BACKGROUNDLong-term glycemic control reduces retinopathy risk, but transient worsening can occur with glucose control intensification. Glucagon-like peptide 1 receptor agonists (GLP-1RA) lower glucose, but the long-term impact on retinopathy is unknown. GLP-1RA cardiovascular outcome trials (CVOTs) provide long-term follow-up, allowing examination of retinopathy outcomes.
PURPOSETo examine the associations between retinopathy, HbA 1c , systolic blood pressure (SBP), and weight in GLP-1RA CVOTs.
DATA SOURCESSystematic review identified six placebo-controlled GLP-1RA CVOTs reporting prespecified retinopathy outcomes.
STUDY SELECTIONPublished trial reports were used as the primary data sources.
DATA EXTRACTIONHbA 1c , SBP, and weight data throughout follow-up by treatment group were extracted.
DATA SYNTHESISRandom-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 (I 2 5 52.2%; Q statistic P 5 0.063). Univariate meta-regression showed an association betweenretinopathyandaverageHbA 1c reductionduringtheoverallfollow-up(slope 5 0.77, P 5 0.007), but no relationship for SBP or weight. Sensitivity analyses for HbA 1c showed a relationship at 3 months (P 5 0.006) and 1 year (P 5 0.002). A 0.1% (1.09 mmol/mol) increase in HbA 1c reduction was associated with 6%, 14%, or 8% increased Ln(OR) for retinopathy at the 3-month, 1-year, and overall follow-up, respectively.
LIMITATIONSCVOTs were not powered to assess retinopathy outcomes and differed in retinopathyrelated criteria and methodology. The median follow-up of 3.4 years is short compared with the onset of retinopathy.
CONCLUSIONSHbA 1c reduction was significantly associated with increased retinopathy risk in metaregression for GLP-1RA CVOTs. The magnitude of HbA 1c 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 was unmeasured in these studies.Retinopathy status should be assessed whenintensifying glucose-loweringtherapy.
IMPORTANCEHospitalized patients with COVID-19 pneumonia have high rates of morbidity and mortality. OBJECTIVE To assess the efficacy of colchicine in hospitalized patients with COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS The Estudios Clínicos Latino América (ECLA) Population Health Research Institute (PHRI) COLCOVID trial was a multicenter, open-label, randomized clinical trial performed from April 17, 2020, to March 28, 2021, in adults with confirmed or suspected SARS-CoV-2 infection followed for up to 28 days. Participants received colchicine vs usual care if they were hospitalized with COVID-19 symptoms and had severe acute respiratory syndrome or oxygen desaturation. The main exclusion criteria were clear indications or contraindications for colchicine, chronic kidney disease, and negative results on a reverse transcription-polymerase chain reaction test for SARS-CoV-2 before randomization. Data were analyzed from June 20 to July 25, 2021. INTERVENTIONS Patients were assigned in a 1:1 ratio to usual care or usual care plus colchicine.Colchicine was administered orally in a loading dose of 1.5 mg immediately after randomization, followed by 0.5 mg orally within 2 hours of the initial dose and 0.5 mg orally twice a day for 14 days or discharge, whichever occurred first.
MAIN OUTCOMES AND MEASURESThe first coprimary outcome was the composite of a new requirement for mechanical ventilation or death evaluated at 28 days. The second coprimary outcome was death at 28 days. RESULTS A total of 1279 hospitalized patients (mean [SD] age, 61.8 [14.6] years; 449 [35.1%] women and 830 [64.9%] men) were randomized, including 639 patients in the usual care group and 640 patients in the colchicine group. Corticosteroids were used in 1171 patients (91.5%). The coprimary outcome of mechanical ventilation or 28-day death occurred in 160 patients (25.0%) in the colchicine group and 184 patients (28.8%) in the usual care group (hazard ratio [HR], 0.83; 95% CI, 0.67-1.02; P = .08). The second coprimary outcome, 28-day death, occurred in 131 patients (20.5%)in the colchicine group and 142 patients (22.2%) in the usual care group (HR, 0.88; 95% CI, 0.70-1.12). Diarrhea was the most frequent adverse effect of colchicine, reported in 68 patients (11.3%).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.