Comparison of protective effects of teneligliptin and luseogliflozin on pancreatic β-cell function: randomized, parallel-group, multicenter, open-label study (SECRETE-I study)

Abstract

Aims: The aim of this study is to directly compare the effects of SGLT2 inhibitors and DPP-4 inhibitors on β-cell function in patients with type 2 diabetes.

Materials and methods: We conducted a 26-week, randomized, open-label, parallel-group study, including a 1-2 week drug washout period, in patients with type 2 diabetes with HbA1c ≥7.0% and <9.0% and BMI ≥20 kg/m² despite treatment with a drug naïve or other than DPP-4 inhibitors or SGLT2 inhibitors. A total of 103 subjects were randomly assigned to receive once daily oral luseogliflozin (L) or teneligliptin (T). The primary endpoint was the effect of L vs. T on the change in logarithmus naturalis (Ln) disposition index (DI) (DI _0-120min; combining measures of insulin secretion and sensitivity) from baseline to week 25-26 (post intervention), which was calculated by conducting an oral glucose tolerance test.

Results: Ln DI _0-120min were improved in both groups: -0.46 ± 0.68 to -0.20 ± 0.59 (p=0.03) in L group and -0.26 ± 0.60 to -0.05 ± 0.62 (p=0.01) in T group. The change in Ln serum proinsulin/C-peptide ratio, a marker of β-cell dysfunction, was reduced in L group (1.63 ± 0.63 to 1.56 ± 0.68, p=0.16), but rather increased in T group (1.70 ± 0.75 to 1.90 ± 0.51, p=0.01), with significant difference between the two groups (-0.27; p=0.004).

Conclusions: Improvement of disposition index in subjects with obese type 2 diabetes was comparable between luseogliflozin and teneligliptin. On the other hand, it is likely that alleviation of β-cell dysfunction is more effective with luseogliflozin compared to tenegliptin.

Clinical trial registration: https://rctportal.niph.go.jp/en, identifier jRCTs061190008.

Keywords: DPP-4 inhibitor; SGLT2 inhibitor; proinsulin; type 2 diabetes; β-cell function.

Figure 1

Participant flow. The white square notes the reason for the exclusion. #1. COVID-19; Coronavirus Disease 2019.

Figure 2

Study procedure. * If the HbA1c level is 7% or higher after 12 weeks of intervention, the drug dosage is increased by the attending physician’s decision, paying attention to side effects in accordance with the package insert.

Figure 3

Changes in disposition index (DI), insulinogenic index (II) and Matsuda index after intervention with luseogliflozin or teneligliptin. Each figure (A-F) indicates DI (insulin) _0-120min. (A, B), II (insulin) _0-120min. (C, D), Matsuda index (E, F). Changes over time from baseline (A, C, E) and the amount of change (B, D, F; post-washout values minus values at baseline) are shown. Parameters that were non-normally distributed are shown as natural logarithms. # p<0.05 vs. baseline, *p<0.001 vs. baseline.

Figure 4

Changes in each parameter during oral glucose tolerance test and serum proinsulin/C-peptide ratio performed at baseline and after drug washout. Each figure (A-C) shows blood glucose (A), serum C-peptide (B), and serum insulin (C) levels during the oral glucose tolerance test. Solid black circle; luseogliflozin group at baseline, solid gray line; teneligliptin group at baseline, dotted black circle; luseogliflozin group after washout, dotted gray line; teneligliptin group after washout (A, B, C). (D) Change in serum proinsulin/C-peptide ratio in each group. Solid black circle; luseogliflozin group, solid gray line; teneligliptin group. (E) Amount of change in serum proinsulin/C-peptide ratio in each group. Black bars; luseogliflozin group, gray bars; teneligliptin group. Parameters that were non-normally distributed are shown as natural logarithms. * p<0.05, ** p<0.005: baseline vs. after washout in luseogliflozin group, # p<0.05, ## p<0.005: baseline vs. after washout in teneligliptin group. § p<0.005: luseogliflozin vs. teneligliptin.

Figure 5

Change in HbA1c levels and body weight during the intervention period in each group. (A, C) Change in HbA1c levels (A) and body weight (C) in each group. Solid black circle; luseogliflozin group, solid gray line; teneligliptin group. (B, D) Amount of change in HbA1c levels (B) and body weight (D) in each group. Black bars; luseogliflozin group, gray bars; teneligliptin group. * p<0.001 vs. baseline in luseogliflozin group, # p<0.001 vs. baseline in teneligliptin group, § p<0.05, §§ p<0.001 luseogliflozin. vs. teneligliptin.