The patient cohort was assumed to receive a first-line treatment of empagliflozin or sitagliptin, plus metformin as background therapy. An HbA1c threshold of 8.5% (69 mmol/mol) was defined which triggered the patients to receive an escalation therapy. Patients were switched to basal insulin therapy, as assumed in other recent analyses.30 (link),31 (link) In particular, an escalation therapy of insulin glargine 42 units per day with metformin as background therapy was considered in the analysis. Both treatment effect and adverse event rates of insulin glargine were derived from published literature data32 (link) (Table 4). The United Kingdom Prospective Diabetes Study (UKPDS) 82 risk equation33 (link) was used to model HbA1c after the first year for the remainder of the analysis. Similarly, also the evolution of blood pressure and serum lipids were predicted by applying the progression factors available in the IQVIA CDM (UKPDS 82 and Framingham). Regarding body mass index (BMI), as long as patients stayed on empagliflozin or sitagliptin, the impact on BMI was maintained.

Treatment Effects and Adverse Event Rates Applied in the Analyses for Patients without Established CVD (Second-Line Treatment)

Insulin
Physiological parameters (applied in the first year of the analysis), mean
HbA1c (change from baseline)−1.7
BMI (change from baseline)0.818
Adverse event rates (applied while patients received treatment)
NSHE rate (per 100 patient-years)486
SHE1 rate (per 100 patient-years)1.76
SHE2 rate (per 100 patient-years)0.24

Abbreviations: BMI, body mass index; HbA1c, glycated hemoglobin; NSHE, non-severe hypoglycemia rate; SBP, systolic blood pressure; SHE1, Severe hypoglycemic event (not requiring medical assistance); SHE2, Severe hypoglycemic event (requiring medical assistance).