DPP-4 inhibitors and lipids: systematic review and meta-analysis.
BACKGROUND
Lipid profile is an important determinant of cardiovascular risk in type 2 diabetic patients. Available glucose-lowering agents can affect lipid levels. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to reduce total cholesterol, but results are inconsistent across trials. The present metaanalysis was designed to assess the effect of DPP-4 inhibitors on blood lipids, verifying possible differences across compounds of this class.


METHODS
An extensive search of Medline and the Cochrane Library (any date up to December 31, 2010, restricted to randomized clinical trials, published in English) was performed for all trials containing, in any field, the words "sitagliptin," "vildagliptin," "saxagliptin," "alogliptin," "linagliptin," and/or "dutogliptin." Completed but unpublished trials were identified through a search of the ClinicalTrials.gov website, using the same keywords as above. Differences in the endpoint levels and absolute or percent variations of lipids were assessed. A metaregression was performed on the trials specified above to assess the effect of putative moderators on the effect of DPP-4 inhibitors on plasma lipids, considering all drugs together and each one separately.


RESULTS
Although the number of trials of appropriate size and duration was high (n=53), only a small fraction of those (n=17) reported data on endpoint total, high-density lipoprotein, and low-density lipoprotein cholesterol, and triglyceride. The difference-in-means for endpoint versus baseline total cholesterol in patients on DPP-4 inhibitors treatment was significantly higher in comparison with controls, meaning that treatment with DPP-4 inhibitors is associated with a significant reduction in total cholesterol (-0.18 [-0.29; -0.06] mmol/L (-7.0 [-11.2; -2.50] mg/dL); P=0.002).


CONCLUSIONS
This meta-analysis suggests a possible beneficial effect of DPP-4 inhibitors on cholesterol, which, although small, could contribute to the reduction of cardiovascular risk.
Section of Geriatric Cardiology and Medicine, Department of Cardiovascular Medicine, Careggi, Teaching Hospital, Florence, Italy. mmonami@libero.it
Matteo
M
Monami
Caterina
C
Lamanna
Carla Maria
CM
Desideri
Edoardo
E
Mannucci
D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003920:Diabetes Mellitus / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008075:Lipoproteins, HDL / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism
D054873:Dipeptidyl-Peptidase IV Inhibitors; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides