Treatment Intensification and Long-Term Disease Progression

Disease progression may be observed as a rise in HbA1c while on the same drug regimen, requiring intensification of therapy in order to regain glycaemic control [²⁸]. Patients were assumed to receive either empagliflozin or oral semaglutide, in addition to metformin, until Hba1c of 7.5% (58 mmol/mol) was exceeded; this is the threshold for treatment intensification, defined in the NICE guidelines [¹⁹]. As soon as this threshold was exceeded, patients were assumed to intensify treatment with insulin glargine in addition to empagliflozin or oral semaglutide plus metformin, which would be continued lifelong in line with the combined ADA/EASD recommendations that SGLT2 and GLP1 receptor agonists are to be administered irrespective of the HbA1c measure [¹⁷].

Following the first year of treatment (study duration was 52 weeks), HbA1c and blood pressure were modelled to follow the UKPDS 68 progression equation for the remainder of patient lifetimes. Mortality was calculated using the UKPDS 82 combined mortality approach. The effect on BMI was assumed to be maintained while the patient remained on empagliflozin or oral semaglutide.