3,705
Views
165
CrossRef citations to date
0
Altmetric
Review

Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials

, , &
Pages 57-64 | Accepted 01 Jul 2011, Published online: 23 Nov 2011
 

Abstract

Objective:

Dipeptidyl peptidase-4 inhibitors (DPP4i) have been recently associated with increased risk of pancreatitis and cancer. The aim of the present meta-analysis of randomized clinical trials is the assessment of the effect of DPP4i on the incidence of major cardiovascular events (MACE), cancer, and pancreatitis.

Research design and methods:

An extensive Medline and Embase search for ‘vildagliptin’, ‘sitagliptin’, ‘saxagliptin’, ‘alogliptin’, ‘linagliptin’, and ‘dutogliptin’ was performed, collecting all randomized clinical trials on humans up to March 1, 2011. The present meta-analysis was therefore performed including all randomized clinical trials with a duration of at least 24 weeks, enrolling patients with type 2 diabetes, comparing DPP4i with either placebo or active drugs. Completed but still unpublished trials were identified through a search of www.clinicaltrials.gov, Food and Drug Administration, and European Medicines Agency website.

Results:

Fifty-three trials enrolling 20,312 and 13,569 patients for DPP4i and comparators, respectively, were included, reporting 176 malignancies, 257 MACE, and 22 pancreatitis. DPP4i, compared with placebo or other treatment, were associated with a similar risk of cancer (MH-OR 1.020 [0.742–1.402]; p = 0.90) and pancreatitis (0.786 [0.357–1.734], p = 0.55), and with a reduced risk of MACE (MH-OR 0.689 [0.528–0.899], p = 0.006).

Conclusions:

The present meta-analysis seems to exclude any relevant short term effect of DPP4i on the incidence of cancer and suggest a possible protection from cardiovascular events. This result should be interpreted with caution, as those events were not the principal endpoint, the trial duration was short, and the characteristics of patients included could be different from routine clinical practice.

Transparency

Declaration of funding

This study was performed as part of the institutional activity of the authors, without any external funding.

Daniele Martellia

Declaration of financial/other relationships

M.M. has received speaking fees from Bristol Myers Squibb, Merck, and Takeda. I.D. has received fees from Novo Nordisk for participation on speakers bureaus. E.M. has received consultancy fees from Merck and Novartis, speaking fees from Astra Zeneca, Bristol Myers Squibb, Merck, and Novartis, and research grants from Merck, Novartis, and Takeda. D.M. has no financial/other relationships to disclose.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.