PMID- 36800286
OWN - NLM
STAT- MEDLINE
DCOM- 20230619
LR  - 20240202
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 108
IP  - 7
DP  - 2023 Jun 16
TI  - GLP-1 Receptor Agonists and Risk of Adverse Cerebrovascular Outcomes in Type 2 
      Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
PG  - 1806-1812
LID - 10.1210/clinem/dgad076 [doi]
AB  - CONTEXT: The effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on 
      ischemic/hemorrhagic stroke and transient ischemic attacks (TIA) in type 2 
      diabetes mellitus (T2DM) remains undetermined. OBJECTIVE: To pool effects of 
      GLP-1RAs on adverse cerebrovascular outcomes and investigate impact of baseline 
      variables on these effects. METHODS: PubMed, Embase, Web of Science, Cochrane 
      Library, and clinical trial registry websites were searched for randomized 
      controlled trials (RCTs) >/=24 weeks duration in adults with T2DM (PROSPERO: 
      CRD42022331547). Adjudicated cerebrovascular events in GLP-1RA treatment vs 
      control arms were pooled together to calculate risk ratios (RR) using 
      fixed-effects model. Subgroup analysis was performed based on individual drugs, 
      treatment duration, and baseline patient characteristics. Quality of evidence was 
      assessed using GRADE framework. RESULTS: We identified 28 RCTs involving 74 148 
      patients (57% male; median [range], age 58 [52-67] years, BMI 32 [25.4-37.2] 
      kg/m2, T2DM duration 9 [3.5-15.4] years, treatment duration 52 [24-259] weeks). 
      GLP-1RA use in T2DM was associated with significantly decreased risk of adverse 
      cerebrovascular outcomes vs placebo/active comparator (RR, 0.83; 95% CI, 
      0.76-0.91; I2 = 0%). Pooling data from cardiovascular outcome trials (n = 8), 
      GLP-1RA treatment vs placebo was associated with reduced risk of nonfatal stroke 
      (RR, 0.85; 95% CI, 0.76-0.94; I2 = 0%) but not fatal stroke (RR, 0.80; 95% CI, 
      0.61-1.05; I2 = 0%). GLP-1RA use was associated with reduced risk of ischemic 
      stroke (RCTs = 12; RR, 0.73; 95% CI, 0.60-0.89; I2 = 0%), composite of ischemic 
      stroke/TIA (RCTs = 16; RR, 0.76; 95% CI, 0.65-0.90; I2 = 0%), but not hemorrhagic 
      stroke (RCTs = 3; RR, 0.92; 95% CI, 0.51-1.64; I2 = 0%). Treatment benefits 
      differed according to baseline eGFR and diabetes duration (P interaction < .1). 
      Benefits were statistically significant for dulaglutide, subcutaneous/oral 
      semaglutide (P < .05). Sensitivity analysis, excluding shorter-acting 
      lixisenatide, eliminated the heterogeneity between individual GLP-1RA effects. 
      CONCLUSION: GLP-1RAs, particularly longer-acting formulations, reduced ischemic 
      cerebrovascular events in T2DM. Observed benefits were significantly higher in 
      patients with shorter T2DM duration and higher eGFR.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the 
      Endocrine Society. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Banerjee, Mainak
AU  - Banerjee M
AUID- ORCID: 0000-0002-6656-8569
AD  - Department of Endocrinology, Institute of Post Graduate Medical Education and 
      Research, Kolkata 700020, India.
FAU - Pal, Rimesh
AU  - Pal R
AD  - Department of Endocrinology, Post Graduate Institute of Medical Education and 
      Research, Chandigarh 160012, India.
FAU - Mukhopadhyay, Satinath
AU  - Mukhopadhyay S
AD  - Department of Endocrinology, Institute of Post Graduate Medical Education and 
      Research, Kolkata 700020, India.
FAU - Nair, Kirthana
AU  - Nair K
AD  - Department of Endocrinology, Post Graduate Institute of Medical Education and 
      Research, Chandigarh 160012, India.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
SB  - IM
CIN - J Clin Endocrinol Metab. 2023 Apr 03;:. PMID: 37009694
MH  - Male
MH  - Adult
MH  - Humans
MH  - Middle Aged
MH  - Female
MH  - Hypoglycemic Agents/adverse effects
MH  - Glucagon-Like Peptide-1 Receptor/agonists
MH  - *Ischemic Attack, Transient/chemically induced/drug therapy
MH  - Randomized Controlled Trials as Topic
MH  - *Diabetes Mellitus, Type 2/complications/drug therapy/chemically induced
MH  - *Ischemic Stroke/chemically induced/drug therapy
MH  - *Stroke/epidemiology/etiology/prevention & control
OTO - NOTNLM
OT  - GLP-1 receptor agonists
OT  - T2DM
OT  - cardiovascular outcome
OT  - ischemic stroke
OT  - mortality
OT  - transient ischemic attacks
EDAT- 2023/02/18 06:00
MHDA- 2023/06/19 13:08
CRDT- 2023/02/17 12:33
PHST- 2022/12/27 00:00 [received]
PHST- 2023/06/19 13:08 [medline]
PHST- 2023/02/18 06:00 [pubmed]
PHST- 2023/02/17 12:33 [entrez]
AID - 7044761 [pii]
AID - 10.1210/clinem/dgad076 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2023 Jun 16;108(7):1806-1812. doi: 
      10.1210/clinem/dgad076.