Effectiveness in clinical practice versus efficacy of dipeptidyl peptidase-4 inhibitors in clinical trials for type 2 diabetes: protocol for systematic review

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Systematic review and meta-analysis

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (A10BH) Dipeptidyl peptidase 4 (DPP-4) inhibitors

  Dipeptidyl peptidase 4 (DPP-4) inhibitors
• Medical condition to be studied:
  Type 2 diabetes mellitus

Population studied

• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Renal impaired

  Hepatic impaired

  Immunocompromised

  Pregnant women
• Estimated number of subjects:
  0

Study design details

• Main study objective:
  To compare the results obtained for efficacy and effectiveness endpoints on clinical trials and those obtained from routine clinical practice of DPP4 inhibitors.
• Outcomes:
  Efficacy endpoints: mean change from baseline 1) in haemoglobin A1C (HbA1c), 2) in fasting plasma glucose, 3) glucose, 4) in body weight, and number of patients achieving HbA1c<7%. Effectiveness endpoints: all-cause mortality, cardiovascular-related mortality, acute myocardial infarction, stroke, hospitalisations, emergency department visits, amputations, nephropathy and retinopathy.
• Data analysis plan:
  The methodological quality of the RCT and observational studies will be assessed using Downs and Black checklist, while the AMSTAR 2 instrument will be used for the meta-analysis.To compare efficacy results of the DPP4 inhibitors when used in clinical trials context with their effectiveness in routine clinical practice,meta-analyses will be carried out for premarketing and postmarketing data.For continuous outcomes, the weighted mean differences between the intervention group and the comparator group, with their 95%CI,will be estimated using a random effects model.If a study does not report the SD, this will be calculated from the sample size and the SE or the 95%CI.The risk ratios and the 95%CI will be estimated for dichotomous outcomes, also using a random effects model.Between studies, heterogeneity will be assessed using the I2 statistic.The publication bias will be examined through visual inspection of a funnel plot and statistically evaluated by Egger's regression asymmetry test.