Using DPP-4 inhibitors to modulate beta cell function in type 1 diabetes and in the treatment of diabetic kidney disease

ABSTRACT

Introduction: DPP-4 inhibitors have pleomorphic effects that extend beyond the anti-hyperglycemic labeled use of the drug. DPP-4 inhibitors have demonstrated promising renal protective effects in T2DM and T1DM and protective effects against immune destruction of pancreatic beta-cells in T1DM.

Areas covered: The efficacy of DPP-4 inhibitors in the treatment of diabetic kidney disease and possible adjunct with insulin in the treatment of T1DM to preserve beta-cell function. Pertinent literature was identified through Medline, PubMed and ClinicalTrials.gov (1997-November 2018) using the search terms T1DM, sitagliptin, vildagliptin, linagliptin, beta-cell function, diabetic nephropathy. Only articles are written in the English language, and clinical trials evaluating human subjects were used.

Expert opinion: DPP-4 inhibitors can be used safely in patients with diabetic kidney disease and do not appear to exacerbate existing diabetic nephropathy. Linagliptin reduces albuminuria and protects renal endothelium from the deleterious effects of hyperglycemia. The effects of DPP-4 inhibitors on preserving beta-cell function in certain subtypes of T1DM [e.g. Latent Autoimmune Diabetes in Adult (LADA) and Slowly Progressive Type 1 Diabetes (SPIDDM)] are encouraging and show promise.

Trial registration: ClinicalTrials.gov identifier: NCT01792518.

KEYWORDS:

• Beta-cell function
• diabetic nephropathy
• dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors)
• end stage renal disease (ESRD)
• glucagon-like peptide-1 (GLP-1)
• human
• latent autoimmune diabetes in adult (LADA)
• membrane-bound DPP4 (CD-26)
• rats
• renal disease
• slowly progressive type 1 diabetes (SPIDDM)
• type 1 diabetes (T1DM)
• type 2 diabetes (T2DM)

Article Highlights

1. DPP-4 inhibitors reduce kidney fibrosis and protect against glomerular disease in animal models of Type 1 DM.

2. Urinary DPP-4 levels are a promising biomarker for the onset of diabetic nephrology.

3. DPP-4 inhibitors do not appear to increase the risk of acute kidney injury and can improve multiple indices of chronic diabetic nephrology in T2DM.

4. DPP-4 (CD-26) in-vitro have effects on the deleterious immune pathway leading to T1DM and reduced beta cell function.

DPP-4 inhibitors show promise in slowing the progression of Latent Autoimmue Diabetes (LADA) and slowly progressive Type 1 Diabetes (SPIDDM).

This box summarizes the key points contained in the article.

Acknowledgments

We would like to thank Ms. Samantha Harbeson for her expert editorial assistance.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.