ECO 2026
More weight lost on GLP-1s, fewer obesity complications
Clinical Takeaway: How much weight patients actually lose on a GLP-1 may matter more than simply being on one. Adherence support and follow-up are central to the benefit.
GLP-1 drugs reduce weight and improve health outcomes in randomized trials, but real-world weight changes vary widely from patient to patient. Whether those differences translate into different risks of obesity-related complications has not been well established. This analysis tested that connection.
The amount of weight lost tracks closely with risk reduction. Compared with patients who lost less than 5% of body weight, those who lost 15% or more had 37% lower risk of osteoarthritis, 30% lower risk of chronic kidney disease, and 69% lower risk of obstructive sleep apnea. Heart failure risk dropped 32% in this group but did not reach statistical significance.
Patients who gained weight in the first year saw the opposite. Sleep apnea risk was 22% higher and heart failure risk was 69% higher. Osteoarthritis (10%) and kidney disease (14%) risks trended higher but did not reach significance. The contrast between losing even a little weight and gaining weight was nearly as striking as the contrast between high and low responders.
Weight outcomes varied widely. About 79% of patients lost some weight in the first year, but most lost less than 10%; only 30% reached losses of 10% or more, and roughly 1 in 5 actually gained weight. Half the cohort discontinued their GLP-1 within a year, which likely accounts for much of the modest-loss and weight-gain groups.
The analysis covered 89,718 US adults who started liraglutide, semaglutide, or tirzepatide between January 2021 and June 2024, with outcomes tracked through June 2025. Mean age was 57.5 years, mean BMI was 34.7, and 61% had type 2 diabetes. Roughly half of the patients discontinued their GLP-1 within a year. First-year BMI change was measured 9 to 15 months after initiation, and patients were grouped by percent change in BMI. The cohort was analyzed regardless of whether patients stayed on therapy. Results are not peer-reviewed and the study was funded by Amgen.
Given that half of patients discontinued within a year and that benefit tracked closely with how much weight was lost, the clinical question is whether systems can keep patients engaged long enough to reach and maintain the weight loss thresholds where the protection against obesity complication is present.
"Not losing weight was associated with worse clinical outcomes while larger reductions were associated with decreased risks. These findings highlight the potential clinical importance of achieving and maintaining weight loss after GLP-1-based treatment initiation," the authors concluded.
Source: Wilding J. ECO 2026. Abstract 0217. First-Year BMI Change After GLP-1-Based Treatment Initiation and Risk of Subsequent Adverse Clinical Outcomes