IPM Take
The first generation of obesity drug policy has been built around a crude question: should patients stay on treatment or stop?
SURMOUNT-MAINTAIN suggests the more useful question may be how much treatment does an individual patient need to maintain the health gains they have already achieved?
After 60 weeks of tirzepatide at a maximum tolerated dose of 10 or 15 mg, participants who stepped down to 5 mg retained substantially more weight loss and cardiometabolic improvement over the following year than those switched to placebo. They did not maintain as much as patients who continued full-intensity therapy, which means 5 mg should not be presented as an equivalent substitute for everyone.
That distinction is precisely where personalised medicine enters the story. Maintenance treatment could eventually be adjusted according to weight trajectory, blood pressure, glycaemia, lipids, tolerability, patient preference and perhaps cardiovascular risk, rather than treating maximum dose as the only successful destination.
The policy problem is that reimbursement systems are rarely designed around dynamic treatment intensity. They tend to ask whether a drug is covered, not what dose delivers sufficient value for a particular patient at a particular stage of chronic disease.
Obesity medicine is becoming sophisticated enough to ask that question. Payment policy now has to catch up.
Executive Summary
SURMOUNT-MAINTAIN was a 112-week Phase IIIb trial involving adults with obesity, or overweight with a weight-related comorbidity, without diabetes. Participants initially received maximum-tolerated tirzepatide, 10 or 15 mg, for 60 weeks. Those eligible for randomisation were then assigned to continue the maximum tolerated dose, reduce to 5 mg, or switch to placebo for a further 52 weeks.
At week 112, estimated body-weight reduction from original baseline was 21.9% with continued maximum-dose treatment, 16.6% after stepping down to 5 mg, and 9.9% after switching to placebo. The 5 mg strategy also preserved meaningful improvements in waist circumference, blood pressure, triglycerides and glycaemic measures.
Among participants with prediabetes at baseline, 84.4% of those receiving 5 mg were normoglycaemic at the end of the study, compared with 92.7% on maximum-tolerated therapy and 51.0% with placebo.
The ESC 2026 presentation extended this discussion by examining cardiometabolic parameters according to how successfully participants maintained weight reduction, placing the study explicitly within a session on personalised cardiovascular prevention.
The important limitation is that SURMOUNT-MAINTAIN was not a cardiovascular outcomes trial. Preserved blood pressure, lipid and glycaemic improvements are encouraging surrogate markers, but the study cannot establish that stepping down to 5 mg preserves the same protection against myocardial infarction, stroke or cardiovascular death as higher-dose treatment.
Why it matters
- HTA bodies: Maintenance dosing raises a different value question from initial weight-loss treatment. Assessment may eventually need to distinguish induction from maintenance and evaluate whether lower-intensity treatment can preserve clinically meaningful cardiometabolic benefits at lower burden or cost without sacrificing long-term outcomes.
- Payers: A binary reimbursement model of full treatment versus discontinuation may become increasingly difficult to defend if lower-dose maintenance proves sufficient for selected patients. Coverage policies will need to consider treatment duration, dose flexibility and monitoring rather than imposing arbitrary stopping rules based only on kilograms lost.
- Industry / innovation partners: The next competitive frontier in incretin medicine may not be maximum weight reduction. Evidence supporting personalised dose reduction, treatment maintenance and cardiometabolic targets could become increasingly important as patients remain on therapy for years rather than months.
The success of incretin-based obesity therapy has created a problem that the first wave of clinical trials was not designed to answer.
Once a patient has lost 15%, 20% or more of their body weight and improved their blood pressure, glucose regulation and lipid profile, what happens next?
Continuing the maximum dose indefinitely may preserve the largest treatment effect, but some patients may want to reduce treatment because of tolerability, preference, availability or cost. Stopping altogether has repeatedly been associated with weight regain and loss of some cardiometabolic improvements. SURMOUNT-MAINTAIN was designed to test the space between those two extremes.
The trial enrolled 441 adults, with 378 eventually randomised after a 60-week open-label period on tirzepatide at their maximum tolerated dose. Participants had obesity, or overweight with at least one related complication, and did not have type 2 diabetes. During the 52-week maintenance phase, they either continued 10 or 15 mg, stepped down to 5 mg, or switched to placebo.
The pattern was clear. Continuing full-intensity treatment preserved the most weight loss, but reducing the dose to 5 mg performed substantially better than discontinuation. At week 112, participants in the 5 mg group remained 16.6% below their original body weight on the study’s primary treatment estimand, compared with 21.9% in the maximum-dose group and 9.9% in the placebo group.
The cardiometabolic pattern moved in the same direction. At the end of follow-up, the 5 mg group remained around 16 cm below baseline waist circumference, systolic blood pressure was approximately 4.7 mmHg below baseline, triglycerides were around 19% lower and HbA1c remained about 0.41 percentage points lower. The corresponding improvements were generally larger with continued maximum-dose treatment and smaller after withdrawal.
The maintenance dose may need to become a clinical target
The policy significance is not that everyone should be reduced to 5 mg.
The European Heart Journal commentary on SURMOUNT-MAINTAIN makes the opposite point: lower-dose treatment preserved a meaningful proportion of benefit, but it was not equivalent to continued maximum-tolerated therapy. Dose reduction may be reasonable for selected patients when tolerability, excessive weight loss, preference, availability or cost becomes important, but it should be monitored rather than assumed to work equally well for everyone.
That turns obesity pharmacotherapy into a much more recognisable chronic-disease model.
Hypertension treatment is titrated against blood pressure. Diabetes therapy changes with HbA1c, complications and hypoglycaemia risk. Anticoagulation and lipid-lowering strategies are adjusted according to risk and response. There is little reason to assume that long-term obesity treatment should remain uniquely fixed at the dose that produced the initial maximum weight reduction.
A personalised maintenance strategy could instead ask whether the patient is maintaining weight, waist circumference, glycaemic control, blood pressure and metabolic improvement, while also considering adverse effects, treatment burden and preferences.
The ESC 2026 post hoc presentation is particularly interesting in that context because it examined cardiometabolic parameters according to the degree of maintained weight reduction, rather than treating weight itself as the only meaningful outcome.
That matters as tirzepatide itself moves deeper into cardiovascular medicine. Only days before the ESC analysis, the FDA expanded Mounjaro’s U.S. indication to reduce cardiovascular death, non-fatal myocardial infarction and non-fatal stroke in adults with type 2 diabetes at high cardiovascular risk, based on SURPASS-CVOT. The cardiovascular outcome trial established non-inferiority to dulaglutide, although superiority was not demonstrated.
The broader trajectory is clear: incretin therapy is becoming less about weight as an isolated cosmetic or numerical outcome and more about long-term cardiometabolic disease management.
Personalised dosing will collide with reimbursement policy
This creates an awkward question for payers.
Many reimbursement systems still approach obesity medicines as if treatment has a beginning and an end, often using eligibility thresholds, weight-loss targets or fixed treatment periods. SURMOUNT-MAINTAIN instead supports obesity as a chronic condition in which de-escalation may be possible for some patients, while discontinuation may be inappropriate for many.
A lower dose could also change the economics of treatment, although that depends heavily on national pricing and reimbursement structures rather than pharmacology alone. In the current U.S. LillyDirect self-pay programme, for example, 5 mg Zepbound is offered at a lower monthly price than higher maintenance strengths, illustrating how dose differentiation can translate into different expenditure under some payment arrangements.
But price should not become the clinical algorithm. If a patient requires 10 or 15 mg to maintain clinically important benefit, forcing dose reduction purely to reduce spending would not constitute personalised care. Conversely, continuing every stable patient indefinitely at the highest tolerated dose without testing whether lower intensity is sufficient may also represent inefficient treatment.
The missing evidence is outcomes.
SURMOUNT-MAINTAIN followed patients for one year after randomisation and measured weight and cardiometabolic markers, not heart attacks, strokes or cardiovascular mortality. The trial also included people without diabetes and does not establish a universal maintenance strategy across the much broader population now receiving tirzepatide.
Even so, the study changes the policy conversation in an important way. The choice may no longer be maximum-dose treatment forever or complete withdrawal.
For selected patients, there may be a third path: find the lowest treatment intensity that preserves the health outcome that matters to that individual, and keep measuring whether it still does.
That is a far more personalised model of cardiometabolic care.
