Liraglutide as add-on to sodium-glucose co-transporter-2 inhibitors in patients with inadequately controlled type 2 diabetes: LIRA-ADD2SGLT2i, a 26-week, randomized, double-blind, placebo-controlled trial

Lawrence Blonde, Lidia Belousova, Udi Fainberg, Pedro A Garcia-Hernandez, Sunil M Jain, Margit S Kaltoft, Ofri Mosenzon, Jalal Nafach, Mads Sundby Palle, Rosangela Rea, Lawrence Blonde, Lidia Belousova, Udi Fainberg, Pedro A Garcia-Hernandez, Sunil M Jain, Margit S Kaltoft, Ofri Mosenzon, Jalal Nafach, Mads Sundby Palle, Rosangela Rea

Abstract

Aim: To compare the effect of liraglutide or placebo added on to sodium-glucose co-transporter-2 inhibitor (SGLT2i) ± metformin on glycaemic control in patients with type 2 diabetes.

Materials and methods: Patients with type 2 diabetes on a stable SGLT2i dose ± metformin (with HbA1c 7.0%-9.5% and body mass index [BMI] ≥ 20 kg/m2 ) were randomized 2:1 to add-on liraglutide 1.8 mg/day or placebo in this parallel, double-blind, multinational trial. Primary and confirmatory secondary endpoints were changes in HbA1c and body weight from baseline to week 26, respectively. The proportions of patients achieving HbA1c (<7.0%) targets and safety events after week 26 were also assessed.

Results: Of 303 patients randomized (one in error), 280 completed treatment. Mean changes in HbA1c from baseline to week 26 with liraglutide (n = 202) and placebo (n = 100) were - 0.98% and - 0.30%, respectively (estimated treatment difference [ETD]: -0.68% [95% CI: -0.89, -0.48]; P < 0.001). Mean body weight changes from baseline were - 2.81 versus -1.99 kg, respectively (ETD: -0.82 kg [95% CI: -1.73, 0.09]; P = 0.077); 51.8% of liraglutide-treated patients achieved HbA1c < 7.0% versus 23.2% receiving placebo (odds ratio: 5.1 [95% CI: 2.67, 9.87]; P < 0.001). More patients treated with liraglutide reported ≥1 treatment-emergent adverse events (66.3%) versus placebo (47.0%).

Conclusions: Liraglutide significantly improved glycaemic control compared with placebo in patients with type 2 diabetes, insufficiently controlled with SGLT2is with/without metformin, with no unexpected safety findings.

Keywords: glucagon-like peptide-1; liraglutide; randomized trial; sodium-glucose co-transporter-2 inhibitor.

Conflict of interest statement

La.B. declares research support from Janssen, Lexicon, Merck, Novo Nordisk and Sanofi; speaker honoraria from Janssen, Novo Nordisk and Sanofi; consultant honoraria from AstraZeneca, Gilead, Janssen, Merck, Novo Nordisk and Sanofi. P.A.G.‐H. declares research support and honoraria from Amgen, Eli Lilly and Novo Nordisk. S.M.J. declares research support, speaker honorarium and advisory board membership from TOTALL Diabetes Hormone Institute. O.M. declares speaker's bureau honoraria and advisory board membership from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk and Sanofi; speaker's bureau honorarium from Bristol Myers Squibb. R.R. declares speaker's bureau membership from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck Sharp & Dohme, Novo Nordisk, Sanofi and Takeda; research support from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi; consulting fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Sanofi. U.F., M.S.K. and M.S.P. are employees of Novo Nordisk. Li.B. and J.N. declare no conflicts of interest.

© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Change from baseline in HbA1c and body weight at week 26. (A) Mean HbA1c levels over 26 weeks, (B) HbA1c treatment effect at week 26 based on the in‐trial observation period, (C) mean body weight over 26 weeks, and (D) body weight treatment effect at week 26 based on the in‐trial observation period. Estimated treatment effect was calculated using treatment policy estimands with a pattern mixture model (PMM), which were based on the in‐trial observation period, including the effect of any rescue medication, regardless of whether patients prematurely discontinued trial product. Trial product estimands calculated using mixed model of repeated measurements (MMRMs) were based on the on‐treatment without rescue medication observation period. Error bars represent the standard error. ETD, estimated treatment difference
Figure 2
Figure 2
Proportion of patients reaching HbA1c targets and composite endpoints from baseline to 26 weeks (based on the in‐trial observation period)*. (A) Patients reaching an HbA1c target of

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Source: PubMed

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