plus nanoparticle albumin-bound paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin), an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1, and a favorable comorbidity profile; fluorouracil plus nanoliposomal irinotecan can be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, an ECOG PS of 0 to 1, and a favorable comorbidity profile; fluorouracil plus irinotecan or fluorouracil plus oxaliplatin may be offered when there is a lack of availability of fluorouracil plus nanoliposomal irinotecan; gemcitabine or fluorouracil should be offered to patients with either an ECOG PS of 2 or a comorbidity profile that precludes other regimens. Testing select patients for mismatch repair deficiency or microsatellite instability is recommended, and pembrolizumab is recommended for patients with mismatch repair deficiency or high microsatellite instability tumors. Endorsed recommendations from the 2016 version of this guideline for computed tomography, baseline performance status and comorbidity profile, defining goals of care, first-line therapy, and palliative care are also contained within the full guideline text. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

Project description:Aims: This study aimed to investigate the association between the use of sodium-glucose transporter 2 inhibitors (SGLT-2i) and the risk of diabetic ketoacidosis (DKA), lower limb amputation (LLA), urinary tract infections (UTI), genital tract infections (GTI), bone fracture, and hypoglycemia in cohort studies. Methods: A systematic search was conducted in the PubMed and Embase databases to identify cohort studies comparing the safety of SGLT-2i versus other glucose-lowering drugs (oGLD) in patients with type 2 diabetes mellitus (T2DM). The quality of the studies was assessed using the Newcastle-Ottawa Scale. Primary endpoints were DKA and LLA, while secondary endpoints included UTI, GTI, bone fracture, and hypoglycemia. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Results: A total of 9,911,454 patients from 40 cohort studies were included in the analysis. SGLT-2i use was associated with a higher risk of DKA (HR: 1.21, 95% CI: 1.07-1.38, p = 0.003) and GTI (HR: 2.72, 95% CI: 2.48-2.98, p < 0.01). However, it was not associated with an increased risk of LLA (HR: 1.06, 95% CI: 0.92-1.23, p = 0.42), UTI (HR: 0.99, 95% CI: 0.89-1.10, p = 0.83), or bone fracture (HR: 0.99, 95% CI: 0.94-1.04, p = 0.66). Furthermore, SGLT-2i was associated with a reduced risk of hypoglycemia. Furthermore, compared to dipeptidyl peptidase 4 inhibitors, SGLT-2i as a class and individually was associated with an increased risk of DKA. Canagliflozin specifically increased the risk of LLA (HR: 1.19, 95% CI: 1.04-1.36, p = 0.01). The subgroup analysis suggested that SGLT-2i increased the risk of LLA among patients with a history of cardiovascular disease. Conclusion: SGLT-2i versus oGLD was associated with a similar occurrence of LLA, UTI, and bone fracture. However, SGLT-2i was associated with a higher risk of DKA and GTI than oGLD. These findings provide valuable information on the safety profile of SGLT-2i in patients with T2DM and can help inform clinical decision-making.

Project description:A current trend in the quest for new therapies for complex, multifactorial diseases, such as diabetes mellitus (DM), is to find dual or even multi-target inhibitors. In DM, the sodium dependent glucose cotransporter 2 (SGLT2) in the kidneys and the glycogen phosphorylase (GP) in the liver are validated targets. Several (β-D-glucopyranosylaryl)methyl (het)arene type compounds, called gliflozins, are marketed drugs that target SGLT2. For GP, low nanomolar glucose analogue inhibitors exist. The purpose of this study was to identify dual acting compounds which inhibit both SGLTs and GP. To this end, we have extended the structure-activity relationships of SGLT2 and GP inhibitors to scarcely known (C-β-D-glucopyranosylhetaryl)methyl arene type compounds and studied several (C-β-D-glucopyranosylhetaryl)arene type GP inhibitors against SGLT. New compounds, such as 5-arylmethyl-3-(β-D-glucopyranosyl)-1,2,4-oxadiazoles, 5-arylmethyl-2-(β-D-glucopyranosyl)-1,3,4-oxadiazoles, 4-arylmethyl-2-(β-D-glucopyranosyl)pyrimidines and 4(5)-benzyl-2-(β-D-glucopyranosyl)imidazole were prepared by adapting our previous synthetic methods. None of the studied compounds exhibited cytotoxicity and all of them were assayed for their SGLT1 and 2 inhibitory potentials in a SGLT-overexpressing TSA201 cell system. GP inhibition was also determined by known methods. Several newly synthesized (C-β-D-glucopyranosylhetaryl)methyl arene derivatives had low micromolar SGLT2 inhibitory activity; however, none of these compounds inhibited GP. On the other hand, several (C-β-D-glucopyranosylhetaryl)arene type GP inhibitor compounds with low micromolar efficacy against SGLT2 were identified. The best dual inhibitor, 2-(β-D-glucopyranosyl)-4(5)-(2-naphthyl)-imidazole, had a Ki of 31 nM for GP and IC50 of 3.5 μM for SGLT2. This first example of an SGLT-GP dual inhibitor can prospectively be developed into even more efficient dual-target compounds with potential applications in future antidiabetic therapy.

Dataset Information

UK Kidney Association Clinical Practice Guideline: Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease 2023 UPDATE.

Publications

UK Kidney Association Clinical Practice Guideline: Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease 2023 UPDATE.

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