Clinical outcomes of novel antidiabetic medicines: Real-world evidence from Slovenian population-based study (CONAMS)

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Drug utilisation

  Effectiveness study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (A10A) INSULINS AND ANALOGUES

  INSULINS AND ANALOGUES

  (A10BA) Biguanides

  Biguanides

  (A10BB) Sulfonylureas

  Sulfonylureas

  (A10BD) Combinations of oral blood glucose lowering drugs

  Combinations of oral blood glucose lowering drugs

  (A10BH) Dipeptidyl peptidase 4 (DPP-4) inhibitors

  Dipeptidyl peptidase 4 (DPP-4) inhibitors

  (A10BJ) Glucagon-like peptide-1 (GLP-1) analogues

  Glucagon-like peptide-1 (GLP-1) analogues

  (A10BK) Sodium-glucose co-transporter 2 (SGLT2) inhibitors

  Sodium-glucose co-transporter 2 (SGLT2) inhibitors

  (A10BX) Other blood glucose lowering drugs, excl. insulins

  Other blood glucose lowering drugs, excl. insulins
• Medical condition to be studied:
  Type 2 diabetes mellitus

Population studied

• Short description of the study population:
  Patients with type 2 diabetes treated with SGLT-2 inhibitors compared to those treated with DPP-4 inhibitors.; The database population consisted of all patients who filled at least two prescriptions for any antidiabetic medicine within 1 year prior to 30 June 2014. To minimise inclusion of patients with type 1 diabetes, gestational diabetes, or early-onset type 2 diabetes, we limited patient selection to those aged 40 years or older. From this patient population, we selected new users of SGLT2i or DPP-4i between 30 June 2014 and 30 June 2018 (recruitment period). To limit the sample to new users of SGLT2i or DPP-4i, we excluded patients treated with SGLT2i, DPP-4i, or GLP-1RA at any time before the index date. The inclusion period started on 30 June 2014, the date when the first drug from the SGLT2i group became available on the Slovenian market.
• 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:
  Other
• Special population of interest, other:
  Type 2 diabetes mellitus patients
• Estimated number of subjects:
  10000

Study design details

• Main study objective:
  First retrospective cohort study: to evaluate the effect of SGLT2 inhibitors and GLP-1 analogues compared with DPP-4 inhibitors on cardiovascular morbidity and mortality in patients with type 2 diabetes. Second retrospective cohort study: to compare the risk of amputation in patients with type 2 diabetes who were treated with SGLT2 inhibitors to those treated with DPP-4 inhibitors.
• Outcomes:
  First retrospective cohort study: occurrence of major adverse cardiovascular events as a composite endpoint (hospitalisations with a main diagnosis of myocardial infarction or ischemic stroke or cardiovascular death), hospitalisations due to heart failure, cardiovascular death and all-cause death. Second retrospective cohort study: occurrence of lower extremity amputations.
• Data analysis plan:
  First retrospective cohort study: a Cox regression model will be used to evaluate the effects of the antidiabetic medicine group on the risk of each outcome. Other variables will also be included in the regression model, such as patient age, gender, concomitant medications, duration of type 2 diabetes, etc. The primary analysis will be based on the “intention-to-treat” population and the secondary analysis will be performed on the “on-treatment” population. Second retrospective cohort study: patients from the SGLT2 inhibitor group and the DPP-4 inhibitor group will be matched in a 1:1 ratio using propensity score matching. A Cox regression model will be used to estimate hazard ratios for amputations in new users of SGLT2 inhibitors compared to new users of DPP-4 inhibitors.

Documents

Study publications

Zerovnik, S., Kos, M. & Locatelli, I. Risk of lower extremity amputations in pa…

Zerovnik S, Kos M, Locatelli I. Cardiovascular morbidity and mortality in patie…