PMID- 34127852
OWN - NLM
STAT- MEDLINE
DCOM- 20210819
LR  - 20211005
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Linking)
VI  - 27
IP  - 6
DP  - 2021 Jun
TI  - Danuglipron (PF-06882961) in type 2 diabetes: a randomized, placebo-controlled, 
      multiple ascending-dose phase 1 trial.
PG  - 1079-1087
LID - 10.1038/s41591-021-01391-w [doi]
AB  - Agonism of the glucagon-like peptide-1 receptor (GLP-1R) results in glycemic 
      lowering and body weight loss and is a therapeutic strategy to treat type 2 
      diabetes (T2D) and obesity. We developed danuglipron (PF-06882961), an oral 
      small-molecule GLP-1R agonist and found it had comparable efficacy to injectable 
      peptidic GLP-1R agonists in a humanized mouse model. We then completed a 
      placebo-controlled, randomized, double-blind, multiple ascending-dose phase 1 
      study ( NCT03538743 ), in which we enrolled 98 patients with T2D on background 
      metformin and randomized them to receive multiple ascending doses of danuglipron 
      or placebo for 28 d, across eight cohorts. The primary outcomes were assessment 
      of adverse events (AEs), safety laboratory tests, vital signs and 12-lead 
      electrocardiograms. Most AEs were mild, with nausea, dyspepsia and vomiting most 
      commonly reported. There were no clinically meaningful AEs in laboratory values 
      across groups. Heart rate generally increased with danuglipron treatment at day 
      28, but no heart-rate AEs were reported. Systolic blood pressure was slightly 
      decreased and changes in diastolic blood pressure were similar with danuglipron 
      treatment at day 28, compared with placebo. There were no clinically meaningful 
      electrocardiogram findings. In this study in T2D, danuglipron was generally well 
      tolerated, with a safety profile consistent with the mechanism of action of 
      GLP-1R agonism.
FAU - Saxena, Aditi R
AU  - Saxena AR
AUID- ORCID: 0000-0001-6017-1838
AD  - Pfizer Worldwide Research and Development, Cambridge, MA, USA. 
      aditi.saxena@pfizer.com.
FAU - Gorman, Donal N
AU  - Gorman DN
AUID- ORCID: 0000-0003-4853-9817
AD  - Pfizer Worldwide Research and Development, Cambridge, UK.
FAU - Esquejo, Ryan M
AU  - Esquejo RM
AD  - Pfizer Worldwide Research and Development, Cambridge, MA, USA.
FAU - Bergman, Arthur
AU  - Bergman A
AD  - Pfizer Worldwide Research and Development, Cambridge, MA, USA.
FAU - Chidsey, Kristin
AU  - Chidsey K
AD  - Pfizer Worldwide Research and Development, Cambridge, MA, USA.
FAU - Buckeridge, Clare
AU  - Buckeridge C
AD  - Pfizer Worldwide Research and Development, Cambridge, MA, USA.
FAU - Griffith, David A
AU  - Griffith DA
AUID- ORCID: 0000-0002-7592-2478
AD  - Pfizer Worldwide Research and Development, Cambridge, MA, USA.
FAU - Kim, Albert M
AU  - Kim AM
AUID- ORCID: 0000-0002-5269-2155
AD  - Pfizer Worldwide Research and Development, Cambridge, MA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03538743
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210614
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Blood Glucose)
RN  - 0 (GLP1R protein, human)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 9100L32L2N (Metformin)
SB  - IM
CIN - Nat Med. 2021 Jun;27(6):952-953. PMID: 34127851
MH  - Animals
MH  - Blood Glucose/drug effects
MH  - Body Weight/drug effects
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy/genetics/pathology
MH  - Female
MH  - Glucagon-Like Peptide-1 Receptor/agonists/*genetics
MH  - Humans
MH  - Hypoglycemic Agents/*administration & dosage/adverse effects
MH  - Male
MH  - Metformin/administration & dosage
MH  - Mice
MH  - Middle Aged
MH  - Obesity/blood/*drug therapy/genetics/pathology
EDAT- 2021/06/16 06:00
MHDA- 2021/08/20 06:00
CRDT- 2021/06/15 06:49
PHST- 2020/10/16 00:00 [received]
PHST- 2021/05/10 00:00 [accepted]
PHST- 2021/06/16 06:00 [pubmed]
PHST- 2021/08/20 06:00 [medline]
PHST- 2021/06/15 06:49 [entrez]
AID - 10.1038/s41591-021-01391-w [pii]
AID - 10.1038/s41591-021-01391-w [doi]
PST - ppublish
SO  - Nat Med. 2021 Jun;27(6):1079-1087. doi: 10.1038/s41591-021-01391-w. Epub 2021 Jun 
      14.