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  • Review Article
  • Published:

Emerging treatments for post-transplantation diabetes mellitus

Nature Reviews Nephrology volume 11, pages 465–477 (2015)Cite this article

Subjects

Key Points

  • Post-transplantation diabetes mellitus (PTDM) is a frequent complication among renal transplant recipients and is associated with a reduced life expectancy

  • Pretransplantation risk factors for PTDM include family history of diabetes mellitus, increasing age, obesity, a sedentary lifestyle, and impaired glucose tolerance before transplantation

  • Diagnosis of PTDM should be made on the basis of fasting glucose levels, supplemented with an oral glucose tolerance test if needed; the glycated haemoglobin test is not a well validated diagnostic tool

  • Drugs used to treat PTDM should not interact with immunosuppressive agents, elicit weight gain or hypoglycaemic events, or reduce glomerular filtration rate

  • Short-term use of the DPP-4 inhibitors sitagliptin and vildagliptin, as well as glinides have been shown to be safe and effective in small clinical trials

  • The use of GLP-1 analogues, SGLT2 inhibitors, and metformin at GFR <60 ml/min/1.73 m2 needs to be explored among patients with PTDM

Abstract

Post-transplantation diabetes mellitus (PTDM), also known as new-onset diabetes mellitus (NODM), occurs in 10–15% of renal transplant recipients and is associated with cardiovascular disease and reduced lifespan. In the majority of cases, PTDM is characterized by β-cell dysfunction, as well as reduced insulin sensitivity in liver, muscle and adipose tissue. Glucose-lowering therapy must be compatible with immunosuppressant agents, reduced glomerular filtration rate (GFR) and severe arteriosclerosis. Such therapy should not place the patient at risk by inducing hypoglycaemic episodes or exacerbating renal function owing to adverse gastrointestinal effects with hypovolaemia. First-generation and second-generation sulphonylureas are generally avoided, and caution is currently advocated for the use of metformin in patients with GFR <60 ml/min/1.73 m2. DPP-4 inhibitors do not interact with immunosuppressant drugs and have demonstrated safety in small clinical trials. Other therapeutic options include glinides and glitazones. Evidence-based treatment regimens used in patients with type 2 diabetes mellitus cannot be directly implemented in patients with PTDM. Studies investigating the latest drugs are required to direct the development of improved treatment strategies for patients with PTDM. This Review outlines the modern principles of glucose-lowering treatment in PTDM with specific reference to renal transplant recipients.

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Figure 1: First and second phase insulin release and corresponding glycaemia after an intravenous glucose challenge.
Figure 2: Target organs of current and candidate glucose-lowering drugs in post-transplantation diabetes mellitus.

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Authors and Affiliations

  1. Department of Clinical Medicine, Research Group of Nephrology and Metabolism, UIT Arctic University of Norway, Hansine Hansens Veg 18, PO Box 6050, Langnes, 9037, Tromsø, Norway

    Trond Jenssen

  2. Department of Transplant Medicine, Section of Nephrology, Oslo University Hospital Rikshospitalet, Sognsvannvegen 20, PO Box 4950, Nydalen, 0424, Oslo, Norway

    Anders Hartmann

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  1. Trond Jenssen
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T.J. wrote the article. Both authors researched the data for the article, provided substantial contributions to discussions of its content, and undertook review and/or editing of the manuscript before submission.

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Correspondence to Trond Jenssen.

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Competing interests

T.J. has received lecture honoraria from AstraZeneca, Novartis, Sanofi, and Merck Sharp & Dohme. A.H. declares no competing interests.

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Jenssen, T., Hartmann, A. Emerging treatments for post-transplantation diabetes mellitus. Nat Rev Nephrol 11, 465–477 (2015). https://doi.org/10.1038/nrneph.2015.59

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