EFFICACY AND SAFETY OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS- SYSTEMATIC REVIEW AND META-ANALYSIS
Author(s)
Pérez A1, Franch J2, Fuster E3, Paz S4, Prades M4, Granell M3
1Hospital de la Santa Creu I Sant Pau, Barcelona, Spain, 2EAP Raval Sud- Institut Català de la Salut - USR Barcelona ciutat - IDIAP Jordi Gol, Barcelona, Spain, 3Novartis Farmaceutica, Barcelona, Spain, 4Outcomes'10, Castellon, Spain
OBJECTIVES To determine the efficacy and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes patients according to published data METHODS A systematic review of randomized clinical trials (RCT) in MEDLINE, Cochrane, ISI WOK, SCOPUS and clinicaltrials.gov databases was performed. Eligible studies were RCT with a treatment duration of at least 24 weeks evaluating efficacy (HbA1c, fasting plasma glucose-FPG- and weight variation from baseline) and/or safety (hypoglycemia rate) of DPP4 inhibitors (linagliptin, saxagliptin, sitagliptin, vildagliptin) compared with placebo or non-insulin monotherapy or combination, published in English or Spanish until June 2013. A meta-analysis was conducted using a random effects model. Standardized mean difference (SMD) for efficacy variables and relative risk (RR) for safety variable with 95% confidence intervals (CI) were calculated. RESULTS Of the 4,582 publications retrieved, 3,807 were deleted by duplicate review, 581 by title/abstract review and 139 by criteria compliance. Finally, 55 RCT were selected. DPP-4 inhibitor monotherapy was associated to greater reductions in HbA1c and FPG compared with placebo [SMD=-0.60, 95% CI=-0.75; -0.46 and SMD=-0.51, 95% CI=-0.62; -0.39, respectively] while compared with metformin the reductions were lower [SMD=0.28, 95% CI=0.20; 0.26 and SMD=0.36, 95% CI=0.27; 0.44, respectively]. DPP-4 inhibitors added to metformin lowered HbA1c and FPG significantly more than metformin monotherapy [SMD=-0.52, 95% CI=-0.62;-0.41 and SMD=-0.41, 95% CI=-0.51; -0.30, respectively], and achieved a greater decrease in weight and hypoglycemia risk versus sulfonylurea plus metformin [SMD=-0.55, 95% CI=-0.64; -0.45 y RR=0.16, 95% CI=0.11; 0.21, respectively]. Moreover, the addition of DPP-4 inhibitors to sulfonylurea showed a greater reduction in HbA1c compared with sulfonylurea monotherapy [SMD=-0.54, 95% CI=-0.70; -0.37]. CONCLUSIONS DPP-4 inhibitors added to metformin achieved a better glycemic control compared with metformin monotherapy, with a lower risk of hypoglycemia and without affecting weight versus sulfonilurea and metformin combination.
Conference/Value in Health Info
2014-11, ISPOR Europe 2014, Amsterdam, The Netherlands
Value in Health, Vol. 17, No. 7 (November 2014)
Code
PDB23
Topic
Clinical Outcomes, Epidemiology & Public Health
Topic Subcategory
Comparative Effectiveness or Efficacy, Safety & Pharmacoepidemiology
Disease
Diabetes/Endocrine/Metabolic Disorders