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