Original research| Volume 9, ISSUE 1, P15-22, February 2015

Download started.


Design and methods of a randomised double-blind trial of adding liraglutide to control HbA1c in patients with type 2 diabetes with impaired glycaemic control treated with multiple daily insulin injections (MDI-Liraglutide trial)

Published:August 28, 2014DOI:


      • The first study of its kind on incretin-based therapy together with MDI therapy.
      • The majority of the studied patient group can be found in primary care settings.
      • Glycaemic variability will be evaluated by masked continuous glucose monitoring.



      Patients with type 2 diabetes are generally treated in primary care setting and as a final treatment step to obtain good glycaemic control, multiple daily insulin injections (MDI) are generally used. The aim of this study is to evaluate the effect of GLP-1 analogue liraglutide on glycaemic control in patients with type 2 diabetes treated with MDI with inadequate glycaemic control.


      Overweight and obese patients with type 2 diabetes and impaired glycaemic control treated with MDI were randomised to liraglutide or placebo over 24 weeks. Masked continuous glucose monitoring was performed at baseline and during the trial. The primary endpoint was the change in haemoglobin A1c from baseline to week 24. Additional endpoints include changes in weight, fasting glucose, glycaemic variability, treatment satisfaction, insulin dose, hypoglycaemias, blood pressure and blood lipid levels.


      Recruitment occurred between February 2013 and February 2014. A total of 124 patients were randomised. Study completion is anticipated in August 2014.


      It is expected that the results of this study will establish whether adding liraglutide to patients with type 2 diabetes treated with MDI will improve glycaemic control, lower body weight, and influence glycaemic variability.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Primary Care Diabetes
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • UK Prospective Diabetes Study Group
        Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).
        Lancet. 1998; 352: 837-853
        • Holman R.R.
        • Paul S.K.
        • Bethel M.A.
        • et al.
        10-Year follow-up of intensive glucose control in type 2 diabetes.
        N. Engl. J. Med. 2008; 359: 1577-1589
        • Lind M.
        • Olsson M.
        • Rosengren A.
        • et al.
        The relationship between glycaemic control and heart failure in 83,021 patients with type 2 diabetes.
        Diabetologia. 2012; 55: 2946-2953
        • American Diabetes Association
        Standards of medical care in diabetes – 2010.
        Diabetes Care. 2010; 33: S11-S61
        • National Board of Health and Welfare
        Nationella Riktlinjer för diabetesvården.
        2010 ( (accessed 14.05.14))
        • Inzucchi S.E.
        • Bergenstal R.M.
        • Buse J.B.
        • et al.
        Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
        Diabetologia. 2012; 55: 1577-1596
        • Lind M.
        • Pivodic A.
        • Cea-Soriano L.
        • et al.
        Changes in HbA1c and frequency of measuring HbA1c and adjusting glucose-lowering medications in the 10 years following diagnosis of type 2 diabetes: a population-based study in the UK.
        Diabetologia. 2014; May (Epub ahead of print)
        • Pi-Sunyer F.X.
        The impact of weight gain on motivation, compliance, and metabolic control in patients with type 2 diabetes mellitus.
        Postgrad. Med. 2009; 121: 94-107
        • Ahrén B.
        Insulin plus incretin: a glucose-lowering strategy for type 2-diabetes.
        World J. Diabetes. 2014; 5: 40-51
        • Lind M.
        • Jendle J.
        • Torffvit O.
        • Lager I.
        Glucagon-like peptide 1 (GLP-1) analogue combined with insulin reduces HbA1c and weight with low risk of hypoglycemia and high treatment satisfaction.
        Prim. Care Diabetes. 2012; 6: 41-46
        • Hirsch I.B.
        Clinical review: realistic expectations and practical use of continuous glucose monitoring for the endocrinologist.
        J. Clin. Endocrinol. Metab. 2009; 94: 2232-2238
        • Workgroup on Hypoglycemia
        • American Diabetes Association
        Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia.
        Diabetes Care. 2005; 28: 1245-1249
        • Lind M.
        Incretin therapy and its effect on body weight in patients with diabetes.
        Prim. Care Diabetes. 2012; 6: 187-191
        • Lane W.
        • Weinrib S.
        • Rappaport J.
        • Hale C.
        The effect of addition of liraglutide to high-dose intensive insulin therapy: a randomized prospective trial.
        Diabetes Obes. Metab. 2014; March (Epub ahead of print)
        • Fonseca V.
        • Schweizer A.
        • Albrecht D.
        • et al.
        Addition of vildagliptin to insulin improves glycaemic control in type 2 diabetes.
        Diabetologia. 2007; 50: 1148-1155
        • Kothny W.
        • Foley J.
        • Kozlovski P.
        • et al.
        Improved glycaemic control with vildagliptin added to insulin, with or without metformin, in patients with type 2 diabetes mellitus.
        Diabetes Obes. Metab. 2013; 15: 252-257
        • Vilsbøll T.
        • Rosenstock J.
        • Yki-Järvinen H.
        • et al.
        Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes.
        Diabetes Obes. Metab. 2010; 12: 167-177
        • Yki-Järvinen H.
        • Rosenstock J.
        • Durán-Garcia S.
        • et al.
        Effects of adding linagliptin to basal insulin regimen for inadequately controlled type 2 diabetes: a ≥52-week randomized, double-blind study.
        Diabetes Care. 2013; 36: 3875-3881
        • Buse J.B.
        • Bergenstal R.M.
        • Glass L.C.
        • et al.
        Use of twice-daily exenatide in basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial.
        Ann. Intern. Med. 2011; 154: 103-112
        • Riddle M.C.
        • Aronson R.
        • Home P.
        • et al.
        Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebocontrolled comparison (GetGoal-L).
        Diabetes Care. 2013; 36: 2489-2496
        • Riddle M.C.
        • Forst T.
        • Aronson R.
        • et al.
        Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine: a 24-week, randomized, placebo-controlled study (GetGoal-Duo 1).
        Diabetes Care. 2013; 36: 2497-2503
        • Seino Y.
        • Min K.W.
        • Niemoeller E.
        • Takami A.
        Randomized, double-blind, placebo-controlled trial of the once-daily GLP-1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea (GetGoal-L-Asia).
        Diabetes Obes. Metab. 2012; 14: 910-917
        • Pratley R.E.
        • Nauck M.
        • Bailey T.
        • et al.
        • 1860-LIRA-DPP-4 Study Group
        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.
        Lancet. 2010; 375: 1447-1456
        • Buse J.B.
        • Rosenstock J.
        • Sesti G.
        • 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).
        Lancet. 2009; 374: 39-47