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  • Review Article
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Cardiorenal diseases in type 2 diabetes mellitus: clinical trials and real-world practice

Nature Reviews Endocrinology volume 19, pages 151–163 (2023)Cite this article

Subjects

Abstract

Patients with type 2 diabetes mellitus (T2DM) can have multiple comorbidities and premature mortality due to atherosclerotic cardiovascular disease, hospitalization with heart failure and/or chronic kidney disease. Traditional drugs that lower glucose, such as metformin, or that treat high blood pressure and blood levels of lipids, such as renin–angiotensin-system inhibitors and statins, have organ-protective effects in patients with T2DM. Amongst patients with T2DM treated with these traditional drugs, randomized clinical trials have confirmed the additional cardiorenal benefits of sodium–glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP1RA) and nonsteroidal mineralocorticoid receptor antagonists. The cardiorenal benefits of SGLT2i extended to patients with heart failure and/or chronic kidney disease without T2DM, whereas incretin-based therapy (such as GLP1RA) reduced cardiovascular events in patients with obesity and T2DM. However, considerable care gaps exist owing to insufficient detection, therapeutic inertia and poor adherence to these life-saving medications. In this Review, we discuss the complex interconnections of cardiorenal–metabolic diseases and strategies to implement evidence-based practice. Furthermore, we consider the need to conduct clinical trials combined with registers in specific patient segments to evaluate existing and emerging therapies to address unmet needs in T2DM.

Key points

  • In patients with type 2 diabetes mellitus (T2DM), improved risk factor control and the use of renin–angiotensin system inhibitors and statins have reduced the incidence of cardiovascular-renal events and related deaths.

  • Despite these improvements, cardiovascular and/or renal events and related death in patients with T2DM remain higher than in patients without T2DM.

  • Among patients with newly diagnosed or short duration of T2DM, early intensive glycaemic control to achieve near-normal blood levels of glucose might offer potential legacy effects on cardiovascular outcomes.

  • Sodium–glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists are preferred to prevent cardiovascular and/or renal complications and related death among patients with T2DM at high cardiorenal risk.

  • Multi-stakeholder engagement is needed to combine research and practice to close treatment gaps in guideline-directed medical therapy among patients at high cardiorenal risk through care re-organization with ongoing benchmarking.

  • Future research should address data gaps in risk stratification for cardiorenal complications, while clinical trials are required in women and patients with T2DM who are young or at low cardiorenal risk to address unmet needs.

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Fig. 1: Interlinked pathways to cardiorenal diseases in patients with T2DM.
Fig. 2: Combining research and practice to create a learning health-care system in T2DM management.

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Authors and Affiliations

  1. Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

    Lee-Ling Lim

  2. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China

    Lee-Ling Lim, Elaine Chow & Juliana C. N. Chan

  3. Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China

    Elaine Chow & Juliana C. N. Chan

  4. Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China

    Elaine Chow & Juliana C. N. Chan

  5. Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China

    Elaine Chow

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Contributions

L.L.L. and E.C. researched data for the article, wrote the article, contributed substantially to the discussion of content, and reviewed and/or edited the manuscript before submission. J.C.N.C. contributed substantially to the discussion of content and reviewed and/or edited the manuscript before submission.

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Correspondence to Juliana C. N. Chan.

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Competing interests

L.L.L. reported receiving research grants through her affiliated institutions, honoraria for consultancy and speaker fees from Abbott, AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novo Nordisk, Roche, Sanofi, Servier and Zuellig Pharma. E.C. has received speaker fees and/or institutional research support from Hua Medicine, Medtronic, Novartis and Sanofi. J.C.N.C. reported receiving research grants through her affiliated institutions, honoraria and speaker fees from Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Celltrion, Hua Medicine, Lee Powder, Lilly, Merck Sharpe Dohme, Merck Serono, Pfizer, Sanofi, Servier and Viatris Pharmaceutical; she holds patents of genetic markers for predicting diabetes and its complications; she is a co-founder of a biotechnology start-up company, GemVCare, with partial support from the Hong Kong Government Innovation and Technology Commission to provide precision diabetes care, and is Chief Executive Officer of Asia Diabetes Foundation on a pro bono basis.

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Lim, LL., Chow, E. & Chan, J.C.N. Cardiorenal diseases in type 2 diabetes mellitus: clinical trials and real-world practice. Nat Rev Endocrinol 19, 151–163 (2023). https://doi.org/10.1038/s41574-022-00776-2

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