Liraglutide Doses Below 3.0 mg Show Real-World Benefit, but Cost Blocks Half of Patients

Obesity medicine has been transformed by GLP-1 receptor agonists, yet a new real-world study from Taiwan suggests that the highest approved dose of liraglutide may be neither necessary nor attainable for many patients. Writing in Endocrinology, Diabetes and Metabolism, Tu and colleagues report the results of a multicentre, single-arm, post-marketing surveillance study of liraglutide in adults with obesity, and their findings carry a message that extends far beyond the clinic: nearly half of the participants who failed to reach the approved 3.0 mg maintenance dose cited medication cost as the reason. Affordability, the authors of an accompanying commentary argue, is therefore not a peripheral inconvenience but a system-level determinant of dose attainment, treatment continuity and real-world effectiveness.

The trial evidence underpinning liraglutide 3.0 mg is robust. In the SCALE Obesity and Prediabetes randomized controlled trial published in the New England Journal of Medicine in 2015, Pi-Sunyer and colleagues demonstrated that 3.0 mg of liraglutide combined with lifestyle intervention produced significantly greater weight loss than placebo plus lifestyle measures. Maintenance studies, including the SCALE Maintenance trial, have underlined that continued treatment is needed to sustain that benefit, since weight regain typically becomes apparent within six to twelve months after GLP-1 discontinuation. But randomized trials enroll selected patients under ideal conditions, and the Taiwan surveillance study offers a window into what actually happens when the drug is deployed in routine care.

The technical design of the study matters for interpreting its results. As a single-arm, prospective, multicentre post-marketing surveillance study, it followed adults with obesity prescribed liraglutide in real clinical settings in Taiwan, tracking dose escalation, tolerability and weight outcomes. The headline finding is that clinically meaningful benefit may occur below the 3.0 mg target, supporting personalised rather than universal dose escalation. However, the commentary by Azhar Zafar and Carina Scarlata accompanying the paper urges caution in interpretation: this was a single-arm study that excluded participants who withdrew before follow-up, around half of the original cohort withdrew before week 13, and only 60 participants contributed to the week-26 analysis. The encouraging results in continuing users cannot establish comparative effectiveness, discontinuation outcomes or long-term weight maintenance.

The most consequential implementation finding is the cost signal. Forty-nine percent of participants who did not reach 3.0 mg cited medication cost as the barrier. In a health system where liraglutide is dispensed under surveillance but not universally reimbursed, the price of the drug functioned as a de facto dose-limiting mechanism. The commentary distinguishes this sharply from another common reason for submaximal dosing: gastrointestinal tolerability. When clinicians intentionally limit the dose because of nausea, vomiting or other adverse effects, that represents appropriate personalised medicine. When the dose is limited because the patient cannot afford the next increment, it represents an avoidable barrier to equitable treatment. The distinction is crucial for policy, because the two mechanisms demand entirely different responses.

Lower-dose success in this cohort may reflect four distinct mechanisms, according to the commentary. Lower exposure may have resulted from intentional dose limitation due to gastrointestinal tolerability, which is clinically appropriate; from cost constraints, which are a barrier to equitable care; from clinical preference based on individual risk-benefit assessment; or from other unmeasured factors. Without stratifying these mechanisms, it is impossible to tell whether lower-dose treatment represents a reproducible, clinically appropriate strategy or an artefact of selection bias. Analyses that relate achieved dose, duration, discontinuation reason and individual weight trajectory would help distinguish tolerable, sustainable treatment from treatment limited by systemic financial barriers.

The broader real-world evidence on GLP-1 persistence adds weight to these concerns. A narrative review published in Diabetes, Obesity and Metabolism by Heisey and colleagues documents substantial discontinuation rates for GLP-1 receptor agonists, with cost and tolerability emerging as principal drivers of dose escalation failure and early discontinuation. Real-world evidence increasingly documents the complex barriers to treatment persistence, and the Taiwan study illustrates how these barriers operate at the level of the individual prescription. When a patient stops escalating at 1.8 mg or 2.4 mg because the next step is unaffordable, the clinical record may show a stable dose, but the underlying story is one of treatment intensity rationed by ability to pay rather than clinical need.

Cost-limited dosing risks inequitable treatment intensity based on ability to pay rather than clinical need, and the commentary is explicit that obesity care must consider whether a sustainable dose can be achieved and maintained, not simply whether treatment is effective at the target dose. This reframing has significant implications for how success is measured in obesity medicine. A patient who achieves modest weight loss on a dose they can sustain for years may fare better in the long run than a patient who reaches the maximum dose but discontinues within months because of financial pressure. Reporting denominators at each time point, including weight outcomes for those who discontinue where feasible, would make the real-world picture more complete and allow clinicians and policymakers to see the full trajectory of treatment, not just the outcomes of those who persist.

The implications extend well beyond Taiwan. Although access pathways, reimbursement and service capacity differ between health systems, the affordability principle identified in Taiwan is directly applicable to publicly funded systems such as the NHS, where formulary restrictions and patient eligibility criteria similarly shape real-world practice patterns. Both contexts illustrate how healthcare policy and commissioning decisions function as de facto clinical decision-makers, determining which patients receive target doses and which receive cost-rationed submaximal doses. In systems where GLP-1 receptor agonists for obesity are restricted to specific specialist services or limited-duration prescribing, the same dynamic operates: the formulary, not the prescriber, may ultimately decide the dose.

What would better evidence look like? The commentary proposes that future pragmatic registries should follow participants for twelve to twenty-four months, sufficient time to capture seasonal patterns, medication persistence trends and longer-term weight trajectories. This duration matters because evidence indicates that weight regain typically becomes apparent within six to twelve months following GLP-1 discontinuation, as documented in a systematic review and nonlinear meta-regression published in EClinicalMedicine by Budini and colleagues. Registries should report dose exposure, persistence, discontinuation, outcomes, adverse events and barriers across socioeconomic and funding contexts. Only with this granularity can the field establish which submaximal doses are sustainable, for whom, and how obesity care can deliver equitable, durable benefit.

For now, the Taiwan study adds an important piece to the emerging real-world picture of GLP-1-based obesity care. Randomised studies support liraglutide 3.0 mg with lifestyle intervention, and maintenance studies underline the need to consider persistence rather than short-term loss alone. The surveillance data suggest that clinically meaningful benefit may be achievable below the maximum dose, opening the possibility of personalised dose selection that balances efficacy, tolerability and affordability. But the finding that cost was the reason for failed dose escalation in nearly half of those who did not reach 3.0 mg is a warning that cannot be ignored. If obesity treatment is to deliver on its promise, health systems must ensure that dose decisions are made on clinical grounds, not financial ones, and that the doses patients can afford are also the doses that can sustain their health over the long term.

Subject of Research: Medicine & Health

Article Title: Liraglutide Dose Affordability and Durability in Real‐World Obesity Care

Article References: Zafar, A., & Scarlata, C. (2026). Liraglutide Dose Affordability and Durability in Real‐World Obesity Care. Endocrinology, Diabetes & Metabolism, 9(6), Article e70364. https://doi.org/10.1002/edm2.70364

Image Credits: AI Generated

DOI: 10.1002/edm2.70364

Keywords: liraglutide, obesity, GLP-1 receptor agonists, drug affordability, real-world evidence, health equity, Taiwan, weight management, Dose, Affordability, Durability, Real