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After 4 years of oral semaglutide plus basal insulin therapy (based on data published by Khunti et al , which indicated patients receiving basal insulin are treated for a median of 3.7 years before intensifying treatment), patients were assumed to discontinue oral semaglutide and SGLT-2 inhibitor therapy and intensify to basal-bolus insulin (alongside concomitant metformin), which they received for the remainder of their lifetimes.37 BMI was modelled to remain constant following application of treatment effects in the first year of the analysis, revert to baseline on initiation of basal insulin, and increase on initiation of bolus insulin based on the insulin-experienced multivariate prediction equations published by Willis et al (online supplemental figure S2).38 Other physiological parameters, including blood pressure and serum lipids, were modelled to follow the progression equations built into the IQVIA Core Diabetes Model, based on the UKPDS and Framingham data, respectively (as described by Palmer et al ).30 Supplemental material In the 2-year delay arm, patients continued to receive metformin plus an SGLT-2 inhibitor for the first 2 years of the analysis, with HbA1c following the UKPDS 68 progression equation, before intensifying with the addition of oral semaglutide

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NEFA, non-esterified fatty acids

Methotrexate ameliorates systemic inflammation and septic associated-lung damage in a cecal ligation and puncture septic rat model

This deceleration reflects normal adaptation rather than protocol failure