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)

Abstract

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.

Effects of DPP-4 Inhibitors on Blood Glucose Variability in Japanese Patients with Type 2 Diabetes on Maintenance Hemodialysis: A Prospective Observational Exploratory Study

“…Also, our data from the linear mixed-effects model showed a rapid BG drop during hemodialysis and a tendency for hypoglycemia in the subsequent nighttime period in maintenance hemodialysis patients with type 2 diabetes. Although DPP-4 inhibitors have been shown to improve BG variability in patients with type 2 diabetes in many randomized controlled trials (RCTs) [41][42][43][44][45][46][47][48][49] (see the table in the Electronic supplementary material), few studies have reported the same effect in maintenance hemodialysis patients [50]. Our study illustrates the usefulness of DPP-4 inhibitors in these patients.…”

“…The ability of DPP-4 inhibitors to suppress BG variability in patients with type 2 diabetes has been shown in studies using CGM [51, 52]. Furthermore, several RCTs using CGM found that BG variability is suppressed more effectively by DPP-4 inhibitors than by other agents such as sulfonylureas [41,42] and sodium glucose cotransporter 2 inhibitors [43][44][45] [41,49], or had used metformin only [41][42][43]46]. There have also been some reports on the usefulness of DPP-4 inhibitors in patients on hemodialysis [50], but none has shown obvious suppression of BG variability.…”

“…The ability of DPP-4 inhibitors to suppress BG variability in patients with type 2 diabetes has been shown in studies using CGM [ 51 , 52 ]. Furthermore, several RCTs using CGM found that BG variability is suppressed more effectively by DPP-4 inhibitors than by other agents such as sulfonylureas [ 41 , 42 ] and sodium glucose cotransporter 2 inhibitors [ 43 – 45 ] or by combination with insulin therapy [ 46 – 49 ]. The patients in these RCTs who showed suppressed BG variability with DPP-4 inhibitors had a mean age of less than 60 years [ 42 – 44 , 46 , 48 , 49 ], had HbA1c > 7% [ 41 – 44 , 46 – 49 ], were drug naïve [ 41 , 49 ], or had used metformin only [ 41 – 43 , 46 ].…”

A Comprehensive Review and Perspective on Natural Sources as Dipeptidyl Peptidase-4 Inhibitors for Management of Diabetes

“…DPP-4 inhibitors have been shown to decrease BG levels in T2DM patients by continuous glucose monitoring (CGM) [ 48 , 49 , 50 ]. In addition, various randomized controlled trials have shown by CGM that DPP-4 inhibitors suppress BG levels more efficiently than other agents such as sulfonylureas [ 51 , 52 ] or sodium glucose cotransporter 2 inhibitors [ 53 , 54 , 55 ] when used in combination with insulin administration [ 56 , 57 ]. DPP-4 inhibitors that enhance insulin secretion and decrease prandial glucagon levels have been shown to improve BG levels [ 49 ], and reductions in prandial glucagon levels are considered to underlie improvements in BG levels by DPP-4 inhibitors [ 58 ].…”

Impact of endogenous insulin secretion on the improvement of glucose variability in Japanese patients with type 2 diabetes treated with canagliflozin plus teneligliptin

“…In the present study, we carried out secondary analyses 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 (CALMER study) 5 to investigate the effect of combination therapy with dipeptidyl peptidase‐4 (DPP‐4) inhibitor and sodium–glucose cotransporter 2 (SGLT2) inhibitor in comparison with switching from DPP‐4 inhibitor to SGLT2 inhibitor on improving the GV in patients with or without impaired endogenous insulin secretion.…”