PMID- 37852529
OWN - NLM
STAT- MEDLINE
DCOM- 20231121
LR  - 20231129
IS  - 1532-8600 (Electronic)
IS  - 0026-0495 (Linking)
VI  - 149
DP  - 2023 Dec
TI  - Safety and efficacy of the new, oral, small-molecule, GLP-1 receptor agonists 
      orforglipron and danuglipron for the treatment of type 2 diabetes and obesity: 
      systematic review and meta-analysis of randomized controlled trials.
PG  - 155710
LID - S0026-0495(23)00314-1 [pii]
LID - 10.1016/j.metabol.2023.155710 [doi]
AB  - AIMS: The present systematic review aimed to synthesize available data from 
      recently published randomized trials (RCTs) investigating the efficacy and safety 
      of the novel, orally administered, small-molecule glucagon-like peptide 1 
      receptor agonists (GLP-1RAs) orforglipron and danuglipron for the treatment of 
      type 2 diabetes mellitus (T2DM), obesity or both. METHODS: Literature search was 
      performed through Medline (via PubMed), Cochrane Library and Scopus until August 
      16, 2023. Double-independent study selection, data extraction and quality 
      assessment were performed. Evidence was pooled with random effects meta-analysis. 
      RESULTS: Totally, 1037 patients among seven RCTs were analyzed. All RCTs had low 
      risk of bias according to the Cochrane Collaboration tool (RoB2). Novel GLP-1RAs 
      led to significant reduction in HbA1c in patients with T2DM compared to controls 
      (MD = -1.03 %; 95 % CI = [-1.29, -0.77]; P < 0.001). A significantly greater 
      weight reduction was also noted both in patients with T2DM or obesity compared to 
      controls (MD = -3.26 kg; 95 % CI = [-4.79, -1.72]; P < 0.001 and MD = -7.52 kg; 
      95 % CI = [-14.63, -0.41]; P = 0.038, respectively; P for subgroup 
      differences = 0.25). Regarding safety, novel GLP-1RAs showed a neutral effect on 
      the odds of severe hypoglycemia or serious adverse events (OR = 0.34; 95 % 
      CI = [0.09, 1.31]; P = 0.11 and OR = 0.95; 95 % CI = [0.39, 2.34]; P = 0.91, 
      respectively) and significantly higher odds of gastrointestinal, 
      treatment-emergent adverse events (OR = 2.57; 95 % CI = [1.49, 4.42]; P < 0.001) 
      and adverse events leading to discontinuation (OR = 2.89; 95 % CI = [1.22, 6.87]; 
      P = 0.016). CONCLUSION: Preliminary evidence supports that orforglipron and 
      danuglipron are efficient in glycemic control and weight reduction in T2DM, 
      obesity or both. More longitudinal research is warranted in order to provide 
      deeper insights into their efficacy, safety and tolerability before their 
      potential incorporation in the pharmacological arsenal against T2DM or obesity.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Karakasis, Paschalis
AU  - Karakasis P
AD  - Second Department of Cardiology, Aristotle University of Thessaloniki, General 
      Hospital "Hippokration", Greece. Electronic address: pakar15@hotmail.com.
FAU - Patoulias, Dimitrios
AU  - Patoulias D
AD  - Outpatient Department of Cardiometabolic Medicine, Aristotle University of 
      Thessaloniki, General Hospital "Hippokration", Greece; Second Department of 
      Internal Medicine, European Interbalkan Medical Center, Thessaloniki, Greece.
FAU - Pamporis, Konstantinos
AU  - Pamporis K
AD  - Department of Hygiene, Social-Preventive Medicine & Medical Statistics, Medical 
      School, Aristotle University of Thessaloniki, University Campus, Thessaloniki, 
      Greece.
FAU - Stachteas, Panagiotis
AU  - Stachteas P
AD  - Second Department of Cardiology, Aristotle University of Thessaloniki, General 
      Hospital "Hippokration", Greece.
FAU - Bougioukas, Konstantinos I
AU  - Bougioukas KI
AD  - Department of Hygiene, Social-Preventive Medicine & Medical Statistics, Medical 
      School, Aristotle University of Thessaloniki, University Campus, Thessaloniki, 
      Greece.
FAU - Klisic, Aleksandra
AU  - Klisic A
AD  - Primary Health Care Center, Faculty of Medicine, University of Montenegro, 
      Podgorica, Montenegro.
FAU - Fragakis, Nikolaos
AU  - Fragakis N
AD  - Second Department of Cardiology, Aristotle University of Thessaloniki, General 
      Hospital "Hippokration", Greece.
FAU - Rizzo, Manfredi
AU  - Rizzo M
AD  - Department of Health Promotion, Mother and Child Care, Internal Medicine and 
      Medical Specialties, School of Medicine, University of Palermo, Italy.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20231016
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
SB  - IM
MH  - Humans
MH  - *Glucagon-Like Peptide-1 Receptor
MH  - Randomized Controlled Trials as Topic
MH  - Hypoglycemic Agents/adverse effects
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Obesity/drug therapy
MH  - Weight Loss
OTO - NOTNLM
OT  - Danuglipron
OT  - GLP-1RAs
OT  - Obesity
OT  - Orforglipron
OT  - Type 2 diabetes mellitus
COIS- Declaration of competing interest None declared.
EDAT- 2023/10/19 00:44
MHDA- 2023/11/21 06:42
CRDT- 2023/10/18 19:28
PHST- 2023/08/23 00:00 [received]
PHST- 2023/10/15 00:00 [revised]
PHST- 2023/10/15 00:00 [accepted]
PHST- 2023/11/21 06:42 [medline]
PHST- 2023/10/19 00:44 [pubmed]
PHST- 2023/10/18 19:28 [entrez]
AID - S0026-0495(23)00314-1 [pii]
AID - 10.1016/j.metabol.2023.155710 [doi]
PST - ppublish
SO  - Metabolism. 2023 Dec;149:155710. doi: 10.1016/j.metabol.2023.155710. Epub 2023 
      Oct 16.