Journal Article

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

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

2018

Overview

IntroductionPatients 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 analysisThis 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 disseminationThis 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.

• Publisher: BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adamantane - administration & dosage / Adamantane - adverse effects / Adamantane - analogs & derivatives / Adult / Benzhydryl Compounds - administration & dosage / Benzhydryl Compounds - adverse effects / Body mass index / Cardiovascular disease / Combination therapy / Diabetes / Diabetes and Endocrinology / Diabetes Complications - prevention & control / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - therapy / Dipeptides - administration & dosage / Dipeptides - adverse effects / Drug dosages / Drug Monitoring - methods / Drug Monitoring - standards / Drug Therapy, Combination - methods / Glucagon / Glucose / Glucosides - administration & dosage / Glucosides - adverse effects / Glycated Hemoglobin - analysis / Hemoglobin / Humans / Hyperglycemia / Hypoglycemia / Hypoglycemic Agents - administration & dosage / Hypoglycemic Agents - adverse effects / Insulin / Male / Metformin - administration & dosage / Metformin - adverse effects / Multicenter Studies as Topic / Physicians / Prospective Studies / Randomized Controlled Trials as Topic / Treatment Outcome / Vital signs / Womens health