PMID- 28283565
OWN - NLM
STAT- MEDLINE
DCOM- 20170824
LR  - 20181202
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Linking)
VI  - 40
IP  - 5
DP  - 2017 May
TI  - Assessment of Pancreas Safety in the Development Program of Once-Weekly GLP-1 
      Receptor Agonist Dulaglutide.
PG  - 647-654
LID - 10.2337/dc16-0984 [doi]
AB  - OBJECTIVE: To assess the risk of acute pancreatitis during treatment with 
      glucagon-like peptide 1 receptor agonist dulaglutide, placebo, and active 
      comparators across phase 2/3 dulaglutide trials. RESEARCH DESIGN AND METHODS: A 
      total of 6,005 patients with type 2 diabetes participated (dulaglutide group N = 
      4,006 [dose range 0.1-3.0 mg]; active comparator group [metformin, sitagliptin, 
      exenatide twice daily, insulin glargine] N = 1,541; placebo group N = 703; 245 
      placebo-treated patients subsequently received dulaglutide or sitagliptin and 
      were also included in these groups) for up to 104 weeks. The following events 
      were adjudicated: investigator-reported pancreatitis, adverse events (AEs) of 
      severe or serious abdominal pain of unknown etiology, and confirmed asymptomatic 
      increases in pancreatic enzymes >/=3x the upper limit of normal range. RESULTS: 
      Overall, 203 events from 151 patients underwent adjudication (dulaglutide group n 
      = 108; comparator group including placebo n = 43). Acute pancreatitis was 
      confirmed by adjudication in seven patients (dulaglutide n = 3, placebo n = 1, 
      sitagliptin n = 3). Exposure-adjusted incidence rates were as follows: 
      dulaglutide group 0.85 patients/1,000 patient-years, placebo group 3.52 
      patients/1,000 patient-years, sitagliptin group 4.71 patients/1,000 
      patient-years. No events of pancreatitis were confirmed by adjudication in 
      patients treated with exenatide twice daily, metformin, or glargine. Increases in 
      median values of lipase and pancreatic amylase within the normal range were 
      observed with all treatments except glargine. These changes were not associated 
      with AEs. CONCLUSIONS: The exposure-adjusted incidence rate of acute pancreatitis 
      in dulaglutide-treated patients was similar to the rates with placebo, with few 
      reported cases during the entire program.
CI  - (c) 2017 by the American Diabetes Association.
FAU - Nauck, Michael A
AU  - Nauck MA
AUID- ORCID: 0000-0003-2455-0472
AD  - Division of Diabetology, Medical Department I, St. Josef-Hospital 
      (Ruhr-Universitat Bochum), Bochum, Germany.
FAU - Frossard, Jean-Louis
AU  - Frossard JL
AUID- ORCID: 0000-0002-6309-1603
AD  - Division of Gastroenterology, University Hospital of Geneva, Geneva, Switzerland.
FAU - Barkin, Jamie S
AU  - Barkin JS
AUID- ORCID: 0000-0001-5109-9053
AD  - Division of Gastroenterology, Department of Medicine, University of Miami Leonard 
      M. Miller School of Medicine, Miami, FL.
FAU - Anglin, Greg
AU  - Anglin G
AD  - Eli Lilly Canada, Toronto, Ontario, Canada.
FAU - Hensley, Ingrid E
AU  - Hensley IE
AD  - Eli Lilly and Company, Indianapolis, IN.
FAU - Harper, Kristine D
AU  - Harper KD
AUID- ORCID: 0000-0001-8490-7520
AD  - Eli Lilly and Company, Indianapolis, IN.
FAU - Milicevic, Zvonko
AU  - Milicevic Z
AUID- ORCID: 0000-0002-6746-901X
AD  - Eli Lilly and Company, Vienna, Austria milicevic_zvonko@lilly.com.
LA  - eng
PT  - Journal Article
DEP - 20170310
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Peptides)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Venoms)
RN  - 2ZM8CX04RZ (Insulin Glargine)
RN  - 62340-29-8 (Glucagon-Like Peptides)
RN  - 9100L32L2N (Metformin)
RN  - 9P1872D4OL (Exenatide)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
RN  - WTT295HSY5 (dulaglutide)
SB  - IM
MH  - Acute Disease
MH  - Diabetes Mellitus, Type 2/drug therapy
MH  - Exenatide
MH  - Female
MH  - Glucagon-Like Peptide-1 Receptor/*agonists
MH  - Glucagon-Like Peptides/adverse effects/*analogs & derivatives/therapeutic use
MH  - Humans
MH  - Hypoglycemic Agents/*adverse effects/*therapeutic use
MH  - Immunoglobulin Fc Fragments/*adverse effects/*therapeutic use
MH  - Insulin Glargine/adverse effects/therapeutic use
MH  - Male
MH  - Metformin/adverse effects/therapeutic use
MH  - Middle Aged
MH  - Pancreatitis/*chemically induced
MH  - Peptides/adverse effects/therapeutic use
MH  - Recombinant Fusion Proteins/*adverse effects/*therapeutic use
MH  - Sitagliptin Phosphate/adverse effects/therapeutic use
MH  - Venoms/adverse effects/therapeutic use
EDAT- 2017/03/12 06:00
MHDA- 2017/08/25 06:00
CRDT- 2017/03/12 06:00
PHST- 2016/05/05 00:00 [received]
PHST- 2017/02/05 00:00 [accepted]
PHST- 2017/03/12 06:00 [pubmed]
PHST- 2017/08/25 06:00 [medline]
PHST- 2017/03/12 06:00 [entrez]
AID - dc16-0984 [pii]
AID - 10.2337/dc16-0984 [doi]
PST - ppublish
SO  - Diabetes Care. 2017 May;40(5):647-654. doi: 10.2337/dc16-0984. Epub 2017 Mar 10.