The Weight of Expectation

When NICE approved tirzepatide for the treatment of obesity in 2024, many welcomed it as a turning point. Here was a powerful dual agonist (GLP-1RA/GIP-RA) backed by robust data and offered to a patient population long neglected in structured care.

Six months into the phased rollout, we find ourselves not in a revolution, but in a patchwork: high clinical need, low service readiness, widespread confusion over eligibility, and an undercurrent of concern that we’ve misunderstood the problem.

At a distance, this looks like progress; up close, it’s something else entirely: a system still treating obesity as an individual failure rather than a chronic condition shaped by environments, inequality and biology. And into this fractured reality, we’ve introduced a powerful new tool but not a framework to use it wisely.

Inconsistencies In NICE approval

Let’s begin by correcting a persistent misconception: tirzepatide is not subject to a mandatory two-year prescribing limit under NICE TA1026. That time cap applies to agents modelled for cost-effectiveness on a two-year horizon (notably semaglutide and liraglutide). Tirzepatide, by contrast, is approved for ongoing use if patients meet response thresholds, typically >5% weight loss after six months on the maximum tolerated dose alongside clinical judgement and safety monitoring.

What is not baked into the guidance, however, is the clear lesson from semaglutide: when treatment is stopped without structured follow-up, weight regain is common and cardiometabolic gains recede within a few years. The mechanism isn’t mysterious; remove the pharmacological counterforce while leaving environment and physiology unchanged, and the system reverts. The policy implication is plain:

If continuity and relapse planning are absent, long-term value dissolves even for the “right” drug.

The System We Haven't Built

The NHS, like most health systems, was never designed to manage a chronic disease driven by obesogenic environments at population scale. We built services to treat the consequences, such as type 2 diabetes, cardiovascular disease and metabolic liver disease far more comprehensively than we built services to treat the underlying causes.

In the UK the Tier 3 pathways remain under-commissioned and uneven. In practice, the interim commissioning guidance anticipates treatment for a small minority of those who meet NICE criteria in the first years of rollout; the often-quoted figure of around 22,000 patients over three years illustrates the gap between clinical eligibility and service capacity. That gap is not a reflection of weak evidence but of absent infrastructure: staffing, longitudinal monitoring, and the MDT wraparound care NICE effectively mandates.

We are phasing in access to match system limitations, not the scale or urgency of need. That is rationing by design, presented as strategy.

What QS212 Is Really Saying

NICE QS212 is, in effect, a quiet admission that prescribing without structured support is bad medicine. It asks for:

• Individualised plans before treatment begins
• Documented communication between specialists, GPs and patients;
• A year of structured follow-up after treatment is stopped, including tailored action plans, community support, self-monitoring and behavioural counselling.

The fact it needs stating tells its own story: the pace of pharmacological innovation has outrun the delivery scaffolding. In areas with little or no Tier 3 provision, responsibility collapses onto general practice: prescribe, monitor, taper and support inside a ten-minute consultation, without protected time, shared registries or interoperable data flows. QS212 governs NHS pathways; it does not meaningfully touch the burgeoning private market, where over 1.5 million people are accessing GLP-1/GIP-RA therapies with widely variable oversight. Governance can set a bar; it cannot, by itself, build the runway.

Private Expansion, Public Risk

The private market has grown to fill the vacuum, often faster than governance can keep pace. Many patients are outside MDT review, with limited baseline screening, sparse cardiometabolic monitoring, and no documented plan for discontinuation. Continuity is rare; integration with NHS records rarer still. When care is fragmented, safety signals are dimmed, and learning is lost. The country accrues experience without accumulating evidence.

Microdosing: Innovation or Experimentation?

Microdosing”—the use of sub-therapeutic or off-label low doses as a commercial model to soften side-effects, reduce cost, or broaden eligibility beyond classical obesity criteria.

It is attractive, marketable and, as things stand, largely untested for the outcomes that actually matter.

There are no peer-reviewed RCTs demonstrating that GLP-1 “microdosing” delivers durable cardiometabolic benefit, preserves lean mass, or reduces relapse versus established titration schedules. There is no agreed dose-response framework, and very little routine biomarker surveillance (HbA1c, lipid profile, inflammatory markers, body composition) in many private pathways. In the US where microdosing is being offered by using compounded products, sit outside standard licensing routes, and both MHRA and other regulators have issued warnings about unlicensed or compounded incretin supplies and the pharmacovigilance blind spots they create. In practical terms: if dose, product quality and follow-up are variable, so are outcomes and so is risk.

The core questions remain unanswered. Who benefits, at what dose, and on what measurable criteria? Who is monitoring lean mass and cardiometabolic status over time? Who is accountable for long-term safety when compounding circumvents the traceability built into licensed supply chains? Until those questions are answered with trials and linked real-world data, microdosing is best understood as a live experiment, not a treatment pathway.

A New Frontier: Gut Microbiome

GLP-1/GIP-RAs act on appetite regulation, insulin sensitivity, gastric emptying and lipid metabolism, but the story extends further through bile acid signalling, gut motility and the microbiome. Early studies suggest that microbial diversity and specific metabolite signatures may shape treatment response; dysbiosis may blunt efficacy, while certain profiles may potentiate it. In the clinic, this is visible in the heterogeneity we already see: similar people, similar doses, very different trajectories.

Yet we rarely measure gut health status at baseline or after treatment, and almost never relate it to dose adjustments or relapse planning. This is a missed opportunity. Integrating simple, standardised gut health measures into routine pathways, paired with dietary fibre strategies, polyphenol-rich foods and, in selected cases, targeted probiotics could allow dose optimisation, extend durability and build knowledge if tapering if appropriate. Precision metabolic care will require us to treat biology as a network, not a silo; the gut is not a footnote to appetite, it is part of the mechanism.

Moving From Hope to System

If we want to avoid repeating the cycle of promise, patchwork, ration we have to match innovation with infrastructure. That means investing where the outcomes are decided: locally, longitudinally, and transparently.

At a system level, that looks like ICB-backed, community-based metabolic services where Tier 3 is the floor, not the ceiling; protected MDT time; and explicit commissioning for coaching and behaviour support rather than assuming it can be conjured in primary care. It looks like national registries that track more than weight and include HbA1c, blood pressure, lipid profile, liver health, body composition, mental health and adverse events; shared across NHS and private providers with common data definitions so we can actually learn. It looks like baseline safety standards for all prescribers, regardless of sector, tied to contribution of outcomes data rather than self-declarations.

It also looks like embedded research where we continue to build evidence. Questions such as microbiome–incretin interactions, microdosing protocols, deprescribing frameworks, relapse prevention. These could be studied within NHS–academic collaboratives with transparent methods and open reporting.

And it looks like equity that is measured rather than asserted: access tracked by geography, ethnicity and deprivation, with ICBs held to account when postcode inequity persists.

Finally, it looks like workforce including coaching, behaviour change, dietetic input and physical activity support. Not as nice-to-haves to be shaved away when budgets tighten; they are the mechanisms by which pharmacology becomes durable health.

GLP-1/GIP-RA therapies have reignited hope for people living with obesity and multimorbidity. But hope alone is not a system. If these therapies genuinely address mechanisms that drive obesity, we have a responsibility to build services that address those mechanisms too. Without investment in infrastructure, linked data and integrative biology, governance becomes rationing and momentum stalls.

We can choose differently. Match the medicine with the means to use it well, and the “weight of expectation” becomes weight carried by a system, not by patients alone.