Favourable effect of the sodium‐glucose co‐transporter‐2 inhibitor canagliflozin plus the dipeptidyl peptidase‐4 inhibitor teneligliptin in combination on glycaemic fluctuation: An open‐label, prospective, randomized, parallel‐group comparison trial (the CALMER study)

This multicentre, prospective, randomized, open‐label, blinded‐endpoint, parallel‐group, short‐term (4–5 weeks) controlled trial was conducted to investigate the superiority of the effect of reducing mean amplitude of glycaemic excursions (MAGE) during meal tolerance tests (MTTs) for the combination of dipeptidyl peptidase‐4 (DPP‐4) inhibitor and sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor compared with SGLT2 inhibitor monotherapy. Ninety‐nine patients with type 2 diabetes who were taking teneligliptin (20 mg/d) were randomized to one of the following two groups: those who switched to 100 mg/d of canagliflozin (SWITCH group) or those who added 100 mg/d of canagliflozin (COMB group). MAGE in the COMB group was significantly decreased compared with that in the SWITCH group (COMB 117.5 ± 39.8 to 92.2 ± 28.0 mg/dL vs SWITCH 110.7 ± 29.8 to 104.2 ± 27.6 mg/dL; P<0.01). Mean blood glucose decreased significantly during MTTs in both groups, although the extent of the reduction was significantly greater in the COMB group (COMB 142.3 ± 28.7 to 119.5 ± 25.1 mg/dL vs SWITCH 146.4 ± 25.5 to 135.5 ± 22.4 mg/dL; P < 0.01). SGLT2 inhibitor combined with DPP‐4 inhibitor therapy strongly reduced glycaemic fluctuation compared with SGLT2 inhibitor monotherapy.