ImportanceType 2 diabetes (T2D) is the leading cause of kidney disease in the US. It is not known whether glucose-lowering medications differentially affect kidney function.ObjectiveTo evaluate kidney outcomes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) trial comparing 4 classes of glucose-lowering medications added to metformin for glycemic management in individuals with T2D.Design, Setting, and ParticipantsA randomized clinical trial was conducted at 36 sites across the US. Participants included adults with T2D for less than 10 years, a hemoglobin A1c level between 6.8% and 8.5%, and estimated glomerular filtration rate (eGFR) greater than or equal to 60 mL/min/1.73 m2 who were receiving metformin treatment. A total of 5047 participants were enrolled between July 8, 2013, and August 11, 2017, and followed up for a mean of 5.0 years (range, 0-7.6 years). Data were analyzed from February 21, 2022, to March 27, 2023.InterventionsAddition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin, with the medication combination continued until the HbA1c was greater than 7.5%; thereafter, insulin was added to maintain glycemic control.Main Outcomes and MeasuresChronic eGFR slope (change in eGFR between year 1 and trial end) and a composite kidney disease progression outcome (albuminuria, dialysis, transplant, or death due to kidney disease). Secondary outcomes included incident eGFR less than 60 mL/min/1.73 m2, 40% decrease in eGFR to less than 60 mL/min/1.73 m2, doubling of urine albumin-to-creatinine ratio (UACR) to 30 mg/g or greater, and progression of Kidney Disease Improving Global Outcomes stage. Analyses were intention-to-treat.ResultsOf the 5047 participants, 3210 (63.6%) were men. Baseline characteristics were mean (SD) age 57.2 (10.0) years; HbA1c 7.5% (0.5%); diabetes duration, 4.2 (2.7) years; body mass index, 34.3 (6.8); blood pressure 128.3/77.3 (14.7/9.9) mm Hg; eGFR 94.9 (16.8) mL/min/1.73 m2; and median UACR, 6.4 (IQR 3.1-16.9) mg/g; 2933 (58.1%) were treated with renin-angiotensin-aldosterone inhibitors. Mean chronic eGFR slope was −2.03 (95% CI, −2.20 to −1.86) mL/min/1.73 m2 per year for patients receiving sitagliptin; glimepiride, −1.92 (95% CI, −2.08 to −1.75) mL/min/1.73 m2 per year; liraglutide, −2.08 (95% CI, −2.26 to −1.90) mL/min/1.73 m2 per year; and insulin glargine, −2.02 (95% CI, −2.19 to −1.84) mL/min/1.73 m2 per year (P = .61). Mean composite kidney disease progression occurred in 135 (10.6%) patients receiving sitagliptin; glimepiride, 155 (12.4%); liraglutide, 152 (12.0%); and insulin glargine, 150 (11.9%) (P = .56). Most of the composite outcome was attributable to albuminuria progression (98.4%). There were no significant differences by treatment assignment in secondary outcomes. There were no adverse kidney events attributable to medication assignment.Conclusions and RelevanceIn this randomized clinical trial, among people with T2D and predominantly free of kidney disease at baseline, no significant differences in kidney outcomes were observed during 5 years of follow-up when a dipeptidyl peptidase 4 inhibitor, sulfonylurea, glucagonlike peptide 1 receptor agonist, or basal insulin was added to metformin for glycemic control.Trial RegistrationClinicalTrials.gov Identifier: NCT01794143

Background Repeated use of chemical irritants for crowd-control by local and federal law enforcement during sustained racial justice protests in the U.S. has raised concerns about potential adverse health effects. The objective of this study was to describe the health consequences of exposure to tear gas agents and associated healthcare utilization among adults reporting recent exposure to tear gas.Methods A cross-sectional, self-administered web-based survey of a convenience sample of 2,257 adults reporting recent exposure to tear gas in Portland, Oregon (U.S.), administered between July 30, 2020-August 20, 2020. Descriptive analyses were conducted on socioeconomic characteristics, reported health issues, utilization of healthcare services, and frequency of exposure to tear gas. Associations between reported mental health issues, healthcare utilization and race and/or ethnic categories were assessed using chi-square tests. For tests of association, racial and/or ethnic categories were divided into White/Non-Hispanic only and all other racial/ethnic categories due to a small number of Black, American Indian or Alaska Native, Asian/Pacific Islander, Hispanic participants and participants with multiple race and/or ethnic background. Effect sizes for the differences were expressed as Cramer’s V, a metric that measures associations between nominal responses. The Cochran-Armitage trend test was used to assess the relationship between health issues and the number of days of exposure to tear gas (i.e., a proxy dose of exposure) grouped into 1 day, 2-4 days, and ≥5 days. Missing data (item non-response) were omitted from the analysis.Results Almost all respondents (2,116; 93.8%) reported physical (2,114; 93.7%) or psychological (1,635; 72.4%) health issues experienced immediately after (2,105; 93.3%) or days following (1,944; 86.1%) the exposure. A slightly higher proportion experienced delayed head or gastrointestinal tract issues compared with immediate complaints. The majority (1,233; 54.6%) reported receiving or planning to seek medical or mental care. We observed a positive exposure-response trend for all except mouth-related delayed issues (p<0.01).Conclusion Persons exposed to tear gas agents reported physical and psychological health issues over a multiple-day period. Health issues reported increased with the exposure, indicating a potential dose-response; these health effects often led to healthcare utilization. This study provides evidence of potential unexpected harms of tear gas in civilians.