Off-Trial: Real-World Weight Loss on Tirzepatide and Semaglutide
Abstract
Background: GLP-1 receptor agonist trials are tightly controlled: standardized titration, intensive dietary counseling, frequent in-person follow-up, and rigorous exclusion criteria. The real world is none of those things. In a U.S. telehealth GLP-1 program, diet engagement, exercise, medication choice, dose timing, and out-of-pocket cost vary substantially from patient to patient. Whether trial-level efficacy translates into the outcomes a patient and clinician will actually see is an open question, and the answer matters, because telehealth is now where most GLP-1 prescribing happens.
Methods: We conducted a retrospective cohort study of 13,507 adults who used a single GLP-1 agent (tirzepatide or semaglutide) through the Mochi Health telehealth obesity program and had a documented six-month weight observation. The primary outcome was achievement of ≥10% total body weight loss at six months. To address selection bias in the tirzepatide–semaglutide comparison, we used 1:1 nearest-neighbor propensity-score matching on age, sex, baseline BMI, baseline weight, and comorbid diabetes, hypertension, dyslipidemia, and prior bariatric surgery (recorded at intake), with a 0.25 SD caliper on the propensity logit. We drew a directed acyclic graph (DAG) with a clinical co-author to make the identifying assumptions explicit and to mark where unobserved variables (insurance, socioeconomic status, concomitant medications such as metformin) limit causal interpretation. We report…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 13,507 participants or records.
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