PMID- 32295808
OWN - NLM
STAT- MEDLINE
DCOM- 20210304
LR  - 20221207
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Print)
IS  - 0149-5992 (Linking)
VI  - 43
IP  - 6
DP  - 2020 Jun
TI  - Efficacy and Safety of 1:1 Fixed-Ratio Combination of Insulin Glargine and 
      Lixisenatide Versus Lixisenatide in Japanese Patients With Type 2 Diabetes 
      Inadequately Controlled on Oral Antidiabetic Drugs: The LixiLan JP-O1 Randomized 
      Clinical Trial.
PG  - 1249-1257
LID - 10.2337/dc19-2452 [doi]
AB  - OBJECTIVE: To assess the efficacy and safety of a 1:1 fixed-ratio combination of 
      insulin glargine and lixisenatide (iGlarLixi) versus lixisenatide (Lixi) in 
      insulin-naive Japanese patients with type 2 diabetes mellitus (T2DM) inadequately 
      controlled on oral antidiabetic drugs (OADs). RESEARCH DESIGN AND METHODS: In 
      this phase 3, open-label, multicenter trial, 321 patients with HbA(1c)>/=7.5 to 
      </=10.0% (58-86 mmol/mol) and fasting plasma glucose (FPG) </=13.8 mmol/L (250 mg/dL) 
      were randomized 1:1 to iGlarLixi or Lixi for 52 weeks. The primary end point was 
      change in HbA(1c) at week 26. RESULTS: Change in HbA(1c) from baseline to week 26 
      was significantly greater with iGlarLixi (-1.58% [-17.3 mmol/mol]) than with Lixi 
      (-0.51% [-5.6 mmol/mol]), confirming the superiority of iGlarLixi (least squares 
      [LS] mean difference -1.07% [-11.7 mmol/mol], P < 0.0001). At week 26, 
      significantly greater proportions of patients treated with iGlarLixi reached 
      HbA(1c) <7% (53 mmol/mol) (65.2% vs. 19.4%; P < 0.0001), and FPG reductions were 
      greater with iGlarLixi than Lixi (LS mean difference -2.29 mmol/L [-41.23 mg/dL], 
      P < 0.0001). Incidence of documented symptomatic hypoglycemia (</=3.9 mmol/L [70 
      mg/dL]) was higher with iGlarLixi (13.0% vs. 2.5%) through week 26, with no 
      severe hypoglycemic events in either group. Incidence of gastrointestinal events 
      through week 52 was lower with iGlarLixi (36.0% vs. 50.0%), and rates of 
      treatment-emergent adverse events were similar. CONCLUSIONS: This phase 3 study 
      demonstrated superior glycemic control and fewer gastrointestinal adverse events 
      with iGlarLixi than with Lixi, which may support it as a new treatment option for 
      Japanese patients with T2DM that is inadequately controlled with OADs.
CI  - (c) 2020 by the American Diabetes Association.
FAU - Watada, Hirotaka
AU  - Watada H
AUID- ORCID: 0000-0001-5961-1816
AD  - Department of Metabolism and Endocrinology, Juntendo University Graduate School 
      of Medicine, Tokyo, Japan hwatada@juntendo.ac.jp.
FAU - Takami, Akane
AU  - Takami A
AD  - Research & Development, Sanofi K.K., Tokyo, Japan.
FAU - Spranger, Robert
AU  - Spranger R
AD  - Diabetes, Cardiovascular and Metabolics Development, Sanofi-Aventis Deutschland 
      GmbH, Frankfurt, Germany.
FAU - Amano, Atsushi
AU  - Amano A
AD  - Research & Development, Sanofi K.K., Tokyo, Japan.
FAU - Hashimoto, Yasuhiro
AU  - Hashimoto Y
AD  - Research & Development, Sanofi K.K., Tokyo, Japan.
FAU - Niemoeller, Elisabeth
AU  - Niemoeller E
AD  - Diabetes, Cardiovascular and Metabolics Development, Sanofi-Aventis Deutschland 
      GmbH, Frankfurt, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT02749890
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200415
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Blood Glucose)
RN  - 0 (Drug Combinations)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Peptides)
RN  - 2ZM8CX04RZ (Insulin Glargine)
RN  - 74O62BB01U (lixisenatide)
SB  - IM
MH  - Administration, Oral
MH  - Aged
MH  - Blood Glucose/drug effects/metabolism
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Drug Combinations
MH  - Drug Resistance/drug effects
MH  - Female
MH  - Glycated Hemoglobin/drug effects/metabolism
MH  - Humans
MH  - Hypoglycemia/chemically induced
MH  - Hypoglycemic Agents/administration & dosage/adverse effects
MH  - Insulin Glargine/*administration & dosage/*adverse effects
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - Peptides/*administration & dosage/*adverse effects
PMC - PMC7245357
EDAT- 2020/04/17 06:00
MHDA- 2021/03/05 06:00
PMCR- 2020/04/15
CRDT- 2020/04/17 06:00
PHST- 2019/12/06 00:00 [received]
PHST- 2020/03/20 00:00 [accepted]
PHST- 2020/04/17 06:00 [pubmed]
PHST- 2021/03/05 06:00 [medline]
PHST- 2020/04/17 06:00 [entrez]
PHST- 2020/04/15 00:00 [pmc-release]
AID - dc19-2452 [pii]
AID - 2452 [pii]
AID - 10.2337/dc19-2452 [doi]
PST - ppublish
SO  - Diabetes Care. 2020 Jun;43(6):1249-1257. doi: 10.2337/dc19-2452. Epub 2020 Apr 
      15.