Abstract
Dear Editor,
Two questions central to any honest appraisal of Glucagon-Like Peptide-1 (GLP-1) receptor agonists in the Asia-Pacific deserve direct engagement: whether these agents are cost-effective compared with lifestyle intervention in low- and middle-income countries (LMICs), and whether long-term tolerance and weight regain undermine the case for their use. Both are legitimate. Both, when examined against the available evidence, strengthen rather than weaken the argument for equitable access, provided the clinical framing shifts, as it should, from weight management alone to cardiovascular risk reduction.
The cost-effectiveness evidence is nuanced, and its interpretation depends critically on which clinical outcome is being measured and in which health system context. A 2026 systematic review and meta-analysis of nine high-income country studies found that GLP-1 receptor agonists are not cost-effective for obesity treatment in patients without diabetes when evaluated from a payer perspective against lifestyle intervention alone. 1 This finding is important but should not be generalized uncritically to the Asia-Pacific context. First, the comparator in most included studies was structured lifestyle intervention delivered in well-resourced, high-income health systems, a standard that does not reflect the reality of most LMIC primary care settings, where dietary counselling, supervised exercise programmes, and behavioural support are either unavailable or inconsistently delivered. 2 Second, and more fundamentally, the clinical case in South and Southeast Asia is not primarily about weight management. It is about cardiovascular mortality. GLP-1 receptor agonists versus insulin in patients with type 2 diabetes demonstrate a cost-effective profile from both payer and health care sector perspectives, saving an estimated $19,391 per case of all-cause mortality prevented. 3 When the outcome of interest is cardiovascular death rather than weight loss, the economic calculus changes substantially.
LMIC microsimulation modelling across 79 countries found that introducing GLP-1 agonists into insulin-based regimens could reduce disability-adjusted life years lost to cardiometabolic complications by more than 50% per 1000 person-years, at a cost that, under tiered pricing or voluntary licensing frameworks, would fall well within regional willingness-to-pay thresholds. 4 A global modelling study estimated that universal access could avert 2.1 to 3.1 million deaths annually, with the majority of that preventable mortality concentrated in LMIC settings. 5 The relevant cost-benefit question for the Asia-Pacific region, therefore, is not whether these drugs are economically justified for weight loss in a private clinic; it is whether they are justified as part of a cardiovascular prevention strategy in a population carrying the world’s highest absolute burden of cardiometabolic disease, and the answer to that question is considerably more favourable.
A legitimate and frequently raised concern is whether long-term tolerance to GLP-1 receptor agonists and subsequent weight regain undermine their value as a sustainable public health strategy, and for weight management endpoints specifically, this concern has clinical merit. Discontinuation rates are high; more than half of the patients initiated on GLP-1 agonists for obesity do not persist beyond 12 weeks, 6 and weight regain following cessation is well documented. However, the cardiovascular benefit from these agents is not contingent on sustained weight loss. The Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial, which enrolled patients with obesity and established cardiovascular disease but no diabetes, demonstrated a 20% reduction in major adverse cardiovascular events (MACE) that emerged early and persisted throughout follow-up and was only partially explained by weight loss trajectories. 7 Anti-inflammatory, endothelial, and direct myocardial effects appear to contribute independently of adipose tissue reduction. This is a crucial distinction: a drug that loses its weight management benefit when discontinued does not necessarily lose its cardiovascular protection during the treatment period, and the cost-effectiveness of preventing a single non-fatal myocardial infarction or cardiovascular death in a 50-year-old in Pakistan or Bangladesh substantially outweighs the cost of treatment.
This does not diminish the importance of lifestyle intervention. Structured dietary modification, increased physical activity, and behavioural support remain the foundation of cardiometabolic risk management and carry advantages in cost, safety, and patient autonomy that pharmacotherapy cannot replicate. 2 The argument is not that GLP-1 agonists should replace lifestyle approaches in LMICs; it is that for patients with established cardiovascular disease, high MACE risk, or type 2 diabetes, the evidence supports their use as an adjunct, and that the current access architecture makes that option unavailable to the populations who need it most. Expanding access through voluntary licensing, pooled procurement, and integration into national non-communicable disease frameworks is not an argument against lifestyle intervention; it is an argument for giving LMIC clinicians and patients the same range of evidence-based options that are available elsewhere.
The Asia-Pacific region bears a disproportionate share of global cardiometabolic mortality, and its populations show a greater relative cardiovascular benefit from GLP-1 receptor agonists than Western trial cohorts. 8 Framing the access question around weight management sustainability misses the more important point: these are cardiovascular drugs that happen to cause weight loss, and the region’s cardiovascular burden is precisely where their benefit profile is most relevant. The conversation about cost-benefit in LMICs deserves to be had, but it must be had using the right outcome and the right comparator.
