Efficacy of liraglutide added to sodium-glucose cotransporter-2 inhibitors in type 2 diabetes, stratified by baseline characteristics: Post-hoc analysis of LIRA-ADD2SGLT2i

Abstract

Aims: The LIRA-ADD2SGLT2i trial demonstrated that liraglutide + sodium-glucose cotransporter-2 inhibitors (SGLT2is) ± metformin significantly improved glycaemic control (not body weight) versus placebo in adults with type 2 diabetes (T2D). This post-hoc analysis assessed whether baseline characteristics influenced these findings.

Materials and methods: LIRA-ADD2SGLT2i (NCT02964247) was a placebo-controlled, double-blind, multinational trial, wherein participants received liraglutide (≤1.8 mg/day) or placebo (randomized 2:1). Changes from baseline to week 26 in haemoglobin A1c (HbA1c), body weight and waist circumference stratified by HbA1c, body mass index (BMI), diabetes duration, duration of pre-trial SGLT2i use and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were analysed. These five baseline characteristics were divided into tertiles, and the treatment effect was evaluated using the trial product estimand.

Results: Data from all 303 participants were analysed. There was a significant interaction between baseline HbA1c tertiles (7.0%-<7.6%; 7.6%-8.1%; ≥8.2%-9.5%) and glycaemic control at week 26 (p_{[interaction]} = .011), with the lowest HbA1c estimated treatment difference (95% confidence interval) observed in patients with lowest baseline HbA1c [-0.20% (-0.59, 0.19); -0.68% (-1.03, -0.33); -0.98% (-1.33, -0.64), respectively]. There were no significant interactions in glycaemic control across baseline BMI, diabetes duration, insulin resistance determined by HOMA-IR or SGLT2i use duration (p_{[interaction]} > .05, all). Across the five characteristics assessed, no significant interactions were found for body weight or waist circumference changes from baseline (p_{[interaction]} > .05, all).

Conclusion: For individuals with T2D and inadequate glycaemic control despite therapy with SGLT2is ± metformin, liraglutide 1.8 mg would provide an effective treatment intensification option, irrespective of HbA1c, BMI, diabetes duration, insulin resistance determined by HOMA-IR and SGLT2i use duration.

Keywords: GLP-1 analogue; SGLT2 inhibitor; antidiabetic drug; glycaemic control; liraglutide; type 2 diabetes.

FIGURE 1

Scatterplot including correlations between overall changes in HbA1c from baseline to week 26 with the addition of liraglutide 1.8 mg versus placebo in patients with type 2 diabetes on stable sodium‐glucose cotransporter‐2 inhibitor therapy ± metformin (trial product estimand). A positive value on the vertical axis represents a reduction in HbA1c. Horizontal axis shows increasing baseline HbA1c values. HbA1c, glycated haemoglobin

FIGURE 2

Scatterplots and correlation between overall changes in body weight from baseline to week 26 with the addition of liraglutide 1.8 mg versus placebo in patients with type 2 diabetes on stable sodium‐glucose cotransporter‐2 inhibitor therapy ± metformin (trial product estimand). A positive value on the vertical axis represents a reduction in body weight. Horizontal axis shows increasing baseline BMI values. BMI, body mass index