EFFICACY AND SAFETY OF ONCE-DAILY LIXISENATIDE ADDED ON TO TITRATED GLARGINE PLUS ORAL AGENTS IN TYPE 2 DIABETES: GETGOAL-DUO 1 STUDY — ASN Events
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  3. EFFICACY AND SAFETY OF ONCE-DAILY LIXISENATIDE ADDED ON TO TITRATED GLARGINE PLUS ORAL AGENTS IN TYPE 2 DIABETES: GETGOAL-DUO 1 STUDY

EFFICACY AND SAFETY OF ONCE-DAILY LIXISENATIDE ADDED ON TO TITRATED GLARGINE PLUS ORAL AGENTS IN TYPE 2 DIABETES: GETGOAL-DUO 1 STUDY (#64)

Julio Rosenstock 1 , Thomas Forst 2 , Ronnie Aronson 3 , Leobardo Sauque-Reyna 4 , Elisabeth Souhami 5 , Lin Ping 6 , Matthew Riddle 7
  1. Dallas Diabetes and Endocrine Center, Medical City, Dallas, TX, USA
  2. Institute for Clinical Research and Development, Mainz, Germany
  3. LMC Diabetes & Endocrinology, Ontario, CA, Canada
  4. Unidad Metabolica y Cardiovascular SC de Cuernavaca, Cuernavaca, Mexico
  5. Sanofi, Paris, France
  6. Sanofi, Bridgewater, NJ, USA
  7. Oregon Health and Science University, Portland, OR, USA

Lixisenatide is a once-daily GLP-1R agonist with robust postprandial effects that could complement basal insulin therapy. This randomised, double-blind, multicentre trial in patients with T2DM inadequately controlled on metformin ± SU ± TZDs assessed the efficacy and safety of lixisenatide added on to titrated insulin glargine + metformin ± TZDs [NCT00975286]. Glargine was initiated and titrated in a 12-wk run-in phase to achieve FPG 4.4-5.6 mmol/L. Subjects with HbA1c ≥7% and ≤9%, and whose mean FPG was ≤ 7.8 mmol/L were then randomised to once-daily lixisenatide 20 μg (n=223) or placebo (n=223) for 24 weeks while glargine titration continued. At run-in start, SU therapy was stopped and all subjects were on metformin; 12% were also on a TZD. Patient demographics were similar in both groups (mean age 56.2y, T2DM duration 9.2y, BMl 31.8 kg/m2). Primary endpoint was change in HbA1c from randomisation. HbA1c initially decreased during run-in from 8.6% to 7.6% and lixisenatide further reduced HbA1c by 0.71 versus 0.40% with placebo with consistent glargine titration at week 24 (LS mean difference: -0.32%; p<0.0001). Significantly more lixisenatide patients achieved HbA1c <7.0% (56% versus 39% with placebo; p=0.0001). Lixisenatide significantly improved 2-h PPG after a standardised breakfast and had a beneficial effect on body weight versus placebo (LS mean difference: -0.89 kg; p=0.0012) despite glargine titration.  AEs occurred in 80% of subjects on lixisenatide versus 68% on placebo; nausea/vomiting were more common with lixisenatide (27.4%/9.4% versus 4.9%/1.3%) and were also the most common AEs leading to discontinuation (total of 4·0 versus 0·0% with placebo).  Documented symptomatic hypoglycaemia (blood glucose <3.3 mmol/L) was reported in 20.2% of the lixisenatide-treated patients versus 11.7% on placebo.

In conclusion, lixisenatide added to consistently titrated insulin glargine plus OADs significantly improved HbA1c, reduced PPG and had a beneficial effect on weight with an expected GLP-1 AE profile that subsided over time.                                                                                                             

Two additional phase 3 trials have recently been completed that study the effects of adding lixisenatide to basal insulin; GetGoal-L [NCT00715624] and GetGoal-L Asia [NCT00866658].  Results of all three trials will be presented side by side to show where GetGoal-Duo 1 fits in the body of evidence for lixisenatide in combination with basal insulin.