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Because comparator groups often differ in treatment indication, disease duration and comorbidity profiles, residual confounding remains a primary concern, necessitating caution in causal inference. In a research letter published in Diabetes, Obesity and Metabolism , researchers obtained data from adults in the TriNetX database from January 2006 to October 2024

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In the LOOK-AHEAD study, 5145 participants aged 4576 years (mean BMI 36 kg/m 2 ) with T2D were randomized to either calorie restriction or diabetes support and education intervention (controls) [33]