PMID- 36527386
OWN - NLM
STAT- MEDLINE
DCOM- 20230307
LR  - 20230321
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 25
IP  - 4
DP  - 2023 Apr
TI  - Phase I studies of the safety, tolerability, pharmacokinetics and 
      pharmacodynamics of the dual glucagon receptor/glucagon-like peptide-1 receptor 
      agonist BI 456906.
PG  - 1011-1023
LID - 10.1111/dom.14948 [doi]
AB  - AIM: To report two phase I studies of the novel subcutaneous glucagon-like 
      peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus 
      placebo in healthy volunteers and people with overweight/obesity. MATERIALS AND 
      METHODS: A phase Ia study (NCT03175211) investigated single rising doses (SRDs) 
      of BI 456906 in 24 males with a body mass index (BMI) of 20-<30 kg/m(2) . A phase 
      Ib study (NCT03591718) investigated multiple rising doses (MRDs) of BI 456906 
      (escalated over 6 [Part A] or 16 [Part B] weeks) in 125 adults with a BMI of 
      27-40 kg/m(2) . RESULTS: In the SRD study (N = 24), mean body weight decreased 
      with increasing BI 456906 dose. In the MRD study, the maximum decreases in 
      placebo-corrected mean body weight were at week 6 (-5.79%, dosage schedule [DS] 
      1; Part A) and week 16 (-13.8%, DS7; Part B). BI 456906 reduced plasma amino 
      acids and glucagon, indicating target engagement at GCGRs and GLP-1Rs. 
      Drug-related adverse events (AEs) increased with BI 456906 dose. The most 
      frequent drug-related AE with SRDs was decreased appetite (n = 9, 50.0%), and two 
      subjects (8.3%) did not complete the trial because of AEs (nausea and vomiting). 
      During MRD Part A (N = 80), 10 subjects (12.5%) discontinued BI 456906, most 
      commonly because of a cardiac or vascular AE (n = 6, 7.5%); during Part B 
      (N = 45), eight subjects (17.8%) discontinued BI 456906, mainly because of AEs 
      (n = 6, 13.3%), most commonly gastrointestinal disorders. CONCLUSIONS: BI 456906 
      produced a placebo-corrected body weight loss of 13.8% (week 16), highlighting 
      its potential to promote clinically meaningful body weight loss in people with 
      overweight/obesity.
CI  - (c) 2022 Boehringer Ingelheim and The Authors. Diabetes, Obesity and Metabolism 
      published by John Wiley & Sons Ltd.
FAU - Jungnik, Arvid
AU  - Jungnik A
AD  - Boehringer Ingelheim Pharma GmbH, Biberach, Germany.
FAU - Arrubla Martinez, Jorge
AU  - Arrubla Martinez J
AUID- ORCID: 0000-0002-5926-9472
AD  - Profil Institute for Metabolic Research, Neuss, Germany.
FAU - Plum-Morschel, Leona
AU  - Plum-Morschel L
AUID- ORCID: 0000-0002-1907-761X
AD  - Profil Mainz GmbH & Co. KG, Mainz, Germany.
FAU - Kapitza, Christoph
AU  - Kapitza C
AUID- ORCID: 0000-0002-9700-2373
AD  - Profil Institute for Metabolic Research, Neuss, Germany.
AD  - Profil Mainz GmbH & Co. KG, Mainz, Germany.
FAU - Lamers, Daniela
AU  - Lamers D
AD  - Profil Institute for Metabolic Research, Neuss, Germany.
FAU - Thamer, Claus
AU  - Thamer C
AD  - Boehringer Ingelheim Pharma GmbH, Biberach, Germany.
FAU - Scholch, Corinna
AU  - Scholch C
AD  - Boehringer Ingelheim Pharma GmbH, Biberach, Germany.
FAU - Desch, Michael
AU  - Desch M
AUID- ORCID: 0000-0003-0205-1592
AD  - Boehringer Ingelheim Pharma GmbH, Biberach, Germany.
FAU - Hennige, Anita M
AU  - Hennige AM
AD  - Boehringer Ingelheim International GmbH, Biberach, Germany.
LA  - eng
SI  - ClinicalTrials.gov/NCT03175211
SI  - ClinicalTrials.gov/NCT03591718
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230130
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Receptors, Glucagon)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Blood Glucose)
SB  - IM
MH  - Adult
MH  - Male
MH  - Humans
MH  - *Glucagon-Like Peptide 1/therapeutic use
MH  - Hypoglycemic Agents/therapeutic use
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Receptors, Glucagon/agonists
MH  - Glucagon-Like Peptide-1 Receptor/agonists
MH  - Overweight/drug therapy
MH  - Blood Glucose/metabolism
MH  - Body Weight
MH  - Obesity/drug therapy
MH  - Weight Loss
MH  - Double-Blind Method
OTO - NOTNLM
OT  - BI 456906
OT  - dual agonism
OT  - glucagon receptor agonist
OT  - glucagon-like peptide-1 receptor agonist
OT  - obesity
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - safety
OT  - tolerability
EDAT- 2022/12/18 06:00
MHDA- 2023/03/08 06:00
CRDT- 2022/12/17 08:22
PHST- 2022/11/21 00:00 [revised]
PHST- 2022/10/06 00:00 [received]
PHST- 2022/12/11 00:00 [accepted]
PHST- 2022/12/18 06:00 [pubmed]
PHST- 2023/03/08 06:00 [medline]
PHST- 2022/12/17 08:22 [entrez]
AID - 10.1111/dom.14948 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2023 Apr;25(4):1011-1023. doi: 10.1111/dom.14948. Epub 2023 
      Jan 30.