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Clin Ther. 2011 Nov;33(11):1609-29. doi: 10.1016/j.clinthera.2011.09.028. Epub 2011 Nov 8.

Tolerability of dipeptidyl peptidase-4 inhibitors: a review.

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  • 1Wake Forest School of Medicine, Winston-Salem, North Carolina.



Oral glucose-lowering agents are used to treat patients with type 2 diabetes mellitus (T2DM). Most patients require multiple agents to maintain glycemic targets. Dipeptidyl peptidase-4 (DPP-4) inhibitors are administered as monotherapy and in combination therapy for the treatment of T2DM.


The aim of this article was to provide a thorough review of published tolerability data on 5 DPP-4 inhibitors.


PubMed and Web of Science were searched for English-language clinical trials published from January 2000 to June 2001, using the following key words: dipeptidyl peptidase-4 inhibitor, vildagliptin, alogliptin, sitagliptin, saxagliptin, linagliptin, safety, tolerability, efficacy, effect, AE, and adverse effect. Studies were considered for inclusion if they were randomized, double-blind trials performed in patients ≥18 years of age with T2DM and with a hemoglobin A(1c) of ≥6.5%; included ≥1 arm that received monotherapy with DPP-4; and reported adverse events (AEs). Studies in patients with a history of type 1 or secondary forms of diabetes, significant diabetic complications or cardiovascular disease within the 6 months before the start of the study, hepatic disease or abnormalities, and/or renal abnormalities were excluded.


A total of 45 clinical trials, 5 pharmacokinetic studies, and 28 meta-analyses or reviews were included. The duration of studies ranged from 7 days to 104 weeks. The most commonly reported AEs were nasopharyngitis, upper respiratory infections, all-cause infections, headache, gastrointestinal symptoms, and musculoskeletal pain. Based on the findings from the studies, the DPP-4 inhibitors had minimal impact on weight and were not associated with an increased risk for hypoglycemia relative to placebo. Rates of nasopharyngitis were higher with the DDP-4 inhibitors than with placebo. Pancreatitis was reported at lower rates with the DPP-4 inhibitors compared with other oral antihyperglycemic agents. Cardiovascular events were limited, and postmarketing studies are ongoing.


The tolerability of DPP-4 inhibitors is supported by published clinical trials. The rates of weight gain, gastrointestinal AEs, and hypoglycemia were minimal with the DPP-4 inhibitors studied.

Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
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