Poster Presentation The Annual Scientific Meeting of the Australian Diabetes Society and the Australian Diabetes Educators Association 2013

ONCE-DAILY LIXISENATIDE AS ADD-ON TO BASAL INSULIN ± OADS IN PATIENTS WITH TYPE 2 DIABETES SELECTIVELY REDUCES POSTPRANDIAL HYPERGLYCEMIC DAYTIME EXPOSURE (#325)

David O'Neal 1 , Matthew Riddle 2 , Yutaka Seino 3 , Bertrand Cariou 4 , Ricardo Gómez-Huelgas 5 , Christine Roy-Duval 6 , Carole Hecquet 6 , Andres A DiGenio 7 , Julio Rosenstock 8
  1. St Vincent\'s Hospital (Melbourne), Fitzroy, Vic, Australia
  2. Oregon Health & Science University, Portland, OR, USA
  3. Kansai Electric Power Hospital, Osaka, Japan
  4. Department of Endocrinology, Nantes University Hospital, Nantes, France
  5. Medicina Interna Department, Hospital Carlos Haya, Málaga, Spain
  6. Sanofi, Paris, France
  7. Sanofi, Bridgewater, NJ, USA
  8. Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA
Basal insulin reduces basal hyperglycemia (BHG) but HbA1c may remain high due to persisting postprandial hyperglycemia (PPHG). Lixisenatide (LIXI), a GLP-1 receptor agonist in development for the treatment of Type 2 diabetes mellitus (T2DM), can reduce PPHG and HbA1c with no weight gain, or with weight loss, and thus has properties complementary to those of basal insulin. Patient-level data were pooled from three randomized Phase III studies of once-daily LIXI + standard of care (SOC; basal insulin ± oral agents) vs placebo (PBO) + SOC to quantify the effects of LIXI on BHG and PPHG exposures. BHG (24-hr area above 5.6 mmol/L and under the fasting level) and incremental PPHG (area above fasting and under self-monitored 7-point plasma glucose profiles [AUC24h]) exposures were calculated by a previously reported method. The 753 eligible patients had a mean age 57 years, BMI 29.8 kg/m2, diabetes duration 11.5 years, HbA1c 8.15% and fasting glucose 7.5 mmol/L. At baseline, mean daytime BHG and PPHG exposures were 49.2 and 55.1 mmol/L*h, respectively. Mean BHG and PPHG contributions to hyperglycemia were 42% and 58%, respectively. At Week 24, adjusted LS mean HbA1cchange was –0.77% with LIXI + SOC and –0.29% with PBO + SOC (p<0.0001). The BHG exposure values for LIXI + SOC and PBO + SOC were similar (adjusted LS mean change for AUC24h –13 mmol/L*h vs –11 mmol/L*h [NS]), but PPHG exposure was reduced more with LIXI + SOC compared with PBO + SOC (adjusted LS mean change –21 mmol/L*h vs –10 mmol/L*h, p<0.0001). The mean BHG and PPHG contributions to hyperglycemia were 46% vs 54% with LIXI + SOC and 39% vs 61% with PBO + SOC. In conclusion, this analysis suggests that once-daily LIXI complements the effects of basal insulin on glycemic control in T2DM, decreasing HbA1cmainly by reducing PPHG.