PMID- 32910487
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20240329
IS  - 1365-2710 (Electronic)
IS  - 0269-4727 (Print)
IS  - 0269-4727 (Linking)
VI  - 45 Suppl 1
IP  - Suppl 1
DP  - 2020 Sep
TI  - Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 
      diabetes.
PG  - 43-60
LID - 10.1111/jcpt.13225 [doi]
AB  - WHAT IS KNOWN AND OBJECTIVE: In recent years, glucagon-like peptide-1 receptor 
      agonists (GLP-1 RAs) including once-weekly (QW) formulations have been 
      incorporated into type 2 diabetes (T2D) clinical guidelines, making it essential 
      that pharmacists and healthcare professionals (HCPs) have a clear understanding 
      of their safety profiles. Currently, three QW GLP-1 RAs are approved and marketed 
      in the United States for the treatment of T2D: dulaglutide, exenatide 
      extended-release and semaglutide. This review provides pharmacists and HCPs with 
      collated data related to potential safety and tolerability issues when patients 
      use QW GLP-1 RAs, enabling patient education and treatment optimization. METHODS: 
      This is a narrative review comparing the safety and tolerability of the three QW 
      GLP-1 RAs, using data from Phase 3 clinical trials. Extracted safety data 
      included gastrointestinal (GI) adverse events (AEs), hypoglycaemia, 
      injection-site reactions, pancreatitis, neoplasms, gallbladder events, and 
      diabetic retinopathy (DR) and/or its complications (DRCs). RESULTS AND 
      DISCUSSION: A total of 30 trials were identified for inclusion; eight were 
      head-to-head trials involving another GLP-1 RA; of these, six compared GLP-1 RAs 
      with different dosing regimens (QW vs once-daily or twice-daily), and two were 
      direct QW vs QW GLP-1 RA comparisons. The most commonly reported AEs were GI 
      events (notably nausea, vomiting and diarrhoea), but there was variation between 
      the three QW drugs. These were generally mild-to-moderate in severity and 
      transient. Risk of hypoglycaemia, injection-site reactions, pancreatitis, 
      neoplasms and gallbladder events was generally low across the GLP-1 RAs 
      investigated. Overall rates of DR or DRC were low across the trials. Only in one 
      trial (SUSTAIN 6) there were significantly more DRC events reported in patients 
      treated with QW semaglutide (3.0%) compared with placebo (1.8%). This was likely 
      due to the rapid improvement in glucose control in patients with pre-existing DR 
      enrolled within that trial. WHAT IS NEW AND CONCLUSION: This review puts the 
      latest clinical data from the marketed QW GLP-1 RAs into context with results 
      from older Phase 3 trials, to enable pharmacists and HCPs to make informed 
      treatment decisions. Each of the three QW GLP-1 RAs has their own safety profile, 
      which should be considered when choosing the optimal treatment for patients.
CI  - (c) 2020 The Authors. Journal of Clinical Pharmacy and Therapeutics published by 
      John Wiley & Sons Ltd.
FAU - Trujillo, Jennifer
AU  - Trujillo J
AUID- ORCID: 0000-0001-7898-8029
AD  - Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical 
      Sciences, University of Colorado, Aurora, CO, USA.
LA  - eng
GR  - Novo Nordisk Inc./
PT  - Journal Article
PT  - Review
PL  - England
TA  - J Clin Pharm Ther
JT  - Journal of clinical pharmacy and therapeutics
JID - 8704308
RN  - 0 (Blood Glucose)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 53AXN4NNHX (semaglutide)
RN  - 62340-29-8 (Glucagon-Like Peptides)
RN  - 9P1872D4OL (Exenatide)
RN  - WTT295HSY5 (dulaglutide)
SB  - IM
MH  - Blood Glucose/drug effects
MH  - Delayed-Action Preparations
MH  - Diabetes Mellitus, Type 2/*drug therapy/physiopathology
MH  - Drug Administration Schedule
MH  - Exenatide/administration & dosage/adverse effects/pharmacology
MH  - Glucagon-Like Peptide-1 Receptor/*agonists/metabolism
MH  - Glucagon-Like Peptides/administration & dosage/adverse effects/analogs & 
      derivatives/pharmacology
MH  - Humans
MH  - Hypoglycemic Agents/*administration & dosage/adverse effects/pharmacology
MH  - Immunoglobulin Fc Fragments/administration & dosage/adverse effects/pharmacology
MH  - Recombinant Fusion Proteins/administration & dosage/adverse effects/pharmacology
PMC - PMC7540535
OTO - NOTNLM
OT  - GLP-1 RA
OT  - dulaglutide
OT  - exenatide
OT  - safety
OT  - semaglutide
OT  - tolerability
OT  - type 2 diabetes
COIS- J Trujillo has acted as a consultant and advisory board member for Novo Nordisk, 
      Sanofi and BD Pharmaceuticals.
EDAT- 2020/09/11 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/10/07
CRDT- 2020/09/10 12:28
PHST- 2020/02/05 00:00 [received]
PHST- 2020/04/30 00:00 [revised]
PHST- 2020/05/13 00:00 [accepted]
PHST- 2020/09/10 12:28 [entrez]
PHST- 2020/09/11 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/10/07 00:00 [pmc-release]
AID - JCPT13225 [pii]
AID - 10.1111/jcpt.13225 [doi]
PST - ppublish
SO  - J Clin Pharm Ther. 2020 Sep;45 Suppl 1(Suppl 1):43-60. doi: 10.1111/jcpt.13225.