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

Diabetes Obes Metab. 2025 Jan;27(1):81-91. doi: 10.1111/dom.15985. Epub 2024 Oct 7.

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.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Clinical Trial, Phase III

MeSH terms

  • Adult
  • Aged
  • Benzhydryl Compounds* / administration & dosage
  • Benzhydryl Compounds* / adverse effects
  • Benzhydryl Compounds* / therapeutic use
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Double-Blind Method
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Glucosides* / administration & dosage
  • Glucosides* / adverse effects
  • Glucosides* / therapeutic use
  • Glycated Hemoglobin* / analysis
  • Glycated Hemoglobin* / drug effects
  • Humans
  • Hypoglycemic Agents* / administration & dosage
  • Hypoglycemic Agents* / adverse effects
  • Hypoglycemic Agents* / therapeutic use
  • Linagliptin* / administration & dosage
  • Linagliptin* / adverse effects
  • Linagliptin* / therapeutic use
  • Male
  • Metformin* / administration & dosage
  • Metformin* / therapeutic use
  • Middle Aged
  • Treatment Outcome

Substances

  • Benzhydryl Compounds
  • Blood Glucose
  • dapagliflozin
  • Drug Combinations
  • Glucosides
  • Glycated Hemoglobin
  • hemoglobin A1c protein, human
  • Hypoglycemic Agents
  • Linagliptin
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT06329674