Table 1 Domains

Domain 1:c Metformin use

A first-line treatment not including metformin or any other combination of treatment not including metformin (without having tried metformin before and without known eGFR < 60  ml/min)

“number of diabetic medication/s > 0”

AND “metformin use = 0”

AND “prior use of metformin = 0”

AND “history of eGFR < 60 = 0”

Domain 2: Treatment intensification

Lack of treatment intensification (add-on or switch to a different regimen) when HbA1c was above personalized target for two consecutive visits

“two consecutive visits with Hba1c > Hba1c-targets = 1 ”

AND “changes in treatments*=0”

(*defined as add-on or switch to a different regimen in that visit as compared to the previous one)

Domain 3: Second line treatments

Use of sulfonylureas or insulin as second-line treatments

“number of diabetic medication = 2”

AND [“sulfonylureas use = 1” OR “insulin use = 1”]

AND “prior history of DPP4i = 0”

AND “prior history of GLP1-RAs = 0”

AND “prior history of SGLT2i = 0”

Domain 4: Insulin use

Inappropriate use of Insulin (e.g., initiation before GLP1-RAs or with bolus regimen before basal)

[“insulin use = 1” AND “prior history of GLP1RA = 0” AND “Last Hba1c > 10% = 0”]

OR

[“insulin use = 1” AND “prior history of metformin = 0” AND “history of eGFR < 60 = 0”]

OR

[rapid-insulin use = 1” AND “history of basal-insulin = 0” AND “Last Hba1c > 10% = 0”]

Domain 5: Use of cardioprotective drugs

[evaluated only on visits after year 2014]

Lack of cardio-protective treatments in patients with previous cardiovascular events or revascularization

[“history of CVD = 1” AND “GLP1-RAs use = 0” AND “SGLT2i use = 0” AND “prior history of GLP1-RAs = 0”

AND “prior history of SGLT2i = 0”]

OR

[“history of CHF = 1” AND “SGLT2i use = 0” AND “prior history of SGLT2i = 0” AND “history of eGFR < 60 = 0”]

Domain 6: Use of weight beneficial-natural drugs

Use of weight-increasing drugs (SU or insulin) in obese subjects (BMI > 30 kg/m2) prior to weight-neutral or weight-decreasing drugs (metformin, GLP1-RAs, SGLT2i, DPP4i)

{“BMI > 30”

AND [(“insulin use = 1” AND “last_HbA1c > 10%=0”) OR “sulfonylureas /glinides use = 1” OR “TZD use = 1”]

AND “prior history of metformin = 0”}

OR

{“BMI > 30”

AND [(“insulin use = 1” AND “last_HbA1c > 10%=0”) OR “sulfonylureas /glinides use = 1” OR “TZD use = 1”]

AND [(“prior history of DPP4i = 0” AND “prior history of GLP1-RAs = 0”) OR “prior history of SGLT2i = 0”]}