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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%).

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