PMID- 25887358
OWN - NLM
STAT- MEDLINE
DCOM- 20160126
LR  - 20221207
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Linking)
VI  - 38
IP  - 7
DP  - 2015 Jul
TI  - Contrasting Effects of Lixisenatide and Liraglutide on Postprandial Glycemic 
      Control, Gastric Emptying, and Safety Parameters in Patients With Type 2 Diabetes 
      on Optimized Insulin Glargine With or Without Metformin: A Randomized, Open-Label 
      Trial.
PG  - 1263-73
LID - 10.2337/dc14-1984 [doi]
AB  - OBJECTIVE: This mechanistic trial compared the pharmacodynamics and safety of 
      lixisenatide and liraglutide in combination with optimized insulin glargine 
      with/without metformin in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: 
      This was a multicenter, randomized, open-label, three-arm trial comparing 
      lixisenatide 20 microg and liraglutide 1.2 and 1.8 mg once daily for 8 weeks in 
      combination with insulin glargine after optimized titration. The primary end 
      point was change from baseline to week 8 in incremental area under the 
      postprandial plasma glucose curve for 4 h after a standardized solid breakfast 
      (AUC PPG0030-0430 h). Changes from baseline in gastric emptying, 24-h plasma 
      glucose profile, HbA1c, fasting plasma glucose (FPG), 24-h ambulatory heart rate 
      and blood pressure, amylase and lipase levels, and adverse events (AEs) were also 
      assessed. RESULTS: In total, 142 patients were randomized and treated. 
      Lixisenatide 20 microg achieved greater reductions of AUC PPG0030-0430 h compared 
      with liraglutide (marginal mean [95% one-sided CI] treatment difference, -6.0 
      [-7.8] h ⋅ mmol/L [-108.3 (-140.0) h ⋅ mg/dL] vs. liraglutide 1.2 mg and -4.6 
      [-6.3] h ⋅ mmol/L [-83.0 (-114.2) h ⋅ mg/dL] vs. liraglutide 1.8 mg; P < 0.001 
      for both), and gastric emptying was delayed to a greater extent than with 
      liraglutide 1.2 and 1.8 mg (P < 0.001 for treatment comparisons). FPG was 
      unchanged in all treatment arms. At week 8, mean +/- SD HbA1c was 6.2 +/- 0.4% (44 +/- 
      5 mmol/mol), 6.1 +/- 0.3% (44 +/- 4 mmol/mol), and 6.1 +/- 0.3% (44 +/- 4 mmol/mol) for 
      lixisenatide 20 microg and liraglutide 1.2 and 1.8 mg, respectively. At week 8, both 
      liraglutide doses increased marginal mean +/- SE 24-h heart rate from baseline by 9 
      +/- 1 bpm vs. 3 +/- 1 bpm with lixisenatide (P < 0.001). Occurrence of symptomatic 
      hypoglycemia was higher with lixisenatide; gastrointestinal AEs were more common 
      with liraglutide. Lipase levels were significantly increased from baseline with 
      liraglutide 1.2 and 1.8 mg (marginal mean +/- SE increase 21 +/- 7 IU/L for both; P < 
      0.05). CONCLUSIONS: Lixisenatide and liraglutide improved glycemic control in 
      optimized insulin glargine-treated T2D albeit with contrasting mechanisms of 
      action and differing safety profiles.
CI  - (c) 2015 by the American Diabetes Association. Readers may use this article as long 
      as the work is properly cited, the use is educational and not for profit, and the 
      work is not altered.
FAU - Meier, Juris J
AU  - Meier JJ
AD  - Diabetes Division, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany 
      juris.meier@rub.de.
FAU - Rosenstock, Julio
AU  - Rosenstock J
AD  - Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX.
FAU - Hincelin-Mery, Agnes
AU  - Hincelin-Mery A
AD  - Sanofi R&D, Chilly-Mazarin, France.
FAU - Roy-Duval, Christine
AU  - Roy-Duval C
AD  - Sanofi R&D, Chilly-Mazarin, France.
FAU - Delfolie, Astrid
AU  - Delfolie A
AD  - Sanofi R&D, Chilly-Mazarin, France.
FAU - Coester, Hans-Veit
AU  - Coester HV
AD  - Profil, Neuss, Germany.
FAU - Menge, Bjoern A
AU  - Menge BA
AD  - Diabetes Division, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
FAU - Forst, Thomas
AU  - Forst T
AD  - Profil, Mainz, Germany.
FAU - Kapitza, Christoph
AU  - Kapitza C
AD  - Profil, Neuss, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT01596504
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150417
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Peptides)
RN  - 2ZM8CX04RZ (Insulin Glargine)
RN  - 74O62BB01U (lixisenatide)
RN  - 839I73S42A (Liraglutide)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Adult
MH  - Blood Glucose/drug effects
MH  - Diabetes Mellitus, Type 2/*drug therapy/physiopathology
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Gastric Emptying/drug effects
MH  - Glycated Hemoglobin/drug effects
MH  - Humans
MH  - Hypoglycemia/chemically induced
MH  - Hypoglycemic Agents/*administration & dosage
MH  - Insulin Glargine/administration & dosage
MH  - Liraglutide/*administration & dosage
MH  - Male
MH  - Metformin/administration & dosage
MH  - Middle Aged
MH  - Peptides/*administration & dosage
MH  - Postprandial Period/drug effects
MH  - Treatment Outcome
EDAT- 2015/04/19 06:00
MHDA- 2016/01/27 06:00
CRDT- 2015/04/19 06:00
PHST- 2014/08/18 00:00 [received]
PHST- 2015/03/16 00:00 [accepted]
PHST- 2015/04/19 06:00 [entrez]
PHST- 2015/04/19 06:00 [pubmed]
PHST- 2016/01/27 06:00 [medline]
AID - dc14-1984 [pii]
AID - 10.2337/dc14-1984 [doi]
PST - ppublish
SO  - Diabetes Care. 2015 Jul;38(7):1263-73. doi: 10.2337/dc14-1984. Epub 2015 Apr 17.