New research to be presented at this year's European Congress on Obesity (ECO 2026, Istanbul, Turkey, 12-15 May) shows that, following treatment for obesity or diabetes or both using incretin-based drugs, losing more weight versus less weight, and losing a little weight versus gaining weight, both lead to relatively lower risk of obesity-related conditions. The study is by Professor John Wilding of the University of Liverpool, UK, and colleagues.
In randomised trials, glucagon-like peptide-1 (GLP-1)-based treatments (semaglutide/liraglutide) and GLP-1/GIP (Glucose-dependent Insulinotropic Polypeptide) dual agonists (tirzepatide) lead to weight reduction and decreased risk for adverse clinical outcomes. In real-world settings, discontinuation of GLP-1-based treatments is common and there is substantial heterogeneity in weight change. Whether real-world weight change following GLP-1–based treatment initiation is associated with subsequent risk of adverse clinical outcomes is not well established. As such, the authors investigated this risk.
Using Optum Market Clarity, a US-based electronic health record and claims database, the authors calculated first-year BMI change after initiation of GLP-1-based treatment (liraglutide, semaglutide, tirzepatide) between January 2021 and June 2024 and assessed associations with subsequent clinical outcomes through June 2025. First-year BMI change was defined as the change from baseline to the mean BMI of all measurements from 275 to 455 days following initiation. They then assessed the association of BMI change with the risk of incident osteoarthritis, chronic kidney disease (CKD), obstructive sleep apnea (OSA), and heart failure, and estimated hazard ratios (HRs) after adjustment for demographic and clinical characteristics. Patients who experienced an outcome prior to their follow-up BMI measurements were excluded.
The study included 67,841 (75.6%) patients who initiated semaglutide, 15,661 (17.5%) tirzepatide, and 6,216 (6.9%) liraglutide. Upon treatment initiation, the mean age was 57.5 years and BMI was 34.7 kg/m2, and 61% had type 2 diabetes. Overall, half (50.1%) of patients discontinued GLP-1-based treatment, defined by a 60-day or longer gap without medication, within one year of initiation. The study analysed the whole cohort based on how much weight was lost, regardless of whether they continued or discontinued therapy.
In the year following treatment initiation, 27.0%, 22.4%, 14.1%, and 15.8% of patients had reductions in BMI of <5%, 5% to <10%, 10% to <15%, and ≥15%, respectively, while 20.8% experienced an increase in BMI. The incidence rate per 1,000 person-years over the subsequent mean follow-up of 11 months (meaning the 11 months after the initial year of treatment) was 21.4 for osteoarthritis, 21.1 for CKD, 20.3 for OSA, and 3.9 for heart failure.
Compared to patients with a BMI reduction of 0 to <5%, the odds for those who experienced a BMI reduction of at least 15% were 37% lower for osteoarthritis, 30% lower for CKD, 69% lower for OSA, and 32% lower for heart failure (with all results statistically significant except that for heart failure).
The odds for patients with an increase in BMI having these outcomes versus a person with 0 to <5% BMI reduction was a 10% higher for osteoarthritis (a trend, not statistically significant), 14% higher for CKD (borderline significant), 22% higher for OSA, and 69% higher for heart failure (both statistically significant) (see Figure full abstract).The authors conclude: "In this real-world study where half of patients discontinued GLP-1-based treatment within a year after initiation, 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."
