Trial design and baseline data for LIRA‐PRIME: A randomized trial investigating the efficacy of liraglutide in controlling glycaemia in type 2 diabetes in a primary care setting

Abstract

Aims Using a pragmatic approach, the LIRA‐PRIME trial aims to address a knowledge gap by comparing efficacy in controlling glycaemia with glucagon‐like peptide‐1 analog liraglutide vs oral antidiabetic drugs (OADs) in patients with type 2 diabetes (T2D) uncontrolled with metformin monotherapy in primary care practice. We report the study design and patient baseline characteristics. Materials and methods This 104‐week, two‐arm, open‐label, active‐controlled trial is active in 219 primary care practices across nine countries. At screening, eligible patients with T2D were at least 18 years of age, had been using a stable daily dose of metformin ≥1500 mg or the maximum tolerated dose for ≥60 days, and had a glycated haemoglobin (HbA1c) of 7.5% to 9.0%, measured ≤90 days before screening. Patients were randomized (1:1) to liraglutide or OAD, both in addition to pre‐trial metformin. Individual OADs were chosen by the treating physician based on local guidelines. The primary endpoint is time to inadequate glycaemic control, defined as HbA1c above 7.0% at two scheduled consecutive visits after the first 26 weeks of treatment. Results The trial randomized 1997 patients with a mean (standard deviation) age of 56.9 (10.8) years, T2D duration of 7.2 (5.9) years (range, <1‐47 years), and HbA1c of 8.2%. One‐fifth of patients had a history of diabetes complications, and most were overweight (24.8%) or had obesity (65.3%). Conclusions This pragmatically designed, large‐scale, multinational, randomized clinical trial will help guide treatment decisions for patients with T2D who are inadequately controlled with metformin monotherapy and treated in primary care.

Maintenance of glycaemic control with liraglutide versus oral antidiabetic drugs as add‐on therapies in patients with type 2 diabetes uncontrolled with metformin alone: A randomized clinical trial in primary care (LIRA‐PRIME)

“…Follow‐up visits were scheduled at weeks 2, 4, 16, and 26 after randomization and quarterly thereafter, to reflect the normal frequency of appointments in routine practice 12 . There was a 1‐week follow‐up period after the end of treatment (the visit schedule and assessments at each visit have been published previously) 12 . Race and ethnicity were recorded based on recommendations outlined by the US Food and Drug Administration 13 to allow comparison across trials.…”

“…Patients aged 18 years or older with T2D (HbA1c 7.5%‐9.0% [58.5‐74.9 mmol/mol]) were eligible if receiving a stable dose of metformin (≥1500 mg/d or maximum tolerated dose) as monotherapy for 60 days or longer before screening and met local criteria for use of liraglutide and OAD treatment 12 . Patients who were pregnant or breastfeeding and those who had received any diabetes medication other than metformin 60 days or less before screening were excluded.…”

“…Participants were selected from volunteers responding to posters or during interactions with their personal clinicians 12 . All patients provided written informed consent and were not remunerated for participation.…”

“…After a screening period of 2 weeks or less, patients were randomized (1:1) to subcutaneous liraglutide or an OAD (α‐glucosidase inhibitor, DPP‐4i, meglitinide, SGLT‐2i, SU, or thiazolidinedione), both added to metformin, for up to 104 weeks. 12 The allocated OAD was chosen by the investigator and was therefore not part of the randomization process. Doses of liraglutide were escalated from 0.6 to 1.2 mg/d up to a final dose of 1.8 mg/d.…”

“… 12 There was a 1‐week follow‐up period after the end of treatment (the visit schedule and assessments at each visit have been published previously). 12 Race and ethnicity were recorded based on recommendations outlined by the US Food and Drug Administration 13 to allow comparison across trials.…”