Recent data from the EASD on GLP-1, GIP, glucagon and amylin receptor agonists, with impressive relative weight loss numbers, are reported left, right and center currently.
Even though weight loss is an important goal, especially for patients with high BMI, mean weight loss is still only part of the clinical story.
For a treatment intended to be used for years, I would also like to see one simple number prominently reported: What percentage of all randomized participants remained on treatment at the intended maintenance dose at the end of the trial?
Trial completion is not the same as treatment persistence. Treatment persistence is not the same as receiving the intended dose.
Some recent examples:
➡️ In REDEFINE 1 (CagriSema), approximately 88% completed treatment, but only 57% were receiving the maximum 2.4/2.4 mg dose at week 68 (74% tried at least once to reach max dose).https://www.nejm.org/doi/10.1056/NEJMoa2502081
➡️In TRIUMPH-2 (Retatrutide) only 57 % reached the 9 mg dose and 54% reached the 12 mg dose (75% remained on treatment. As a side note is the listing of AEs in table 3 quite concerning, as is the 8 bpm/min increase in resting heart rate during the initial phase. https://www.nejm.org/doi/full/10.1056/NEJMoa2604169
➡️In another trial just presented at EASD, eloralintide, a selective amylin receptor agonist was tested together with tirzepatide. Discontinuation because of adverse events ranged from 10.8% to 27.0%, depending on dose. https://investor.lilly.com/news-releases/news-release-details/lillys-eloratzp-combination-eloralintide-and-tirzepatide
These side-effects: vomiting, constipation, diarrhea, persistent nausea and dysesthesia can determine whether a patient is willing and able to continue treatment. As anyone involved in clinical trials know, “mild” or “moderate” is based on strict criteria, not always aligned with how the patients would have rated the AE.
Furthermore, clinical trials may also represent a best-case tolerability environment. Participants follow structured escalation schedules, are monitored regularly and receive substantially more counselling and assistance than many patients receive in routine care.
Real-world persistence is therefore essential context. Several studies have shown that “real-life” discontinuation is high. Although cost is a major barrier for continuing treatment, adverse events play a major role.
👉 The most effective obesity medicine is not necessarily the one producing the greatest mean weight loss under ideal trial conditions. It may be the one that patients can and want to continue taking long term.
