Efficacy and tolerability of novel triple combination therapy in drug-naïve patients with type 2 diabetes from the TRIPLE-AXEL trial: protocol for an open-label randomised controlled trial

Nam Hoon Kim, Soo Lim, Soo Heon Kwak, Min Kyong Moon, Jun Sung Moon, Yong-Ho Lee, Ho Chan Cho, Juneyoung Lee, Sin Gon Kim, Nam Hoon Kim, Soo Lim, Soo Heon Kwak, Min Kyong Moon, Jun Sung Moon, Yong-Ho Lee, Ho Chan Cho, Juneyoung Lee, Sin Gon Kim

Abstract

Introduction: Patients with type 2 diabetes are at risk of microvascular and macrovascular complications. Intensive glycaemic control, especially in patients with short duration of diabetes, is the mainstay of management of type 2 diabetes to lower the risk of complications. However, despite the improvement in the understanding of the pathophysiology of type 2 diabetes and development of novel glucose-lowering agents, long-term durable glycaemic control remains a difficult goal to achieve. Several challenging clinical trials proved that an early combination therapy with a variety of glucose-lowering agents had a more favourable effect than conventional stepwise therapy in terms of glycaemic control. We aim to evaluate the efficacy and tolerability of a novel, initial triple combination therapy with metformin, sodium glucose cotransporter 2 inhibitor (dapagliflozin) and dipeptidyl peptidase-4 inhibitor (saxagliptin) compared with conventional stepwise add-on therapy in drug-naïve patients with recent-onset type 2 diabetes.

Methods and analysis: This study is a multicentre, prospective, randomised, open-label, parallel group, comparator-controlled trial. A total of 104 eligible participants will be randomised to either the initial combination therapy group or the conventional stepwise add-on therapy group for 104 weeks. The primary endpoint is the proportion of patients who achieved haemoglobin A1c level<6.5% without hypoglycaemia, weight gain or discontinuation due to adverse events at 104 weeks. This trial will determine whether a novel triple combination therapy with metformin, dapagliflozin and saxagliptin has a beneficial effect on durable glycaemic control compared with conventional therapy in drug-naïve patients with type 2 diabetes.

Ethics and dissemination: This study protocol was approved by the local institutional review boards and independent ethics committees over the recruitment sites. Results of this study will be disseminated in scientific journals and scientific conferences.

Trial registration number: NCT02946632; Pre-results.

Keywords: clinical trials; therapeutics.

Conflict of interest statement

Competing interests: SGK has received funds for research, honoraria for speaking at meetings and has served on Advisory Boards for Astra Zeneca. NHK has received honoraria for speaking at meetings from Astra Zeneca.

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Overall study design. BMI, body mass index; HbA1c, haemoglobin A1c; T2DM, type 2 diabetes mellitus.

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