This was a substudy of a randomised trial which has been reported previously [30, (link)31, (link)32, (link)33] (link). Briefly, the SEMPA trial (Effect of Empagliflozin and Semaglutide on Cardio-Renal Target Organ Damage in Patients with Type 2 Diabetes -A Randomized Trial; European Union Drug Regulating Authorities Clinical Trials Database [EudraCT] registration no. 2019-000781-38) was a 32 week investigator-initiated, randomised, partly open-label, partly double-blinded placebo-controlled trial, designed to assess the separate and combined effects of semaglutide and empagliflozin on the two co-primary endpoints of arterial stiffness and renal oxygenation [30, (link)32] (link).
The trial consisted of two parallel designs (Fig. 1): (1) a double-blind, placebo-controlled, randomised clinical trial to evaluate the effects of tablet empagliflozin 10 mg once daily (Jardiance; Boehringer Ingelheim International, Germany) vs matching placebo; and (2) a parallel-group intervention open-label trial of onceweekly subcutaneous injection of semaglutide 1 mg or highest tolerated dose (Ozempic; Novo Nordisk, Denmark) in combination with tablet empagliflozin or tablet placebo treatment (double-blinded tablet empagliflozin treatment). This resulted in four groups receiving either tablet placebo, empagliflozin, a combination of semaglutide and placebo (herein referred to as the 'semaglutide' group), or a combination of semaglutide and empagliflozin (herein referred to as the 'combination-therapy' group). The semaglutide and the combination-therapy groups had semaglutide treatment for 16 weeks and then had either tablet placebo or empagliflozin added to the treatment, respectively, for a further 16 weeks; the placebo and empagliflozin groups were treated with the respective monotherapy for 32 weeks. Randomisation, administration of the study drugs and legal authority approvements are further outlined in the electronic supplementary material (ESM) Methods. All participants gave written informed consent.
The trial consisted of two parallel designs (Fig. 1): (1) a double-blind, placebo-controlled, randomised clinical trial to evaluate the effects of tablet empagliflozin 10 mg once daily (Jardiance; Boehringer Ingelheim International, Germany) vs matching placebo; and (2) a parallel-group intervention open-label trial of onceweekly subcutaneous injection of semaglutide 1 mg or highest tolerated dose (Ozempic; Novo Nordisk, Denmark) in combination with tablet empagliflozin or tablet placebo treatment (double-blinded tablet empagliflozin treatment). This resulted in four groups receiving either tablet placebo, empagliflozin, a combination of semaglutide and placebo (herein referred to as the 'semaglutide' group), or a combination of semaglutide and empagliflozin (herein referred to as the 'combination-therapy' group). The semaglutide and the combination-therapy groups had semaglutide treatment for 16 weeks and then had either tablet placebo or empagliflozin added to the treatment, respectively, for a further 16 weeks; the placebo and empagliflozin groups were treated with the respective monotherapy for 32 weeks. Randomisation, administration of the study drugs and legal authority approvements are further outlined in the electronic supplementary material (ESM) Methods. All participants gave written informed consent.
