PMID- 31175319
OWN - NLM
STAT- MEDLINE
DCOM- 20210226
LR  - 20210731
IS  - 1476-5497 (Electronic)
IS  - 0307-0565 (Print)
IS  - 0307-0565 (Linking)
VI  - 44
IP  - 2
DP  - 2020 Feb
TI  - Long-acting CCK analogue NN9056 lowers food intake and body weight in obese 
      Gottingen Minipigs.
PG  - 447-456
LID - 10.1038/s41366-019-0386-0 [doi]
AB  - BACKGROUND/OBJECTIVES: Cholecystokinin (CCK) is a regulator of appetite and 
      energy intake in man. The aim of this study was to determine the effect of 
      NN9056, a long-acting CCK-1 receptor-selective CCK analogue, on food intake and 
      body weight (BW) in obese Gottingen Minipigs. SUBJECTS/METHODS: Tolerability of 
      NN9056 and acute effects on food intake, pancreas histology, amylase and lipase 
      levels were assessed in lean domestic pigs in doses up to 100 nmol/kg (n = 3-4). 
      Subsequently, obese Gottingen Minipigs were treated subcutaneously (s.c.) once 
      daily for 13 weeks with vehicle, NN9056 low dose (regulated from 5 to 2 nmol/kg) 
      or NN9056 high dose (10 nmol/kg) (n = 7-8). Food intake was measured daily and BW 
      twice weekly. At the end of the treatment period, an intravenous glucose 
      tolerance test (IVGTT) and a 24-h exposure profile was obtained. Data are 
      mean +/- SD. RESULTS: The acute studies in domestic pigs showed significant and 
      dose-dependent effect of NN9056 on food intake, acceptable tolerability and no 
      histopathological signs of pancreatitis. Sub-chronic treatment in obese Gottingen 
      Minipigs was also well tolerated and accumulated food intake was significantly 
      lower in both treated groups compared to vehicle, with no significant difference 
      between the dose levels of NN9056 (41.8 +/- 12.6, 51.5 +/- 13.8 and 86.5 +/- 19.5 kg in 
      high-dose, low-dose and vehicle groups, respectively, p = 0.012 and p < 0.0001 
      for low and high dose vs. vehicle, respectively). Accordingly, there was a weight 
      loss in both treated groups vs. a weight gain in the vehicle group (-7.2 +/- 4.6%, 
      -2.3 +/- 3.2% and 12.3 +/- 3.9% in the high-dose, low-dose and vehicle groups, 
      respectively, p < 0.0001 for both vs. vehicle). IVGTT data were not significantly 
      different between groups. CONCLUSION: NN9056, a long-acting CCK-1 
      receptor-selective CCK analogue, significantly reduced food intake and BW in 
      obese Gottingen Minipigs after once daily s.c. dosing for 13 weeks.
FAU - Christoffersen, Berit O
AU  - Christoffersen BO
AD  - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, 2760, Malov, Denmark.
FAU - Skyggebjerg, Rikke Bjerring
AU  - Skyggebjerg RB
AD  - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, 2760, Malov, Denmark.
FAU - Bugge, Anne
AU  - Bugge A
AD  - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, 2760, Malov, Denmark.
FAU - Kirk, Rikke Kaae
AU  - Kirk RK
AD  - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, 2760, Malov, Denmark.
FAU - Vestergaard, Bill
AU  - Vestergaard B
AD  - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, 2760, Malov, Denmark.
FAU - Uldam, Henriette Kold
AU  - Uldam HK
AD  - Global Research Technologies, Novo Nordisk A/S, Novo Nordisk Park, 2760, Malov, 
      Denmark.
FAU - Fels, Johannes Josef
AU  - Fels JJ
AUID- ORCID: 0000-0002-6616-6746
AD  - Global Research Technologies, Novo Nordisk A/S, Novo Nordisk Park, 2760, Malov, 
      Denmark.
FAU - Pyke, Charles
AU  - Pyke C
AD  - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, 2760, Malov, Denmark.
FAU - Sensfuss, Ulrich
AU  - Sensfuss U
AD  - Global Research Technologies, Novo Nordisk A/S, Novo Nordisk Park, 2760, Malov, 
      Denmark.
FAU - Sanfridson, Annika
AU  - Sanfridson A
AD  - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, 2760, Malov, Denmark.
FAU - Clausen, Trine Ryberg
AU  - Clausen TR
AD  - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, 2760, Malov, Denmark. 
      TRRS@novonordisk.com.
LA  - eng
PT  - Journal Article
DEP - 20190607
PL  - England
TA  - Int J Obes (Lond)
JT  - International journal of obesity (2005)
JID - 101256108
RN  - 9011-97-6 (Cholecystokinin)
SB  - IM
MH  - Animals
MH  - Body Weight/*drug effects
MH  - *Cholecystokinin/adverse effects/analogs & derivatives/metabolism/pharmacology
MH  - Disease Models, Animal
MH  - Eating/*drug effects
MH  - Energy Intake/*drug effects
MH  - Female
MH  - Humans
MH  - Obesity/*metabolism
MH  - Protein Binding
MH  - Swine
MH  - Swine, Miniature
PMC - PMC6997118
COIS- All authors are or were employees at Novo Nordisk A/S when the work was done, and 
      most are minor shareholders in Novo Nordisk A/S.
EDAT- 2019/06/09 06:00
MHDA- 2021/02/27 06:00
PMCR- 2019/06/07
CRDT- 2019/06/09 06:00
PHST- 2018/11/03 00:00 [received]
PHST- 2019/04/05 00:00 [accepted]
PHST- 2019/03/16 00:00 [revised]
PHST- 2019/06/09 06:00 [pubmed]
PHST- 2021/02/27 06:00 [medline]
PHST- 2019/06/09 06:00 [entrez]
PHST- 2019/06/07 00:00 [pmc-release]
AID - 10.1038/s41366-019-0386-0 [pii]
AID - 386 [pii]
AID - 10.1038/s41366-019-0386-0 [doi]
PST - ppublish
SO  - Int J Obes (Lond). 2020 Feb;44(2):447-456. doi: 10.1038/s41366-019-0386-0. Epub 
      2019 Jun 7.