Efficacy and safety of a fixed-dose combination of dapagliflozin and linagliptin (AJU-A51) in patients with type 2 diabetes mellitus: A multicentre, randomized, double-blind, parallel-group, placebo-controlled phase III study

Abstract

Aims: To evaluate the efficacy and safety of add-on dapagliflozin in patients with type 2 diabetes mellitus (T2D) who had inadequate glycaemic control with metformin and linagliptin.

Materials and methods: A total of 235 patients with inadequate response to metformin (≥1000 mg/day) plus linagliptin (5 mg/day) were randomized to receive either dapagliflozin/linagliptin fixed-dose combination (FDC [AJU-A51]) 10/5 mg/day (n = 117) or linagliptin 5 mg plus placebo (n = 118) for 24 weeks. After the main treatment period, patients who received linagliptin plus placebo were treated with AJU-A51 for an additional 28 weeks. Change in glycated haemoglobin (HbA1c) from baseline to Week 24 was the primary endpoint.

Results: AJU-A51 significantly reduced HbA1c levels (from 7.93% ± 0.82% to 7.11% ± 0.61%) compared with linagliptin plus placebo (from 7.80% ± 0.71% to 7.87% ± 0.94%), with a least squares mean difference of -0.88% (95% confidence interval -1.07 to -0.68; p < 0.0001) at 24 weeks. The AJU-A51 group had a significantly higher proportion of patients who achieved HbA1c <7.0% at Week 24 than the control group (44.8% vs. 18.6%; p < 0.001). The AJU-A51 group maintained glycaemic efficacy up to 52 weeks, whereas the control group showed a substantial reduction in HbA1c after switching to AJU-A51 in the extension study period. Both groups had similar incidence of treatment-emergent and serious adverse events, and no cases of symptomatic hypoglycaemia were reported.

Conclusions: Dapagliflozin and linagliptin FDC (AJU-A51) showed potent glucose-lowering effects, with good tolerability, in patients with T2D who had poor glycaemic control on metformin and linagliptin (ClinicalTrials.gov [NCT06329674]).

Keywords: SGLT2 inhibitor; dapagliflozin; linagliptin; randomized controlled trial; type 2 diabetes.

FIGURE 1

Study enrolment flowchart. ^†AJU‐A51 refers to dapagliflozin/linagliptin fixed‐dose combination. ^‡Adverse events other than hypoglycaemia and abnormal liver enzyme levels. ^§All 13 subjects were excluded from the full analysis set (FAS) because of the absence of follow‐up glycated haemoglobin results after baseline examination.

FIGURE 2

Glycaemic outcomes. (A) Changes in glycated haemoglobin (HbA1c) and (B) fasting plasma glucose (FPG) levels from baseline. (C) Achieved target glycaemic goals of HbA1c at Week 24. (A and B) Values at each time point are presented as mean ± standard error. (C) Values are presented as percentage (%). ^†AJU‐A51 refers to dapagliflozin/linagliptin fixed‐dose combination. ^‡Extension study: participants were additionally administered with AJU‐A51 for 28 weeks regardless of the group assigned in the main study. ^§Differences in changes between the two groups are reported as least squares mean (95% confidence interval).

FIGURE 3

Metabolic and lipid outcomes. Changes in (A) homeostatic model assessment of insulin resistance (HOMA‐IR), (B) homeostatic model assessment index of beta‐cell function (HOMA‐β), (C) body weight, (D) triglycerides (TG), (E) high‐density lipoprotein cholesterol (HDL‐C), and (F) low‐density lipoprotein cholesterol (LDL‐C) levels from baseline to 24 weeks. Values at each time point are presented as mean ± standard deviation. ^†AJU‐A51 refers to dapagliflozin/linagliptin fixed‐dose combination.