PMID- 26358288
OWN - NLM
STAT- MEDLINE
DCOM- 20160726
LR  - 20221207
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Linking)
VI  - 39
IP  - 2
DP  - 2016 Feb
TI  - A Phase 2, Randomized, Dose-Finding Study of the Novel Once-Weekly Human GLP-1 
      Analog, Semaglutide, Compared With Placebo and Open-Label Liraglutide in Patients 
      With Type 2 Diabetes.
PG  - 231-41
LID - 10.2337/dc15-0165 [doi]
AB  - OBJECTIVE: To investigate the dose-response relationship of semaglutide versus 
      placebo and open-label liraglutide in terms of glycemic control in patients with 
      type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a 12-week, randomized, 
      double-blind phase 2 trial. Patients (n = 415) were randomized to receive a 
      subcutaneous injection of semaglutide once weekly without dose escalation 
      (0.1-0.8 mg) or with dose escalation (E) (0.4 mg steps to 0.8 or 1.6 mg E over 
      1-2 weeks), open-label liraglutide once daily (1.2 or 1.8 mg), or placebo. The 
      primary end point was change in HbA1c level from baseline. Secondary end points 
      included change in body weight, safety, and tolerability. RESULTS: Semaglutide 
      dose-dependently reduced the level of HbA1c from baseline (8.1 +/- 0.8%) to week 12 
      by up to -1.7%, and body weight by up to -4.8 kg (1.6 mg E, P < 0.001 vs. 
      placebo). Up to 81% of patients achieved an HbA1c level of <7%. HbA1c level and 
      weight reductions with semaglutide 1.6 mg E were greater than those with 
      liraglutide 1.2 and 1.8 mg (based on unadjusted CIs), but adverse events (AEs) 
      and withdrawals occurred more frequently. The incidence of nausea, vomiting, and 
      withdrawal due to gastrointestinal AEs increased with the semaglutide dose; most 
      events were mild to moderate, transient, and ameliorated by dose escalation. 
      There were no major episodes of hypoglycemia and few cases of injection site 
      reactions. CONCLUSIONS: After 12 weeks, semaglutide dose-dependently reduced 
      HbA1c level and weight in patients with type 2 diabetes. No unexpected safety or 
      tolerability concerns were identified; gastrointestinal AEs typical of 
      glucagon-like peptide 1 receptor agonists were mitigated by dose escalation. On 
      this basis, weekly semaglutide doses of 0.5 and 1.0 mg with a 4-week dose 
      escalation were selected for phase 3.
CI  - (c) 2016 by the American Diabetes Association. Readers may use this article as long 
      as the work is properly cited, the use is educational and not for profit, and the 
      work is not altered.
FAU - Nauck, Michael A
AU  - Nauck MA
AD  - Diabetes Centre, Bad Lauterberg, Harz, Germany michael.nauck@rub.de.
FAU - Petrie, John R
AU  - Petrie JR
AD  - University of Glasgow, Glasgow, U.K.
FAU - Sesti, Giorgio
AU  - Sesti G
AD  - University Magna Graecia, Catanzaro, Italy.
FAU - Mannucci, Edoardo
AU  - Mannucci E
AD  - Careggi Teaching Hospital, Florence, Italy.
FAU - Courreges, Jean-Pierre
AU  - Courreges JP
AD  - General Hospital, Narbonne, France.
FAU - Lindegaard, Marie L
AU  - Lindegaard ML
AD  - Novo Nordisk A/S, Soborg, Denmark.
FAU - Jensen, Christine B
AU  - Jensen CB
AD  - Novo Nordisk A/S, Soborg, Denmark.
FAU - Atkin, Stephen L
AU  - Atkin SL
AD  - Weill Cornell Medical College Qatar, Doha, Qatar.
CN  - Study 1821 Investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT00696657
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150910
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 53AXN4NNHX (semaglutide)
RN  - 62340-29-8 (Glucagon-Like Peptides)
RN  - 839I73S42A (Liraglutide)
SB  - IM
MH  - Adult
MH  - Blood Glucose/drug effects
MH  - Body Weight
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Glucagon-Like Peptides/*administration & dosage/adverse effects/analogs & 
      derivatives
MH  - Glycated Hemoglobin/analysis/drug effects
MH  - Humans
MH  - Hypoglycemia/chemically induced
MH  - Hypoglycemic Agents/*administration & dosage/adverse effects
MH  - Injections, Subcutaneous
MH  - Liraglutide/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Nausea/chemically induced
MH  - Treatment Outcome
MH  - Vomiting/chemically induced
EDAT- 2015/09/12 06:00
MHDA- 2016/07/28 06:00
CRDT- 2015/09/12 06:00
PHST- 2015/01/23 00:00 [received]
PHST- 2015/08/04 00:00 [accepted]
PHST- 2015/09/12 06:00 [entrez]
PHST- 2015/09/12 06:00 [pubmed]
PHST- 2016/07/28 06:00 [medline]
AID - dc15-0165 [pii]
AID - 10.2337/dc15-0165 [doi]
PST - ppublish
SO  - Diabetes Care. 2016 Feb;39(2):231-41. doi: 10.2337/dc15-0165. Epub 2015 Sep 10.