The clinical efficacy of GLP‑1 receptor agonists (GLP‑1RAs) such as semaglutide and tirzepatide has been well established in large-scale randomized trials, with reported average weight losses ranging from 15% to 21%. However, the real-world performance of these medications is often hindered by challenges in dose escalation, treatment adherence, and long-term persistence.
A new study published in Diabetes, Obesity and Metabolism (Samuels et al., 2025) provides one of the most comprehensive real-world evaluations of GLP‑1RA usage to date. Conducted in a multidisciplinary academic obesity clinic in the United States, the study tracked over 2,300 adult patients prescribed semaglutide or tirzepatide between January 2022 and December 2024. The findings offer a rare and valuable window into how these medications perform outside of trial settings, even under highly supportive conditions.
A Real-World Setting with Ideal Support
What makes this study stand out is its unique clinical environment. All patients were enrolled in a Medical Weight Loss Bundle—a value-based care program providing comprehensive, no-cost access to obesity care. The bundle included appointments with physicians and dietitians trained in obesity medicine, mental health support, diagnostic testing, and full coverage for prescribed medications.
Despite these optimal conditions, only 23% of semaglutide users reached the 2.4 mg target dose, and just 28% of tirzepatide users reached 15 mg. The majority remained at submaximal doses, reflecting ongoing challenges in tolerability, titration logistics, and possibly patient hesitation—even with expert guidance and cost barriers removed.
Persistence: A Critical Drop-Off Point
The study’s most striking finding may be its data on treatment persistence. While clinical trials report discontinuation rates under 10%, Samuels et al. observed that only 50% of patients remained on GLP‑1RA therapy at 12 months. The median duration of use was 10.7 months, with clear attrition at each timepoint: 14% had discontinued by 3 months, 24% by 6 months, and 35% by 9 months.
This suggests that real-world dropout rates are high—even in best-case scenarios. For comparison, prior retrospective studies using insurance claims data have shown that fewer than 30% of patients remain on therapy after one year. That this pattern persists even in a tightly coordinated academic program underscores the complexity of sustaining long-term GLP‑1RA treatment.
Weight Loss Outcomes Approaching Clinical Trial Benchmarks
Encouragingly, the patients who did persist on treatment experienced meaningful and sustained weight loss. Among those adherent for at least 6 months, the median total weight loss (TWL) was 9.4%. Those remaining on therapy for 12 months lost 14.4% of their body weight on average—approaching the outcomes seen in the STEP and SURMOUNT trials.
Patients who used semaglutide exclusively achieved a 12-month TWL of 15.6%, while tirzepatide-only users lost 14.1%. These outcomes confirm that GLP‑1RAs remain highly effective—but primarily for those who maintain consistent use over time.
Titration and Switching Patterns
The study also documented frequent switching between medications. A quarter of the cohort (575 patients) used both semaglutide and tirzepatide at different points. Titration trajectories revealed slow progression to high doses, with many patients plateauing below recommended maintenance levels. Only 22.9% of semaglutide users reached 2.4 mg, and 28.3% of tirzepatide users reached 15 mg.
Interestingly, in multivariable models, high-dose users did experience statistically greater weight loss (14.7 kg/year vs. 13.6 kg/year), but the clinical significance of this 1.1 kg difference remains limited—particularly given the high rate of missing data at later timepoints.
Safety Profile: GI Side Effects Still Dominant
The incidence of emergency department (ED) visits or hospitalizations related to GLP‑1RA therapy was 13.6%, with gastrointestinal issues (reflux, constipation, abdominal pain) being the most common cause. Only a single case of acute pancreatitis was reported. This aligns with the known side-effect profile of these agents and confirms their generally favorable safety in a monitored setting.
Why This Study Matters
This study is one of the first to demonstrate that **real-world GLP‑1RA outcomes can closely mirror clinical trials—**but only under very specific conditions:
- Structured, multidisciplinary care
- Continuous patient education and support
- Elimination of financial barriers
- Consistent clinical follow-up and titration guidance
Yet even in this idealized context, the study observed suboptimal titration, high discontinuation rates, and variable weight outcomes. In typical primary care or non-specialized settings, it is likely that outcomes are even less favorable.
These findings highlight a critical insight: pharmacological efficacy is not enough. To truly unlock the potential of GLP‑1 therapies, behavioral, educational, and structural support must be integrated into the care model.
The Case for Companion Therapeutics
For digital health innovators and clinicians alike, the implications are clear. The success of semaglutide and tirzepatide depends not just on the molecule, but on the ecosystem that surrounds it. This study strongly supports the development of digital companion tools that offer:
- Real-time management of side effects
- Personalized titration support
- Behavioral coaching and adherence reinforcement
- Data-driven feedback and weight tracking
At Boli, we believe this is not just a complementary service—it is an essential extension of care. As GLP‑1 usage expands, scalable, personalized digital support will be key to ensuring that more patients not only start, but succeed with their treatment.
Reference
Samuels JM, Ye F, Irlmeier R, et al. (2025). Real-world titration, persistence & weight loss of semaglutide and tirzepatide in an academic obesity clinic. Diabetes Obesity and Metabolism. https://doi.org/10.1111/dom.70004
