But obesity is not just a headline grabber; it is a critical global health issue. As Brian Buntz of Drug Discovery Trends wrote, in the US alone the obesity epidemic affects 40% of American adults. Yet, the US is not the most obese country in the world: the World Population Review listed the United States at number 18 globally in 2022, with American Samoa, Tonga, and Nauru taking the ‘top’ spots. According to the World Health Organization (WHO) that same year, one in eight people in the world were living with obesity. By 2024, 35 million children under the age of five were overweight.

Meanwhile, the Organisation for Economic Co-operation and Development (OECD) notes that obesity and being overweight increases the “risk of developing type 2 diabetes, cardiovascular diseases, fatty liver disease, certain forms of cancer, and dementia,” projecting that, by 2050, “there will be around 92 million premature deaths from obesity-related diseases in OECD, G20, and European Union (EU) countries.” In short, this is a global health crisis. If the numbers seem incredible, so too is the scale.

Debevoise & Plimpton LLP presented an overview of the impact of the Direct-To-Consumer (DTC) market – also referred to as ‘pharm-to-table’ – on patient access and investor strategy in an ever-changing regulatory landscape, together with the potential “political and legal risks.”

For example, minding that such platforms are “carefully structured to avoid implicating state and federal anti-kickback statutes, which have been the focus of a recent senatorial investigation and a lawsuit in Texas [in 2025].” This, as was brought against Eli Lilly in respect of its 2024-launched LillyDirect.

As the firm noted, pharma has long blamed high drug prices on the role of pharmacy benefit managers (PBMs), and the second Trump Administration’s Most-Favoured Nation (MFN) pricing set out to circumvent these ‘middlemen’, “thereby lowering prices for consumers.” Indeed, in Eli Lilly’s most recent earnings call, it was reported that “about one-fifth of total prescriptions for Zepbound are [now] attributable to cash-pay patients.”

What hasn’t been explicitly publicised is that, outside of these cash purchasers, those dependent on insurance coverage are not really going to benefit.

The BBC has reported that “an estimated 10% of Medicare beneficiaries will be eligible for expanded access to GLP-1 drugs, and will only pay $50.” The Medicare prices of Ozempic, Wegovy, Mounjaro, and Zepbound will be $245. However, it is worth noting that US federal law bans Medicare from covering GLP-1s drugs when used specifically for weight loss, and only 13 states provide coverage under Medicaid for weight loss purposes.

Furthermore, DTC platforms present ‘conflict-of-interest’ concerns. “Patients are more likely to request specific, brand-name drugs, which influences prescribing patterns in favour of expensive branded drugs that may not provide significant clinical benefit over more cost-effective alternatives,” explains the firm. It’s a statement supported by organisations like the American Medical Association.

Indeed, it is seemingly the cost and simplicity point that holds these GLP-1 options at the front of the race. After all, Rybelsus was the first oral GLP-1 – for diabetes – and garnered some $2.7 billion in sales for Novo Nordisk only last year. Ozempic, meanwhile, brought in near $14 billion. Same active ingredient, comparable efficacy evidenced in the clinical data, but the simplicity point seen with Eli Lilly’s pill is missing.

Rybelsus requires patients to undergo a strict fast to assist absorption through the stomach into the bloodstream (this process itself aided by the intestinal permeation enhancer salcaprozate sodium, aka SNAC, to achieve even a mere 1% absorption). Needless to say, adherence quickly becomes an issue.

Nevertheless, if we focus on the efficacy of orforglipron, as seen in the first of two Phase 3 ATTAIN-1 trials, the investigational oral glucagon-like peptide-1 (GLP-1) receptor agonist, at a dose of 36 mg, was seen to reduce weight by an average of 12.4% (27.3 lbs) compared to 0.9% with placebo at 72 weeks. This study had 3,127 adult participants with obesity, or who were overweight with a weight-related medical problem, and without diabetes.

Compared to oral Wegovy, which recently saw a ≥15% reduction in body weight in participants treated with an oral semaglutide 25 mg dose in the Phase 3 OASIS 4 trial at 71 weeks, such a number seems wanting. However, Lilly rides over that with improved cardiometabolic data.

The pharmaceutical industry is nothing if not a competitive arena, of course, and it is Novo Nordisk who is held in favour in terms of trust from physicians and payers, and practically speaking when it comes to scaled manufacturing. Add to this familiarity the reduced monthly price for Wegovy, and the maths seems solid.

If we look not too far back, when GLP-1s were an injectable-only option, this tussling between oral options seems incredible. But consumers are fussy. Mix into the pot emerging competitor oral GLP-1s from AstraZeneca, Roche, Pfizer, and Viking Therapeutics and Structure Therapeutics, and the menu option for consumers permits them – and their physicians – to be that bit more discerning.

The industry has turned to self-pay channels and even telehealth outfits to help market GLP-1s, also seeking to overcome ongoing coverage constraints around prescription obesity drugs, and fortify against compounding pharmacies when supply issues arose in the past. For instance, Novo’s oral Wegovy will be able to be purchased from around 70,000 US pharmacies (the starting dose, at least), including CVS and Costco, from select telehealth providers including Weight Watchers and GoodRx, and even the company’s own direct-to-patient sales channel, NovoCare Pharmacy, as well as TrumpRx (this latter, as part of an industry-wide move prompted by US Trump’s MFN drug pricing).

As Reuters reported, quite a few pharma companies are now set to sell drugs direct to patients in the US, including Eli Lilly, which, along with Novo, announced a deal with the Trump Administration that would “cut the prices of popular GLP-1 weight‑loss drugs for the government's Medicare and Medicaid [programmes]”, in addition to cash purchasers.

And so, if it wasn’t fully obvious yet: we find ourselves in the midst of a price war. As The Guardian reported, usually, “US list prices for weight-loss jabs are about $1,000 a month or more.” Similarly, CNN reported that list prices for GLP-1 drugs range “from around $1,000 to about $1,350,” but consumers with insurance coverage for the medicines typically pay much less.

Either which way, competition from Eli Lilly’s tirzepatide injectable options Mounjaro and Zepbound have kept Novo Nordisk’s share prices down, resulting in job losses and the appointment of new management and, meanwhile, Lilly’s orforglipron is said to have been planned to cap higher doses at $399 a month for cash-paying patients, in light of Novo’s announcement on the cash price of lower dose oral Wegovy (which the UK MHRA is still reviewing as we go to press).

However, the lower prices being touted by pharma – namely, the ‘duopoly’ of Novo and Lilly, which together account for an up to 85% share of the GLP-1 market – permit access for those with cash in hand, not the most socially and economically disadvantaged.

But, with a 70% adoption rate predicted to be able to “drive obesity rates down to 36.6% by 2035”, attaining that adoption rate necessitates dealing with access issues – especially given that, 65% of the time, failure to start GLP-1s is due to their prohibitive cost.

In short, the essential molecules are there; now, the infrastructure surrounding them needs addressing. That is to say, in addition to improved delivery technology and the potential of multi-agonist molecules, the ability to manufacture at scale and satisfy the needs of good, old-fashioned supply-and-demand – globally.

Novo Nordisk is, for example, looking to expand into Athlone, Ireland, to produce the Wegovy pill for markets beyond the US, the company’s CEO, Mike Doustdar, told Bloomberg. This, following successful blocking of compounder Hims & Hers from replicating oral semaglutide for the knockdown price of $49 per month. 

The manufacturing of GLP-1s involves a complex process that includes peptide synthesis, amino acid coupling, cleavage, purification, and chemical modifications. The solid-phase peptide synthesis (SPPS) method is the most common approach, where amino acids are added step-by-step to form a peptide chain anchored on a solid resin.

This process is followed by cleavage and purification to achieve the desired purity level. Additionally, chemical modifications such as PEGylation and lipidation are performed to improve the pharmacokinetic properties of the GLP-1 analogues.

According to Kelly Waldron at ValSource Inc, these drugs must abide by stringent regulatory standards, including Good Manufacturing Practices (GMP), which further increases the complexity and cost.

Furthermore, when manufactured using biologic cell culture processes, GLP‑1s require “15-20 intricate steps, including microbial fermentation and multi-stage purification,” which are error-prone. And while injectable forms of GLP-1s are subject to increased regulatory scrutiny to ensure sterility, they also require “2-8°C storage from production to patient delivery.”

So it is that, in emerging markets, “mishandling ruins up to 20% of shipments, forcing manufacturers to overproduce by about 25% to meet demand while compensating for anticipated product loss over the distribution chain.” Again, this produces a cost pain point. Waldron notes that “biosimilars of semaglutide are expected to enter markets like Canada and Brazil” this year, which will “intensify competition, pressure prices, and transform distribution models.”

As ever more consumers apprehend the slimming possibilities of these drugs, so the infrastructure that might enable wider access to GLP-1s – from manufacturing to policy – must expand to fit a truly global scale of appetite. And to realise the projected market figures discussed, that will yet require much greater investment.