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The STEP 1 trial assessed once-weekly semaglutide 2.4 mg plus lifestyle intervention in adults with overweight or obesity without diabetes. After 68 weeks, average body-weight reduction was substantially greater with semaglutide than with placebo, and a greater proportion of treated participants achieved clinically meaningful weight-loss thresholds. Improvements were also seen in cardiometabolic measures and physical-function-related outcomes. The study is relevant to internal medicine because effective obesity treatment can influence hypertension, dysglycemia, lipids and broader cardiovascular risk. However, it also highlights the chronic nature of pharmacologic weight management: after treatment discontinuation, substantial weight regain can occur, emphasizing the need for long-term management rather than short courses. For physicians, the practical approach includes assessing obesity-related complications, setting realistic weight goals, monitoring gastrointestinal tolerability and reinforcing behavioral support. Drug therapy should complement—not replace—nutritional and activity interventions. STEP 1 helped establish modern anti-obesity pharmacotherapy as a legitimate part of comprehensive chronic disease care.
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The STEP 1 trial assessed once-weekly semaglutide 2.4 mg plus lifestyle intervention in adults with overweight or obesity without diabetes. After 68 weeks, average body-weight reduction was substantially greater with semaglutide than with placebo, and a greater proportion of treated participants achieved clinically meaningful weight-loss thresholds. Improvements were also seen in cardiometabolic measures and physical-function-related outcomes. The study is relevant to internal medicine because effective obesity treatment can influence hypertension, dysglycemia, lipids and broader cardiovascular risk. However, it also highlights the chronic nature of pharmacologic weight management: after treatment discontinuation, substantial weight regain can occur, emphasizing the need for long-term management rather than short courses. For physicians, the practical approach includes assessing obesity-related complications, setting realistic weight goals, monitoring gastrointestinal tolerability and reinforcing behavioral support. Drug therapy should complement—not replace—nutritional and activity interventions. STEP 1 helped establish modern anti-obesity pharmacotherapy as a legitimate part of comprehensive chronic disease care.
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