PMID- 28730694
OWN - NLM
STAT- MEDLINE
DCOM- 20180712
LR  - 20220410
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 19
IP  - 10
DP  - 2017 Oct
TI  - Pharmacodynamics, pharmacokinetics and safety of multiple ascending doses of the 
      novel dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 
      agonist RG7697 in people with type 2 diabetes mellitus.
PG  - 1436-1445
LID - 10.1111/dom.13024 [doi]
AB  - AIMS: To investigate the pharmacodynamics, pharmacokinetics and safety of 
      multiple ascending doses of RG7697, a dual glucose-dependent insulinotropic 
      polypeptide/glucagon-like peptide-1 agonist, in patients with type 2 diabetes 
      mellitus (T2D). METHODS: A total of 56 patients with T2D received once-daily 
      subcutaneous (s.c.) injection of RG7697 (0.25-2.5 mg) or placebo for 14 days in a 
      randomized, double-blind, dose-escalation study. Adverse events (AEs), vital 
      signs, ECGs and routine laboratory variables were intensively monitored. Drug 
      concentrations, fasting glycaemic variables, 24-hour glucose profiles, glycated 
      haemoglobin (HbA1c) and antibody formation were measured. Several meal tolerance 
      and gastric emptying tests were performed during the study. RESULTS: Daily s.c. 
      injections of RG7697 were well tolerated by the majority of participants with 
      T2D. The most frequently reported AEs with RG7697 were diarrhoea, nausea and 
      decreased appetite. Asymptomatic events of hypoglycaemia were relatively 
      uniformly distributed across dose groups including placebo. Pharmacokinetic 
      steady-state was achieved within 1 week. Meaningful reductions in fasting, 
      postprandial and 24-hour plasma glucose profile were observed at doses >/=0.75 mg, 
      and were associated with numerical decreases in HbA1c (-0.67% [2.5-mg dose] vs 
      -0.21% [placebo]). Decrease in postprandial insulin at doses >/=1.1 mg suggested 
      improvement in insulin sensitivity. Minimum delay in gastric emptying and body 
      weight reductions numerically greater than placebo (- 3.0 kg vs -0.9 kg) were 
      seen at the highest dose of 2.5 mg. CONCLUSIONS: Daily doses of RG7697 for 
      2 weeks were well tolerated by the majority of patients with T2D. Pharmacokinetic 
      data supported once-daily dosing and pharmacodynamic effect displayed 
      dose-dependent reductions in fasting and postprandial plasma glucose, without 
      increasing the risk of hypoglycaemia.
CI  - (c) 2017 John Wiley & Sons Ltd.
FAU - Schmitt, Christophe
AU  - Schmitt C
AUID- ORCID: 0000-0001-8001-5584
AD  - Department of Clinical Pharmacology, F. Hoffmann-La Roche AG, Basel, Switzerland.
FAU - Portron, Agnes
AU  - Portron A
AD  - Department of Clinical Pharmacology, F. Hoffmann-La Roche AG, Basel, Switzerland.
FAU - Jadidi, Shirin
AU  - Jadidi S
AD  - Department of Safety Science, Roche Innovation Center, New York, New York.
FAU - Sarkar, Neena
AU  - Sarkar N
AD  - Department of Biostatistics, Roche Innovation Center, New York, New York.
FAU - DiMarchi, Richard
AU  - DiMarchi R
AD  - Department of Chemistry, Novo Nordisk Research Center Indianapolis, Indianapolis, 
      Indiana.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170720
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Blood Glucose)
RN  - 0 (Drugs, Investigational)
RN  - 0 (Hypoglycemic Agents)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Blood Glucose/drug effects/metabolism
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drugs, Investigational/administration & dosage/pharmacokinetics
MH  - Female
MH  - Gastric Inhibitory Polypeptide/agonists
MH  - Glucagon-Like Peptide 1/agonists
MH  - Humans
MH  - Hypoglycemic Agents/*administration & dosage/*pharmacokinetics
MH  - Male
MH  - Middle Aged
OTO - NOTNLM
OT  - NNC0090-2746
OT  - RG7697, RO6811135
OT  - dual GIP/GLP-1 agonist
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - safety
OT  - type 2 diabetes mellitus
EDAT- 2017/07/22 06:00
MHDA- 2018/07/13 06:00
CRDT- 2017/07/22 06:00
PHST- 2017/02/26 00:00 [received]
PHST- 2017/05/19 00:00 [revised]
PHST- 2017/05/29 00:00 [accepted]
PHST- 2017/07/22 06:00 [pubmed]
PHST- 2018/07/13 06:00 [medline]
PHST- 2017/07/22 06:00 [entrez]
AID - 10.1111/dom.13024 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2017 Oct;19(10):1436-1445. doi: 10.1111/dom.13024. Epub 2017 
      Jul 20.