Meta-analysis: DPP-4 Inhibitors for Type 2 Diabetes

Karagiannis T, Paschos P, Paletas K, Matthews DR, Tsapas A. Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis.
BMJ. 2012 Mar 12;344:e1369. doi: 10.1136/bmj.e1369. 

Karagiannis and colleagues conducted a systematic review and meta-analysis of 27 studies to evaluate the efficacy of DPP-4 inhibitors for treatment of type 2 diabetes when compared with other antihyperglycemic therapies. The primary outcome was change in A1C from baseline. Secondary outcomes, including proportion of patients achieving A1C <7%, change in body weight, hypoglycemia, all-cause mortality, and serious adverse events, were also examined.  

Findings related to the primary outcome (change in A1C from baseline):  

Monotherapy: DPP-4 inhibitor vs metformin  

  • DPP-4 inhibitors were associated with a smaller decline in A1C (weighted mean difference 0.20, 95% confidence interval [CI] 0.08 to 0.32, 95% prediction interval −0.14 to 0.54; I2=60%)  

Combination therapy with metformin: DPP-4 inhibitor vs sulfonylurea  

  • DPP-4 inhibitors were less effective than sulfonylureas in A1C reduction (weighted mean difference 0.07, 95% CI, 0.03 to 0.11, 95% prediction interval 0.02 to 0.13; I2=0%)  

Combination therapy with metformin: DPP-4 inhibitor vs pioglitazone  

  • No difference was observed in change in A1C between DPP-4 inhibitors and pioglitazone (weighted mean difference 0.09, 95% CI, −0.07 to 0.24, 95% prediction interval −1.4 to 1.57, I2=40%)  

Combination therapy with metformin: DPP-4 inhibitor vs GLP-1 agonist  

  • DPP-4 inhibitors were inferior to GLP-1 agonists in reducing A1C (weighted mean difference 0.49, 95% CI, 0.31 to 0.67; I2=27%)  

The rate of serious adverse events was lower with DPP-4 inhibitor + metformin combination therapy vs pioglitazone + metformin combination therapy, and similar when DPP-4 inhibitors were compared with all other treatments. No differences were observed with DPP-4 inhibitors vs other antihyperglycemic therapies with regard to all-cause mortality.  

An increased risk for hypoglycemia was seen with sulfonylurea + metformin combination therapy vs DPP-4 inhibitor + metformin combination therapy; hypoglycemia incidence was minimal for DPP-4 inhibitors vs all other antihyperglycemic therapies. Incidence of diarrhea, nausea, and vomiting was more common in subjects receiving metformin monotherapy or combination therapy with metformin + GLP-1 agonists compared with those receiving DPP-4 inhibitors. There was no difference in the rate of nasopharyngitis, or upper respiratory or urinary tract infections in the DPP-4 inhibitor group compared with the other antihyperglycemic therapies.  


July 2012 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest. 

Related content: 

Read more about this study and additional cutting-edge diabetes data in the May 2012 issue of Clinical Insights® in Diabetes. Click here. 

Meta-analysis: DPP-4 Inhibitors for Treatment of Type 2 Diabetes—Design  

Meta-analysis: DPP-4 Inhibitors for Treatment of Type 2 Diabetes—Change in A1C from Baseline  

Meta-analysis: DPP-4 Inhibitors for Treatment of Type 2 Diabetes—Adverse Events and All-Cause Mortality 

Last Modified: 11/18/2013