Injectable weight-loss drugs deliver lower results in real-world use, study shows
Semaglutide and tirzepatide, injectable medications prescribed for obesity, are producing smaller weight loss in everyday clinical use than in trials, mainly due to early treatment discontinuation and lower maintenance doses, a large study has found.
Researchers tracking 7,881 adults with severe obesity found a notable gap between the weight loss achieved in randomised trials and in real-world settings with these GLP-1 medications.
The Cleveland Clinic-led study found that more than half of patients either stopped treatment within the first year or were on lower maintenance doses than recommended—both factors that reduced the drugs’ effectiveness.
Hamlet Gasoyan is lead author and researcher at Cleveland Clinic’s Center for Value-Based Care Research.
The researcher said: “Our study shows that patients treated for obesity with semaglutide or tirzepatide lost less weight on average in a regular clinical setting compared to what is observed in randomised clinical trials,.
“According to our data, this could be explained by higher rates of discontinuation and lower maintenance dosages used in clinical practice, compared to randomised clinical trial settings.”
Semaglutide, sold under brand names Wegovy and Ozempic, and tirzepatide, sold as Zepbound and Mounjaro, are approved to treat type 2 diabetes and long-term weight management.
They work by mimicking hormones that regulate appetite and blood sugar.
The study included patients who began treatment between 2021 and 2023, all with a body mass index (BMI) above 39—classed as clinically severe obesity.
Of the participants, 1,320 had prediabetes at the start of the study, defined by blood sugar levels between 5.7 and 6.4 per cent.
Researchers grouped participants based on when they discontinued treatment: early (within three months), late (between three and 12 months), or not at all.
The follow-up period ended in December 2024.
More than 20 per cent of patients discontinued their medications within three months, and 32 per cent stopped between three and 12 months.
Over 80 per cent of patients were on lower-than-recommended maintenance doses—1mg or less for semaglutide and 7.5mg or less for tirzepatide.
Among those who discontinued early, the average weight loss after one year was 3.6 per cent.
Patients who stopped later lost 6.8 per cent on average, while those who continued throughout the year lost 11.9 per cent.
The highest reductions were observed in those who stayed on high maintenance doses, with average weight loss of 13.7 per cent for semaglutide and 18 per cent for tirzepatide.
Researchers also identified several factors linked to achieving clinically significant weight loss of 10 per cent or more.
Patients had higher odds of meeting this threshold if they remained on treatment, took higher doses, used tirzepatide rather than semaglutide, or were female.
In participants with prediabetes, those who continued treatment had better blood sugar outcomes.
Just 33 per cent of those who stopped early achieved normal HbA1c levels (5.6 per cent or lower), compared to 41 per cent of late discontinuers, and 67.9 per cent of those who remained on treatment.
Dr Gasoyan said: “In our study, the majority of the patients with prediabetes experienced normal blood sugar levels when they continued their treatment.
“Type 2 diabetes is one of the most common complications of obesity, so diabetes prevention is very important.
“This study highlights that treatment discontinuation, especially early, negatively affects both weight and glycaemic control outcomes.”
The most common reasons for stopping treatment included cost, insurance coverage issues, side effects, and medication shortages.
Although patients who discontinued treatment lost less weight overall, their weight tended to remain stable afterwards, suggesting some may have adopted alternative weight management strategies.
A follow-up study is planned to explore why patients stop treatment and what other approaches they may use.
