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  5. 近五年2型糖尿病合并CKD指南：SGLT2i、GLP-1RA、ns-MRA推荐变迁

近五年2型糖尿病合并CKD指南：SGLT2i、GLP-1RA、ns-MRA推荐变迁

文献检索Suppr助手发表于 2026年05月20日 11:4014阅读
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近五年 2 型糖尿病合并慢性肾病指南/共识中，SGLT2 抑制剂、GLP-1RA、非甾体 MRA 的推荐位置有什么变化？请按年份、机构、推荐等级和证据依据整理。

近年来，2型糖尿病（T2D）合并慢性肾病（CKD）患者的治疗指南和共识发生了显著变化，主要体现在对钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）、胰高糖素样肽-1受体激动剂（GLP-1RA）和非甾体盐皮质激素受体拮抗剂（ns-MRA）的推荐位置上。这些变化主要受到多项临床试验的积极结果以及对心肾保护重要性的日益认识所驱动。

以下是对近五年（2019-2024）相关指南和共识中SGLT2i、GLP-1RA和ns-MRA推荐位置变化的总结，按年份、机构、推荐等级和证据依据进行整理：

2019年及以前

在2019年，美国糖尿病协会（ADA）、欧洲糖尿病研究协会（EASD）和欧洲心脏病学会（ESC）已经发布了更新的T2D患者管理建议，这些建议强调了GLP-1RA和SGLT2i在减少心肾事件方面的有效性，尤其是在高心血管风险的T2D患者中。这些药物从单纯的降糖药物演变为心肾代谢治疗药物，体现了治疗理念的转变。

2020年

  • 机构： 肾脏疾病：改善全球结局组织（KDIGO）
  • 指南/共识： KDIGO 2020糖尿病合并CKD临床实践指南（此为2022年更新的基础）
  • SGLT2i推荐： 2020年的KDIGO指南已包含SGLT2i的相关推荐，主要基于其在改善肾脏和心血管结局方面的证据。
  • GLP-1RA推荐： GLP-1RA也已在2020年指南中占据一席之地，强调其心血管益处。
  • ns-MRA推荐： Finerenone作为首个非甾体MRA，尚未在2020年指南中获得明确推荐，因为当时缺乏足够大规模的临床试验数据。
  • 证据依据： 主要是针对SGLT2i和GLP-1RA的心血管结局试验（CVOTs）结果，显示它们能够降低全因死亡率、心血管死亡率、非致死性心肌梗死和肾衰竭（高级别证据）。SGLT2i在降低心力衰竭住院方面优于GLP-1RA，而GLP-1RA在降低非致死性卒中方面优于SGLT2i。

2021年

  • 机构： 美国糖尿病协会（ADA）
  • 指南/共识： 2021年ADA糖尿病医疗标准
  • SGLT2i/GLP-1RA推荐： ADA的建议指出，约三分之一的初级保健T2D患者根据2021年ADA的严格共病定义，符合SGLT2i或GLP-1RA的用药标准，这包括心力衰竭、蛋白尿性CKD或动脉粥样硬化性心血管疾病（ASCVD）。
  • 证据依据： 严格的共病定义，例如根据心力衰竭或蛋白尿性CKD，13%的患者符合SGLT2i标准；根据ASCVD或白蛋白与肌酐比值≤300 mg/g的CKD，18%的患者符合其中任一药物的标准。

2022年

这一年是糖尿病合并CKD管理指南更新的关键一年，多个重要机构发布了新指南或共识。

  • 机构： 美国糖尿病协会（ADA）和肾脏疾病：改善全球结局组织（KDIGO）

  • 指南/共识： ADA和KDIGO联合发布的《糖尿病合并CKD管理共识报告》。

  • SGLT2i、GLP-1RA、ns-MRA推荐： 该报告强调了综合治疗，将SGLT2i、GLP-1RA和ns-MRA等药物作为健康生活方式基础上的药物治疗，并明确指出这些药物已被证实可改善肾脏和心血管结局。共识声明为这些药物的使用提供了具体指导。

  • 推荐等级： 具体推荐等级需参考原报告，但共识报告表明这些药物的地位得到显著提升。

  • 证据依据： 大量临床试验支持新的糖尿病合并CKD治疗方法。这些指南与CKD筛查和诊断、血糖监测、生活方式疗法、治疗目标以及药物管理领域保持一致。

  • 机构： 肾脏疾病：改善全球结局组织（KDIGO）

  • 指南/共识： KDIGO 2022年糖尿病合并CKD临床实践指南更新。

  • SGLT2i推荐： SGLT2i被推荐作为一线药物，用于改善临床结局，并且其在肾功能方面的应用范围扩大，起始使用时估计肾小球滤过率（eGFR）≥20 mL/min/1.73m²。在CKD患者中，SGLT2i能显著降低全因死亡、心血管死亡、心力衰竭住院和终末期肾病（高级别证据）。

  • GLP-1RA推荐： GLP-1RA被推荐作为具有心脏和肾脏保护作用的附加药物，尤其是在心血管结局方面表现出色，包括降低非致死性卒中。

  • ns-MRA（Finerenone）推荐： Finerenone被添加为首个经FDA批准的非甾体MRA，用于降低心肾终点事件。在CKD患者中，Finerenone可能降低住院心力衰竭和终末期肾病，并可能降低心血管死亡（中等确定性证据）。

  • 推荐等级：

    • SGLT2i作为一线药物，具有强烈的推荐。
    • GLP-1RA和ns-MRA作为附加药物，也具有明确的推荐。

  • 证据依据： 此次快速更新反映了近期众多临床试验在减少糖尿病患者肾脏和心血管发病率及死亡率方面取得的前所未有的积极结果。特别是在心血管和肾脏结局试验中，SGLT2i和GLP-1RA的益处得到进一步确认，包括对不同亚组的评估。Finerenone的加入也基于其在伴有CKD的T2D患者中延缓糖尿病肾病进展和降低心力衰竭住院的证据。

  • 机构： 美国糖尿病协会（ADA）和欧洲糖尿病研究协会（EASD）

  • 指南/共识： 2022年成人2型糖尿病高血糖管理共识报告。

  • SGLT2i/GLP-1RA推荐： 该报告进一步强调了SGLT2i和GLP-1RA在心肾保护方面的广泛推荐，尤其是在高心肾疾病风险的糖尿病患者中。

  • 证据依据： 2018年以来的系统性文献审查，特别是SGLT2i和GLP-1RA的心血管和肾脏结局试验结果，包括对亚组的评估。

  • 机构： BMJ（英国医学杂志）系统评价和网络荟萃分析

  • 指南/共识： 《2型糖尿病药物治疗的益处和危害：随机对照试验的系统评价和网络荟萃分析》。

  • SGLT2i推荐： 确认了SGLT2i在降低心血管死亡、非致死性心肌梗死、心力衰竭住院和终末期肾病方面的益处（高级别确定性）。SGLT2i在降低终末期肾病方面优于其他药物。

  • GLP-1RA推荐： 确认了GLP-1RA在降低心血管死亡、非致死性心肌梗死和终末期肾病方面的益处（高级别确定性），并且是唯一降低非致死性卒中的药物。

  • ns-MRA（Finerenone）推荐： Finerenone可能降低死亡率（中等确定性），可能降低心力衰竭住院和终末期肾病，以及可能降低心血管死亡。

  • 推荐等级： 高级别确定性（SGLT2i和GLP-1RA的心血管和肾脏益处），中等确定性（Finerenone对死亡率、心力衰竭住院和终末期肾病的益处）。

  • 证据依据： 涵盖了816项试验，471,038名患者，评估了13种不同药物类别，并使用了GRADE方法评估证据确定性。

2023年

  • 机构： 欧洲心脏病学会（ESC）

  • 指南/共识： 2023年ESC糖尿病合并T2D患者心血管疾病管理指南。

  • SGLT2i/GLP-1RA推荐： 首次明确推荐SGLT2i和GLP-1RA作为一线疗法，用于降低ASCVD、心力衰竭和CKD患者或高风险患者的心血管风险。

  • ns-MRA（Finerenone）推荐： Finerenone已被2023年ESC指南推荐用于T2D合并CKD患者的糖尿病管理，因为它已被证明能延缓糖尿病肾病进展并降低心力衰竭住院率。

  • 推荐等级： 强推荐（SGLT2i和GLP-1RA作为一线疗法），明确推荐（Finerenone）。

  • 证据依据： 多项里程碑式的抗高血糖药物心血管结局试验结果。

  • 机构： KDIGO（争议会议结论）

  • 指南/共识： 肾脏疾病和心力衰竭：最新进展和当前挑战（2024年3月KDIGO争议会议结论，2023年发表）。

  • SGLT2i、RAAS抑制剂、Finerenone、GLP-1RA推荐： 讨论强调这些药物对心力衰竭和CKD患者均有益处，但晚期CKD患者的证据有限。

  • 证据依据： 这些药物在两个患者群体中都显示出益处，这表明需要更综合的管理方法，植根于个体化、临床背景和共同的治疗目标。

2024年

  • 机构： BMJ（英国医学杂志）生活系统评价和网络荟萃分析
  • 指南/共识： 《2型糖尿病成人药物：生活系统评价和网络荟萃分析》、《2型糖尿病治疗心血管、肾脏和体重减轻效果：生活临床实践指南》和《钠-葡萄糖共转运蛋白-2（SGLT-2）抑制剂用于慢性肾病成人：临床实践指南》。
  • SGLT2i推荐：
    • 所有CKD成人： 强推荐（高风险和极高风险的CKD患者）和弱推荐（中低风险的CKD患者），无论是否患有T2D，均建议使用SGLT2i来改善肾脏和心血管结局。
    • T2D合并心血管疾病（CVD）、CKD或心力衰竭（HF）高风险患者： 强烈推荐使用SGLT2i。
    • T2D合并CVD和/或CKD中度风险患者： 弱推荐使用SGLT2i。
    • T2D合并低风险患者： 弱推荐不使用SGLT2i。
    • 副作用： SGLT2i增加生殖器感染和糖尿病酮症酸中毒的风险，并可能增加截肢风险（中等确定性）。
  • GLP-1RA推荐：
    • T2D合并心血管疾病（CVD）、CKD或心力衰竭（HF）高风险患者： 强烈推荐使用GLP-1RA。
    • T2D合并CVD和/或CKD中度风险患者： 弱推荐使用GLP-1RA。
    • T2D合并低风险患者： 弱推荐不使用GLP-1RA。
    • 副作用： GLP-1RA可能增加严重的胃肠道事件（中等确定性）。
  • ns-MRA（Finerenone）推荐：
    • T2D合并CKD高风险患者： 弱推荐使用Finerenone。
    • T2D合并CKD中度风险患者： 弱推荐不使用Finerenone。
    • 副作用： Finerenone增加严重高钾血症的风险（高级别确定性）。
  • Tirzepatide（新型GIP/GLP-1RA）：
    • 肥胖成人： 弱推荐使用Tirzepatide。
    • 体重管理： Tirzepatide可能导致最大的体重减轻（中等确定性）。
    • 副作用： Tirzepatide可能增加严重的胃肠道不良事件（中等确定性）。
  • 推荐等级：
    • SGLT2i和GLP-1RA在T2D合并CVD、CKD或HF高风险患者中为“强烈推荐”；在中度风险患者中为“弱推荐”；在低风险患者中为“弱推荐反对”。
    • Finerenone在T2D合并CKD高风险患者中为“弱推荐”；在中度风险患者中为“弱推荐反对”。
    • Tirzepatide在肥胖成人中为“弱推荐”。
  • 证据依据： 基于包含493,168名参与者的869项试验的系统评价和网络荟萃分析，结合GRADE方法，定期更新证据。这些指南考虑了不同风险分层的患者群体，并提供了风险分层推荐，明确区分了不同药物的益处和危害。SGLT2i的益处被认为适用于所有CKD成人，无论是否患有T2D，其强度根据CKD进展和并发症的风险而异。

总结与趋势

从近五年的指南和共识中可以看出以下几个显著变化和趋势：

  1. SGLT2i和GLP-1RA地位的巩固与提升：

    • 这两种药物在T2D合并CKD患者中的推荐已从最初的降糖药物扩展到心肾保护药物，并逐渐成为核心治疗方案。
    • 它们在降低心血管死亡、非致死性心肌梗死、心力衰竭住院和肾衰竭等主要结局方面的益处得到了高级别证据的广泛支持。
    • SGLT2i的适用范围进一步扩大，即使是非T2D的CKD患者，也强烈推荐使用SGLT2i，且起始eGFR阈值降低。
    • GLP-1RA在降低非致死性卒中方面表现出独特的优势。

  2. ns-MRA（Finerenone）的出现和确立：

    • Finerenone作为首个非甾体MRA，在2022年之后被快速纳入指南，成为减少糖尿病合并CKD患者心肾终点事件的新选择。
    • 其在降低心力衰竭住院和终末期肾病方面的益处得到中等确定性证据的支持，并且在T2D合并CKD高风险患者中获得弱推荐。
    • Finerenone与SGLT2i联合使用，可以通过互补机制提供额外保护，并可能有助于减少一些副作用（例如SGLT2i可降低高钾血症风险）。

  3. 组合疗法成为新范式：

    • 最新的证据强调SGLT2i、GLP-1RA和ns-MRA通过互补机制降低代谢、肾脏和心血管风险，支持这些疗法联合使用。
    • 组合疗法不仅提供累加的保护作用，还可能减少副作用，从而实现对个体患者特点和需求的定制治疗。

  4. 风险分层和个体化治疗：

    • 指南越来越强调根据患者的心血管和肾脏结局基线风险进行风险分层，并据此制定个体化的治疗方案。
    • 对于高风险或极高风险的患者，SGLT2i和GLP-1RA的推荐等级更高，通常为强推荐。
    • 活体系统评价和指南的发布，以及交互式决策支持工具的应用，旨在帮助临床医生根据患者的个体风险状况做出更精准的治疗选择。

  5. 对新型药物的关注：

    • Tirzepatide（一种GIP/GLP-1双受体激动剂）因其在体重减轻方面的显著效果和心血管益处，也开始被纳入指南讨论，尤其在肥胖的T2D患者中获得弱推荐。

  6. 实施挑战：

    • 尽管指南推荐不断更新，但在实际临床实践中，特别是在美国，SGLT2i和GLP-1RA的依从性仍面临挑战，如保险覆盖不均和高昂的费用，限制了其在弱势群体的应用，从而可能加剧医疗健康差异。
    • 2018-2020年间，老年T2D患者中指南一致性用药的比例仍然较低，尤其在心肾疾病患者中仅有30%的处方符合指南，这表明在推广新疗法方面仍需努力。

总体而言，近五年T2D合并CKD的指南/共识发生了根本性转变，从单纯的血糖控制转向以心肾保护为核心的综合管理。SGLT2i、GLP-1RA和ns-MRA（finerenone）已成为这一新范式的基石，并且未来的趋势将更加强调组合疗法和基于个体风险分层的精准治疗。

References

1Diabetes Management in Chronic Kidney Disease: A Consensus Report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO).PubMed

Ian H de Boer, Kamlesh Khunti, Tami Sadusky, et al.
People with diabetes and chronic kidney disease (CKD) are at high risk for kidney failure, atherosclerotic cardiovascular disease, heart failure, and premature mortality. Recent clinical trials support new approaches to treat diabetes and CKD. The 2022 American Diabetes Association (ADA) Standards of Medical Care in Diabetes and the Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease each provide evidence-based recommendations for management. A joint group of ADA and KDIGO representatives reviewed and developed a series of consensus statements to guide clinical care from the ADA and KDIGO guidelines. The published guidelines are aligned in the areas of CKD screening and diagnosis, glycemia monitoring, lifestyle therapies, treatment goals, and pharmacologic management. Recommendations include comprehensive care in which pharmacotherapy that is proven to improve kidney and cardiovascular outcomes is layered on a foundation of healthy lifestyle. Consensus statements provide specific guidance on use of renin-angiotensin system inhibitors, metformin, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and a nonsteroidal mineralocorticoid receptor antagonist. These areas of consensus provide clear direction for implementation of care to improve clinical outcomes of people with diabetes and CKD.

2KDOQI Commentary on the KDIGO 2022 Update to the Clinical Practice Guideline for Diabetes Management in CKD.PubMed

Amy K Mottl, Susanne B Nicholas
The Kidney Disease: Improving Global Outcomes (KDIGO) guideline for diabetes management in chronic kidney disease (CKD) was updated in 2022, just 2 years after the previous update. The need for this rapid update is reflective of the recent and unprecedented positive results of numerous clinical trials aimed at reducing kidney and cardiovascular morbidity and mortality in people with diabetes. The Kidney Disease Outcomes Quality Initiative (KDOQI) work group for diabetes in CKD, convened by the National Kidney Foundation, provides herein a commentary on these changes, particularly the implications for health care in the United States. Changes to the KDIGO guideline mirror the evolution of sodium/glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists from purely antihyperglycemic agents to cardiorenal-metabolic therapeutics, and the lower estimated glomerular filtration rate of≥20mL/min/1.73m for SGLT2 inhibitor initiation. New data have also brought the addition of the first-in-class, Federal Drug Administration-approved nonsteroidal mineralocorticoid receptor antagonist finerenone as an agent to reduce cardiorenal end points. While there has been significant progress in innovation, there remain serious challenges to implementation, particularly in the United States where inequities in insurance coverage and high costs limit their use, particularly in vulnerable populations, ultimately widening health care disparities.

3Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).PubMed

Melanie J Davies, Vanita R Aroda, Billy S Collins, et al.
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the previous consensus statements on the management of hyperglycaemia in type 2 diabetes in adults, published since 2006 and last updated in 2019. The target audience is the full spectrum of the professional healthcare team providing diabetes care in the USA and Europe. A systematic examination of publications since 2018 informed new recommendations. These include additional focus on social determinants of health, the healthcare system and physical activity behaviours including sleep. There is a greater emphasis on weight management as part of the holistic approach to diabetes management. The results of cardiovascular and kidney outcomes trials involving sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, including assessment of subgroups, inform broader recommendations for cardiorenal protection in people with diabetes at high risk of cardiorenal disease. After a summary listing of consensus recommendations, practical tips for implementation are provided.

4Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.PubMed

Qingyang Shi, Kailei Nong, Per Olav Vandvik, et al.
OBJECTIVE: To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Ovid Medline, Embase, and Cochrane Central up to 14 October 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach. RESULTS: The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes). CONCLUSIONS: This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022325948.

5Application of 2021 American Diabetes Association Glycemic Treatment Clinical Practice Recommendations in Primary Care.PubMed

Caitlin Colling, Steven J Atlas, Deborah J Wexler
OBJECTIVE: We aimed to identify the proportion of primary care patients meeting criteria for sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) for cardiorenal comorbidities per 2021 American Diabetes Association (ADA) Standards of Care recommendations using readily available electronic health record (EHR) characteristics. RESEARCH DESIGN AND METHODS: We applied 2021 ADA recommendations to a primary care cohort of 13,350 adults with type 2 diabetes (T2D). RESULTS: We found that 33% of patients with diabetes would be eligible for an SGLT2i or GLP-1 RA based on cardiorenal comorbidities, 13% of patients met criteria for an SGLT2i based on heart failure or albuminuric chronic kidney disease (CKD), and 18% of patients met criteria for either agent based on atherosclerotic cardiovascular disease or CKD with an albumin-to-creatinine ratio of ≤300 mg/g. CONCLUSIONS: This EHR algorithm identified one-third of primary care patients with T2D as meeting criteria for SGLT2i and GLP-1 RA based on strict comorbidity definitions according to 2021 ADA recommendations.

6Diabetes Management in Chronic Kidney Disease: Synopsis of the KDIGO 2022 Clinical Practice Guideline Update.PubMed

Sankar D Navaneethan, Sophia Zoungas, M Luiza Caramori, et al.
DESCRIPTION: The KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease is an update of the 2020 guideline from Kidney Disease: Improving Global Outcomes (KDIGO). METHODS: The KDIGO Work Group updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the Work Group used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and expert judgment to develop consensus practice points. New evidence led to updating of recommendations in the chapters Comprehensive Care in Patients With Diabetes and CKD (Chapter 1) and Glucose-Lowering Therapies in Patients With T2D and CKD (Chapter 4). New evidence did not change recommendations in the chapters Glycemic Monitoring and Targets in Patients With Diabetes and CKD (Chapter 2), Lifestyle Interventions in Patients With Diabetes and CKD (Chapter 3), and Approaches to Management of Patients With Diabetes and CKD (Chapter 5). RECOMMENDATIONS: The updated guideline includes 13 recommendations and 52 practice points for clinicians caring for patients with diabetes and chronic kidney disease (CKD). A focus on preserving kidney function and maintaining well-being is recommended using a layered approach to care, starting with a foundation of lifestyle interventions, self-management, and first-line pharmacotherapy (such as sodium-glucose cotransporter-2 inhibitors) demonstrated to improve clinical outcomes. To this are added additional drugs with heart and kidney protection, such as glucagon-like peptide-1 receptor agonists and nonsteroidal mineralocorticoid receptor antagonists, and interventions to control risk factors for CKD progression and cardiovascular events, such as blood pressure, glycemia, and lipids.

7New ways of mitigating aldosterone in cardiorenal disease.PubMed

Felix Götzinger, Michael Kunz, Lucas Lauder, et al.
Steroidal mineralocorticoid receptor antagonists (MRAs) bind to the mineralocorticoid receptor and antagonize the effects of aldosterone, which contributes to the development and progression of cardio- and renovascular diseases. Guidelines recommend steroidal MRAs in patients with heart failure with reduced or mildly reduced ejection fraction, as they reduce morbidity and mortality. In heart failure with preserved ejection fraction, MRAs have not convincingly shown to improve prognosis. Steroidal MRAs delay the progression of chronic kidney disease, reduce proteinuria and lower blood pressure in resistant hypertension but can induce hyperkalaemia. Due to their limited selectivity to the mineralocorticoid receptor, steroidal MRAs can cause significant adverse effects, i.e. libido loss, erectile dysfunction, gynaecomastia, and amenorrhoea, leading to low rates of persistance. Against this background, new avenues for developing non-steroidal, selective (ns)MRAs and aldosterone-synthase inhibitors have been taken. Finerenone has been shown to delay the progression of diabetic nephropathy and lower the incidence of heart failure hospitalizations in patients with chronic kidney disease and diabetes compared with placebo. Finerenone has therefore been recommended by the 2023 European Society of Cardiology Guidelines for the management of diabetes in patients with type 2 diabetes and chronic kidney disease. Further randomized controlled trials assessing the safety and effectiveness of finerenone in patients with heart failure are currently ongoing. Esaxerenone provides antihypertensive effects and has been approved for the treatment of hypertension in Japan. Baxdrostat and lorundostat, novel selective aldosterone-synthase inhibitors, are currently under investigation. In phase II trials, baxdrostat and lorundostat were safe and effective in lowering blood pressure in resistant hypertension. In this review, we summarize and critically discuss the evidence for new drugs mitigating aldosterone in heart failure, hypertension, and chronic kidney disease.

8Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.PubMed

Suetonia C Palmer, Britta Tendal, Reem A Mustafa, et al.
OBJECTIVE: To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. DESIGN: Network meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. MAIN OUTCOME MEASURES: Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. RESULTS: 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 3 to 40 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. CONCLUSIONS: In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with some differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019153180.

9Combination therapy: an upcoming paradigm to improve kidney and cardiovascular outcomes in chronic kidney disease.PubMed

Radica Z Alicic, Joshua J Neumiller, Katherine R Tuttle
UNLABELLED: In this article the authors review recent advances in the treatment of chronic kidney disease (CKD) with diabetes, and summarize evidence supporting combination therapy approaches to improve patient outcomes. Driven by the global rise in diabetes, the worldwide burden of CKD has nearly doubled since the 1990s. People with CKD have notably increased risks for premature cardiovascular disease (heart and blood vessels disease), kidney failure and death. CKD, diabetes, obesity and cardiovascular disease are closely interrelated and share common risk factors. These health conditions therefore comprise what is now known as cardiovascular-kidney-metabolic (CKM) syndrome. Recently approved medications, including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the non-steroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone, represent agents capable of reducing metabolic, kidney and cardiovascular risk through complementary mechanisms of action. Current evidence supports use of these therapies in combination. Besides providing additive protective effects, combination therapy may also help reduce side effects. For instance, using an SGLT2 inhibitor in combination with finerenone helps decrease the risk for high potassium levels. Through the multipronged approach, combination therapy allows tailoring treatment for the individual patient characteristics and needs. Several planned and ongoing clinical trials continue to study the benefits of combination therapy in people with CKM syndrome. With building evidence supporting the use of combination therapy, it is crucial to raise awareness of the importance of this treatment approach and develop processes to incorporate new therapies into every day practice to support optimal care and improved outcomes. ABSTRACT: The global burden of chronic kidney disease (CKD) increased by nearly 90% in the period spanning 1990 to 2016, mostly attributed to an increase in the prevalence of CKD in diabetes. People living with CKD have an elevated lifetime risk for cardiovascular disease (CVD) when compared with the general population, with risk increasing in parallel with albuminuria and kidney function decline. Metabolic disease, CKD and CVD share common risk factors including neurohumoral activation, systemic inflammation and oxidative stress, thus prompting the introduction of a broader construct of cardiovascular-kidney-metabolic (CKM) syndrome. An important rationale for the introduction of this concept are recent and ongoing therapeutic advancements fundamentally changing CKM management. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the non-steroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone have shifted the therapeutic paradigm for patients with CKD and have emerged in rapid succession as cornerstones of guideline-directed medical therapy (GDMT). Recently completed clinical trials of aldosterone synthase inhibitors and endothelin receptor antagonists have additionally reported additive antiproteinuric effects on the background of renin-angiotensin system and SGLT2 inhibition, with acceptable safety profiles. The sum of current evidence from both preclinical and clinical studies support combination therapy in the setting of CKD to achieve additive and potentially synergistic kidney and heart protection by addressing metabolic, hemodynamic, and pro-inflammatory and pro-fibrotic mechanistic pathways. This narrative review will discuss available evidence supporting combination GDMT in CKD with diabetes and additionally discuss ongoing and future trials evaluating the efficacy and safety of combination therapies for CKD with or without diabetes.

10Executive summary of the KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease: an update based on rapidly emerging new evidence.PubMed

Peter Rossing, M Luiza Caramori, Juliana C N Chan, et al.
The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (CKD) represents a focused update of the KDIGO 2020 guideline on the topic. The guideline targets a broad audience of clinicians treating people with diabetes and CKD. Topic areas for which recommendations are updated based on new evidence include Chapter 1: Comprehensive care in patients with diabetes and CKD and Chapter 4: Glucose-lowering therapies in patients with type 2 diabetes (T2D) and CKD. The content of previous chapters on Glycemic monitoring and targets in patients with diabetes and CKD (Chapter 2), Lifestyle interventions in patients with diabetes and CKD (Chapter 3), and Approaches to management of patients with diabetes and CKD (Chapter 5) has been deemed current and was not changed. This guideline update was developed according to an explicit process of evidence review and appraisal. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence, and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, and areas for which additional research is needed are presented.

11Type 2 diabetes pharmacotherapy trends in high-risk subgroups.PubMed

Jay Bae, Dongju Liu, Chanadda Chinthammit, et al.
Medication use trends among patients with type 2 diabetes from 2015 to 2019 were investigated in relation to the clinical group-specific recommendations from the 2018 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus report. Data were drawn from a large health insurance claims database representing Commercial (total patient-year count: 2,379,704) and Medicare (total patient-year count: 845,823) insurance programmes (IBM® MarketScan®). The utilization of sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists increased over time but was lower in the Medicare cohort in every year evaluated. Patients diagnosed with obesity received recommended therapies at higher rates than those without obesity. Differences were more modest between those with versus without atherosclerotic cardiovascular disease (ASCVD) or chronic kidney disease, with greater treatment adoption in those without ASCVD in the Medicare cohort. Utilization of recommended treatments was paradoxically lower in those with versus without heart failure, and worse in the Medicare than in the Commercial cohort. Utilization of sulphonylureas was not different in those with versus without severe hypoglycaemia history. In conclusion, utilization of therapies recommended in the guidelines is increasing overall, which is not preferentially guided by ADA/EASD-defined clinical groups, and there exists a persistent gap in utilization between Commercial and Medicare populations.

12Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis.PubMed

Kailei Nong, Britta Tendal Jeppesen, Qingyang Shi, et al.
OBJECTIVE: To provide up-to-date evidence on key benefits, harms, and uncertainties regarding medications for adults with type 2 diabetes. DESIGN: Living systematic review and network meta-analysis (NMA), using frequentist random effects and GRADE (grading of recommendations, assessment, development and evaluation) approaches. Updates are planned at least two times a year. DATA SOURCES: Medline and Embase, searched up to 31 July 2024 for the current iteration. STUDY SELECTION: Randomised controlled trials of at least 24 weeks comparing one or more medications with standard treatment, placebo, or each other. RESULTS: The systematic review and NMA includes 493 168 participants from 869 trials (adding 53 trials since October 2022) reporting data for 13 drug classes (63 drugs) and 26 outcomes of interest. Regarding benefits, moderate to high certainty evidence confirms the well established cardiovascular and kidney benefits of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and finerenone (the last for patients with established chronic kidney disease). The most effective drugs in reducing body weight were tirzepatide (mean difference (MD) -8.63 kg (95% confidence interval -9.34 to -7.93); moderate certainty) and orforglipron (MD -7.87 kg (-10.24 to -5.50); low certainty), followed by eight other GLP-1RAs (high to moderate certainty). Absolute benefits of medications vary substantially depending on the baseline risk of cardiovascular and kidney outcomes; risk-stratified absolute effects of medications are summarised using an interactive multiple comparisons tool (https://matchit.magicevidence.org/250709dist-diabetes/#!/). Regarding medication-specific harms, SGLT-2 inhibitors increase genital infections (odds ratio (OR) 3.29 (95% CI 2.88 to 3.77); high certainty) and ketoacidosis due to diabetes (OR 2.08 (1.45 to 2.99); high certainty), and probably increase amputations (OR 1.27 (1.01 to 1.61); moderate certainty); tirzepatide and GLP-1RAs probably increase severe gastrointestinal events (most increased risk with tirzepatide (OR 4.21 (1.87 to 9.49); moderate certainty)); finerenone increases severe hyperkalaemia (OR 5.92 (3.02 to 11.62); high certainty); and thiazolidinediones increase major osteoporotic fractures and probably increase hospitalisation for heart failure. Sulfonylureas, insulin, and dipeptidyl peptidase-4 inhibitors probably increase the risk of severe hypoglycaemia. There is low to very low certainty evidence for effects on other diabetes-related complications, including neuropathy and visual impairment. Despite interest in the issue, there is uncertainty about whether GLP-1RAs may reduce dementia (OR 0.92 (0.83 to 1.02); low certainty). CONCLUSIONS: This living systematic review provides a comprehensive summary of the cardiovascular, kidney, and weight loss benefits, as well as medication-specific harms of medications for adults with type 2 diabetes, including effects of SGLT-2 inhibitors, GLP-1RAs, finerenone and tirzepatide. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number: CRD42022325948. A more detailed protocol is available at https://data.aliveevidence.org/records/q02rv-km486. READERS' NOTES: This article is the first version of a living systematic review. It is linked to a living Rapid Recommendation and other living clinical practice guidelines, presenting risk stratified recommendations for patients with type 2 diabetes at lower, moderate, and higher risk of cardiovascular and kidney complications. The latest evidence will be made available via the Rapid Recommendation and via an interactive GRADE evidence summary (MATCH-IT: https://matchit.magicevidence.org/250709dist-diabetes/#!/). Major updates will be published in .

13[New guideline on diabetes management in chronic kidney disease].PubMed

Christoph Wanner, Martin Busch
In autumn 2022, an update of the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on diabetes management in chronic kidney disease (CKD) was published. This article presents in a clear manner and discusses the new aspects compared to the 2020 guideline. Innovations are seen in the area of general and all-encompassing treatment as well as in relation to blood glucose-lowering and organ-protective treatments with sodium-glucose cotransporter 2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide‑1 receptor agonists. A new feature is also the top 10 recommendations on diabetes management in CKD for both patients and physicians. The KDIGO guideline on diabetes management in CKD represents the current evidence-based standard of care for patients with diabetes mellitus and CKD. It is now important to implement the guideline in order to provide patients with the benefits of the treatments and thus improve their lives.

14Guideline recommendations and the positioning of newer drugs in type 2 diabetes care.PubMed

Nikolaus Marx, Melanie J Davies, Peter J Grant, et al.
Cardiovascular outcome trials in patients with type 2 diabetes at high cardiovascular risk have led to remarkable advances in our understanding of the effectiveness of GLP-1 receptor agonists and SGLT2 inhibitors to reduce cardiorenal events. In 2019, the American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), and European Society of Cardiology (ESC) published updated recommendations for the management of such patients. We are concerned that ongoing discussions focusing on the differences between the endocrinologists' consensus report from the ADA and EASD and cardiologists' guidelines from the ESC are contributing to clinical inertia, thereby effectively denying evidence-based treatments advocated by both groups to patients with type 2 diabetes and cardiorenal disease. A subset of members from the writing groups of the ADA-EASD consensus report and the ESC guidelines was convened to emphasise where commonalities exist and to propose an integrated framework that encompasses the views incorporated in management approaches proposed by the ESC and the ADA and EASD. Coordinated action is required to ensure that people with type 2 diabetes, cardiovascular disease, heart failure, or chronic kidney disease are treated appropriately with an SGLT2 inhibitor or GLP-1 receptor agonist. In our opinion, this course should be initiated independent of background therapy, current glycaemic control, or individualised treatment goals.

15Cardiovascular, kidney related, and weight loss effects of therapeutics for type 2 diabetes: a living clinical practice guideline.PubMed

Arnav Agarwal, Reem Mustafa, Veena Manja, et al.
CLINICAL QUESTION: What are the benefits and harms of medications for adults with type 2 diabetes at varied risks of cardiovascular and kidney related complications? CONTEXT: Emerging clinical trials of novel medications have demonstrated benefits on cardiovascular, kidney, and weight related outcomes in people with type 2 diabetes. Dynamically updated practice guidelines adhering to standards of trustworthiness are necessary in response to a rapidly evolving evidence base and the availability of multiple medication alternatives. This living practice guideline incorporates the latest available medications and evidence and provides recommendations stratified by risks of cardiovascular and kidney complications to inform diabetes management. RECOMMENDATIONS: The panel issued risk-stratified recommendations regarding four prioritised medications for adults with type 2 diabetes (SGLT-2 inhibitors, GLP-1 receptor agonists, finerenone and tirzepatide):• Lower risk (three or fewer cardiovascular risk factors without established cardiovascular disease (CVD) or chronic kidney disease (CKD)): weak recommendation against SGLT-2 inhibitors or GLP-1 receptor agonists.• Moderate risk (more than three cardiovascular risk factors without established CVD or CKD; or established CVD and/or CKD at lower risk of complications): weak recommendation in favour of SGLT-2 inhibitors or GLP-1 receptor agonists; and a weak recommendation against finerenone in adults with CKD.• Higher risk (established CVD and/or CKD at higher risk of complications, or established heart failure): strong recommendation in favour of SGLT-2 inhibitors or GLP-1 receptor agonists; and a weak recommendation in favour of finerenone in adults with CKD.• Across risk strata: weak recommendation in favour of tirzepatide in adults with obesity. ABOUT THIS GUIDELINE AND HOW IT WAS CREATED: An international panel including two patient partners, clinicians, and methodologists produced these recommendations. The panel followed standards for trustworthy guidelines and used the GRADE approach, explicitly considering the balance of benefits, harms and burdens of treatment from an individual patient perspective. Recommendations were informed by a linked living systematic review and network meta-analysis evaluating relative benefits and harms updated to 31 July 2024; and by linked systematic reviews addressing risk prediction models and values and preferences of adults with type 2 diabetes. Candidate therapeutics are prioritised based on availability of sufficient randomised trial data, relevance to a global audience and likelihood of changing practice.This is the first version of the living guideline. The guideline is part of the series. MAGICapp displays the most recent version of the guideline and full content including evidence summaries and decision aids; major updates will be published in . We encourage re-use, adaptation and translation of these living guidelines, and recognise that the lack of availability or high costs of some medications may be prohibitive and will impact on how these recommendations are implemented across different health care systems.

16Factors Affecting Prescribing of Type 2 Diabetes Medications in Older Adults within an Integrated Healthcare System.PubMed

Mia E Lussier, Michael R Gionfriddo, Jove H Graham, et al.
BACKGROUND: Despite type 2 diabetes guidelines recommending against the use of sulfonylureas in older adults and for the use of sodium-glucose cotransporter-2 inhibitors (SGLT2) and glucagon-like peptide-1 agonists (GLP1s) in patients with atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and heart failure (HF), real-world guideline-concordant prescribing remains low. While some factors such as cost have been suggested, an in-depth analysis of the factors associated with guideline-concordant prescribing is warranted. OBJECTIVE: To quantify the extent of guideline-concordant prescribing in an integrated health care delivery system and examine provider and patient level factors that influence guideline-concordant prescribing. DESIGN: We performed a cross-sectional study. PARTICIPANTS: Participants were included if they had a diagnosis of type 2 diabetes, were prescribed a second-line diabetes medication between January 1, 2018 and December 31, 2020 and were at least 65 years old at the time of this second-line prescription. MAIN MEASURES: Our outcome of interest was guideline-concordant prescribing. The definition of guideline-concordant prescribing was based on American Diabetes Association and American Geriatric Society recommendations as well as expert consensus. Factors affecting guideline concordant prescribing included patient demographics and provider characteristics among others. KEY RESULTS: We included 1,693 patients of which only 50% were prescribed guideline-concordant medications. In a subgroup of 843 patients with cardiorenal conditions, only 30% of prescriptions were guideline concordant. Prescribing of guideline-concordant prescriptions was more likely among pharmacists than physicians (RR 1.34, 95% CI 1.19-1.51, p<0.001) and in endocrinology practices compared to primary care practices (RR 1.41 95% CI 1.16-1.72, p=0.007). Additionally, guideline concordant prescribing increased over time (42% in 2018 vs 53% in 2019 vs 53% in 2020, p<0.001). CONCLUSIONS: Guideline-concordant prescribing remains low in older adults, especially among those with cardiorenal conditions. Future studies should examine barriers to prescribing guideline-concordant medications and interventions to improve guideline-concordant prescribing.

17New Perspectives in Management of Cardiovascular Risk Among People With Diabetes.PubMed

Abhishek Gami, Roger S Blumenthal, Darren K McGuire, et al.
Following the publication of results from multiple landmark cardiovascular outcome trials of antihyperglycemic medications over the past 8 years, there has been a major shift in the focus of care for people with type 2 diabetes, from control of hyperglycemia to managing cardiovascular risk. Multiple international cardiology and diabetes society guidelines and recommendations now endorse sodium-glucose cotransporter-2 inhibitors and glucagon-like protein-1 receptor agonists as first-line therapies to mitigate cardiovascular risk. The most recent publication is the 2023 European Society of Cardiology guideline on the management of cardiovascular disease in those with type 2 diabetes that, for the first time, recommends use of both classes of medications for the mitigation of cardiovascular risk for those with or at high risk for atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease. Here, we review the evidence behind contemporary society guidelines and recommendations for the management of type 2 diabetes and cardiovascular risk.

18Sodium-glucose cotransporter-2 (SGLT-2) inhibitors for adults with chronic kidney disease: a clinical practice guideline.PubMed

Arnav Agarwal, Xiaoxi Zeng, Sheyu Li, et al.
CLINICAL QUESTION: What is the impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on survival and on cardiovascular and kidneyoutcomes for adults living with chronic kidney disease (CKD)? CURRENT PRACTICE: Few therapies slow kidney disease progression and improve long term prognosis for adults living with CKD. SGLT-2 inhibitors have demonstrated cardiovascular and kidney benefits in adults with CKD with and without type 2 diabetes. Existing guidance for SGLT-2 inhibitors does not account for the totality of current best evidence for adults with CKD and does not provide fully stratified treatment effects and recommendations across all risk groups based on risk of CKD progression and complications. RECOMMENDATIONS: The guideline panel considered evidence regarding benefits and harms of SGLT-2 inhibitor therapy for adults with CKD over a five year period, along with contextual factors, and provided the following recommendations:1. For adults at low risk of CKD progression and complications, we suggest administering SGLT-2 inhibitors (weak recommendation in favour)2. For adults at moderate risk of CKD progression and complications, we suggest administering SGLT-2 inhibitors (weak recommendation in favour)3. For adults at high risk of CKD progression and complications, we recommend administering SGLT-2 inhibitors (strong recommendation in favour)4. For adults at very high risk of CKD progression and complications, we recommend administering SGLT-2 inhibitors (strong recommendation in favour).Recommendations are applicable to all adults with CKD, irrespective of type 2 diabetes status. HOW THIS GUIDELINE WAS CREATED: An international panel including patients, clinicians, and methodologists produced these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel identified typical risk strata of adults with CKD (from low to very high risk of CKD progression and related complications) using the classification system developed by Kidney Disease Improving Global Outcomes (KDIGO), and applied an individual patient perspective in moving from evidence to recommendations. Effects of SGLT-2 inhibitors were interpreted in absolute terms applicable to different risk strata with varying baseline risks for outcomes of benefit over a five year period. The panel explicitly considered the balance of benefits, harms, and burdens of starting an SGLT-2 inhibitor, incorporating the values and preferences of adults with different risk profiles. Interactive evidence summaries and decision aids accompany multilayered recommendations, developed in an online authoring and publication platform (www.magicapp.org) that allows reuse and adaptation. THE EVIDENCE: A linked systematic review and pairwise meta-analysis (13 trials including 29 614 participants) of benefits and harms associated with SGLT-2 inhibitors in adults with CKD with or without type 2 diabetes informed guidance. Among individuals at very high risk of CKD progression and complications, moderate to high certainty evidence shows SGLT-2 inhibitors (relative to placebo or standard care without SGLT-2 inhibitors) decrease all-cause and cardiovascular mortality, hospitalisation for heart failure, kidney failure, non-fatal myocardial infarction, and non-fatal stroke. Among individuals at high risk, moderate to high certainty evidence shows SGLT-2 inhibitors result in similar benefits across outcomes except demonstrating little or no effect on hospitalisation for heart failure and kidney failure. Among individuals at moderate and low risk, moderate to high certainty evidence shows SGLT-2 inhibitors probably reduce all-cause mortality and non-fatal stroke, with little or no effect for other outcomes of benefit. Risk-stratified estimates were unavailable for outcomes of harm; the panel therefore considered absolute effects summarised across risk strata. SGLT-2 inhibitors are associated with little or no effect on acute kidney injury requiring dialysis, bone fractures, lower limb amputations, ketoacidosis, genital infections, or symptomatic hypovolaemia, although a residual possibility of harms at the individual patient level remains. UNDERSTANDING THE RECOMMENDATION: In order to apply recommendations, clinicians must appropriately identify adults with CKD, consider the underlying aetiology, and risk stratify them based on glomerular filtration rate (estimated or measured) and degree of albuminuria. In addition to classifying individuals into risk strata, further estimation of a given patient's risk based on the extent of their kidney disease and other comorbidities may be warranted to inform individual-level decisions and shared decision making. Available risk calculators may help estimate a given patient's risk of CKD progression and complications.

19Kidney Disease and Heart Failure: Recent Advances and Current Challenges: Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.PubMed

Carolyn S P Lam, Biykem Bozkurt, David Z I Cherney, et al.
Heart failure (HF) and chronic kidney disease (CKD) frequently coexist, which elevates the risks of hospitalization, disease progression, and death. Despite advances in treating each condition independently, many challenges remain in diagnosing and managing them in combination. In March 2024, Kidney Disease: Improving Global Outcomes (KDIGO) held the Controversies Conference on Kidney Disease and Heart Failure: Recent Advances and Current Challenges. Discussions highlighted the complex, bidirectional relationship between HF and CKD, including shared risk factors and overlapping pathophysiology as well as nuances in interpreting biomarkers such as natriuretic peptides and serum creatinine. Sodium-glucose cotransporter-2 inhibitors, renin-angiotensin-aldosterone system inhibitors, and emerging agents such as finerenone and glucagon-like peptide-1 receptor agonists can have benefits in both populations of patients with HF and CKD, though evidence in advanced CKD remains limited. Importantly, small declines in kidney function after initiating guideline-directed HF therapies generally do not require discontinuation, as these declines are often hemodynamic in nature and not associated with poor outcomes. The group highlighted the need for CKD-specific HF diagnostic thresholds and refined acute kidney injury definitions in HF. It is important for future cardiovascular and kidney trials to include relevant end points, such as kidney function trajectories, symptom burden, and quality of life. To improve care for individuals with HF and CKD, a more integrated approach to management, rooted in individualization, clinical context, and shared therapeutic goals, is needed.

20The interplay between heart failure and chronic kidney disease.PubMed

Anuradha Lala, Adeera Levin, Kamlesh Khunti
Chronic kidney disease (CKD) and heart failure (HF) are two globally prevalent, independent, long-term conditions, which often coexist in an individual and display a bidirectional yet interconnected relationship. The presence of CKD often leads to the development of HF and vice versa, which propagates the worsening of each disease, reflecting an intertwined disease cycle. Both HF and CKD share common risk factors, such as increasing age, diabetes, high blood pressure, obesity and smoking. Data show that approximately half of all people with HF also have CKD, which impacts patient burden and quality of life due to a significantly greater risk of hospitalization and death, compared with those that have either CKD or HF. To maximize treatment effectiveness in individuals with both HF and CKD, healthcare professionals should recognize that these two diseases are systemic conditions, representing organ-specific manifestations of similar underlying processes. It is also essential to understand the role of renin-angiotensin system inhibitors, sodium-glucose cotransporter 2 inhibitors, the nonsteroidal mineralocorticoid receptor antagonist finerenone, and glucagon-like peptide-1 receptor agonists in managing these conditions. Lifestyle modifications should also be recommended. This review discusses factors contributing to the interplay between HF and CKD and the key role of healthcare professionals in providing appropriate treatment for the co-existing diseases.
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