title: The place of DPP-4 inhibitors in the treatment algorithm of diabetes type 2: a systematic review of cost-effectiveness studies.
abstract: OBJECTIVE
  To conduct a systematic review of cost-effectiveness, cost-utility, and cost-benefit studies of DPP-4 inhibitors for diabetes treatment versus other antidiabetics.
  
  
  METHODS
  Three investigators searched the CRD York, Tufts CEA Registry, and MEDLINE databases through 2015. We reviewed all potentially relevant titles and abstracts, and screened full-text articles, according to inclusion criteria. We established a quality score for each study based on a 35-item list.
  
  
  RESULTS
  A total of 295 studies were identified, of which 20 were included. The average quality score was 0.720 on a 0-1 scale. All studies were performed in high- and middle-income countries, using a 3rd-party payer perspective and randomized clinical trials to measure effectiveness. Sitagliptin, saxagliptin and vildagliptin had an ICER below 25,000 €/QALY, as second-line and as add-ons to metformin, in comparison to sulfonylureas. When compared with sitagliptin, liraglutide (GLP-1 receptor agonist) had an ICER of up to 22,724 €/QALY for the 1.2-mg dosage, and up to 32,869 €/QALY for the 1.8-mg dosage. Insulin glargine was dominant when compared with sitagliptin.
  
  
  CONCLUSIONS
  According to the WHO threshold applied to the country and year of each study, DPP-4 inhibitors were highly cost-effective as second-line, as add-ons to metformin, in comparison with sulfonylureas. More recent therapies (GLP-1 receptor agonists and insulin glargine) were highly cost-effective in comparison to DPP-4 inhibitors. These results were obtained, however, on the basis of a limited number of studies, relying on the same few clinical trials, and financed by manufacturers. Further independent research is needed to confirm these findings.
authors.affiliation: Unit of Epidemiology of the Faculty of Medicine of Lisbon, Edifício Egas Moniz, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028, Lisbon, Portugal. alexcalaca@hotmail.com.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Baptista
authors.affiliation: Centre for Health Evaluation and Research (CEFAR), National Association of Pharmacies Group, R. Marechal Saldanha, 1., 1249-069, Lisbon, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Teixeira
authors.affiliation: Centre for Health Evaluation and Research (CEFAR), National Association of Pharmacies Group, R. Marechal Saldanha, 1., 1249-069, Lisbon, Portugal.
authors.forename: Sónia
authors.initials: S
authors.lastname: Romano
authors.affiliation: Center for Evidence-Based Medicine (CEMBE) of the Faculty of Medicine at the University of Lisbon, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028, Lisbon, Portugal.
authors.forename: António Vaz
authors.initials: AV
authors.lastname: Carneiro
authors.affiliation: Escola Nacional de Saúde Pública and Centro de Investigação em Saúde Pública, Universidade Nova de Lisboa, Avenida Padre Cruz, 1600-5605, Lisbon, Portugal.
authors.forename: Julian
authors.initials: J
authors.lastname: Perelman
mesh_terms: D000465:Algorithms; D003362:Cost-Benefit Analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000191:economics / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000191:economics / Q000627:therapeutic use*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents
keywords: Cost-effectiveness studies; DPP-4 inhibitors; Diabetes; Systematic review