<a><b>Background: </b></a>Long-term glycemic control reduces
retinopathy risk, but transient worsening can occur with glucose control
intensification. GLP-1 receptor agonists (RA) lower glucose, but long-term
impact on retinopathy is unknown. GLP-1RA cardiovascular outcome trials (CVOTs)
provide long-term follow-up, allowing examination of retinopathy outcomes.
<p><b>Purpose:
</b>To
examine the associations between retinopathy, HbA1c, systolic blood pressure
(SBP) and weight in GLP-1RA CVOTs. </p>
<p><b>Data
Sources: </b>Systematic
review identified 6 placebo-controlled GLP-1RA CVOTs reporting prespecified
retinopathy outcomes. </p>
<p><b>Study
Selection: </b>Published
trial reports were used as primary data sources. </p>
<p><b>Data
Extraction: </b>HbA1c,
SBP, and weight data throughout follow-up by treatment group were extracted. </p>
<p><b>Data
Synthesis: </b>Random
effects model meta-analysis showed no association between GLP-1RA treatment and
retinopathy (odds ratio [OR] 1.10; 95% CI 0.93, 1.30), with high heterogeneity
between studies (I2=52.2%; Q-statistic p=0.063). Univariate meta-regression
showed an association between retinopathy and average HbA1c reduction during
the overall follow-up (slope=0.77, p=0.007), but no relationship for SBP or
weight. Sensitivity analyses for HbA1c showed a relationship at 3 months
(p=0.006) and 1 year (p=0.002). A 0.1% (1.09 mmol/mol) increase in HbA1c
reduction was associated with 6%, 14%, or 8% increased ln (OR) for retinopathy
at the 3-month, 1-year, and overall follow-up, respectively.<b> </b></p>
<p><b>Limitations:
</b>CVOTs
were not powered to assess retinopathy outcomes and differed in
retinopathy-related criteria and methodology. The median follow-up of 3.4 years
is short compared to the onset of retinopathy.<b> </b></p>
<p><b>Conclusions:
</b>HbA1c
reduction was significantly associated with increased retinopathy risk in
meta-regression for GLP-1RA CVOTs. The magnitude of HbA1c reduction was
correlated with retinopathy risk in people with diabetes and additional
cardiovascular risk factors, but the long-term impact of improved glycemic
control on retinopathy is unmeasured in these studies. Retinopathy status
should be assessed when intensifying glucose-lowering therapy. </p>
HbA1c Change and Diabetic Retinopathy During GLP-1 Receptor Agonist Cardiovascular Outcome Trials: A Meta-analysis and Meta-regression
