Improvement in glycated haemoglobin evaluated by baseline body mass index: a meta‐analysis of the liraglutide phase III clinical trial programme

In the liraglutide clinical trial programme, liraglutide 1.2 and 1.8 mg were found to effectively lower glycated haemoglobin (HbA1c) in patients with type 2 diabetes (T2D). It is unknown whether baseline body mass index (BMI) is a predictor of change in HbA1c observed during a clinical trial with liraglutide or placebo treatment. The present meta‐analysis of patient‐level data, using pooled data from seven phase III trials [LEAD‐1–6 and the liraglutide versus sitagliptin trial (LIRA–DPP‐4)] for liraglutide 1.2, 1.8 mg and placebo (n = 3222), identified no significant correlation between baseline BMI (<20 kg/m2 up to 45 kg/m2) and HbA1c reduction for placebo or liraglutide 1.2 mg, and a modest, clinically non‐relevant, association for liraglutide 1.8 mg [−0.010 (95% confidence interval −0.020, −0.001)], whereby a 10 kg/m2 increase in baseline BMI corresponded to 0.10%‐point (1.1 mmol/mol) greater HbA1c reduction. In summary, reductions in HbA1c obtained during clinical trials with liraglutide or placebo treatment were independent of baseline BMI.

[1]  D. Matthews,et al.  Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes , 2015, Diabetologia.

[2]  D. Matthews,et al.  Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach: Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes , 2014, Diabetes Care.

[3]  M. Ganz,et al.  Clinical Effectiveness of Liraglutide Across Body Mass Index in Patients with Type 2 Diabetes in the United States: A Retrospective Cohort Study , 2014, Advances in Therapy.

[4]  Murray Stewart,et al.  Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study. , 2014, The lancet. Diabetes & endocrinology.

[5]  M. Nauck,et al.  The Effect of Liraglutide on A1C and Body Weight is Largely Independent of Diabetes Duration , 2013 .

[6]  B. Zinman,et al.  Weight change with liraglutide and comparator therapies: an analysis of seven phase 3 trials from the liraglutide diabetes development programme , 2013, Diabetes, obesity & metabolism.

[7]  D. Jonker,et al.  Dosing Rationale for Liraglutide in Type 2 Diabetes Mellitus: A Pharmacometric Assessment , 2012, Journal of clinical pharmacology.

[8]  B. Hoogwerf,et al.  Baseline Factors Associated With Glycemic Control and Weight Loss When Exenatide Twice Daily Is Added to Optimized Insulin Glargine in Patients With Type 2 Diabetes , 2012, Diabetes Care.

[9]  R. Cuddihy,et al.  Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial , 2010, The Lancet.

[10]  A. Vaag,et al.  Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial , 2009, Diabetologia.

[11]  J. Rosenstock,et al.  Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6) , 2009, The Lancet.

[12]  B. Zinman,et al.  Efficacy and Safety of the Human Glucagon-Like Peptide-1 Analog Liraglutide in Combination With Metformin and Thiazolidinedione in Patients With Type 2 Diabetes (LEAD-4 Met+TZD) , 2009, Diabetes Care.

[13]  S. Colagiuri,et al.  Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU) , 2009, Diabetic medicine : a journal of the British Diabetic Association.

[14]  B. Bode,et al.  Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial , 2009, The Lancet.

[15]  Y. Yoshitoshi [Obesity and metabolism]. , 1967, Nihon Ishikai zasshi. Journal of the Japan Medical Association.

[16]  A. Winship Interest. , 1893 .