Though not quite as impressive as Moore’s law growth curve, the type 2 diabetes (T2D) and obesity (referred henceforth as T2DO) treatment market has seen exceptional growth in recent years.
Driven in part by the celebrity status of the glucagon-like peptide receptor agonist (GLP-1RA) treatments such as Ozempic, the T2DO sphere has received considerable investment, with new incretin treatments moving through the pipelines of various big and mid-sized pharma players.
This article provides a short preview of such treatments and the role of one gatekeeper in granting them passage onto the market – the National Institute for Health and Care Excellent, or NICE, for short.
Let’s start with a treatment that has been hitting the headlines for a while now: Semaglutide. Sold under the brand name Ozempic and Wegovy for T2D and obesity, respectively, Semaglutide is a GLP-1RA that works by activating incretin hormones found in the body, leading to a plethora of effects including an increased feeling of satiety.
Though the success of Semaglutide has been – and continues to be – monumental, the T2DO R and D train has already advanced. For example, Tirzepatide is a single molecule that activates both the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, with data from the SURMOUNT-2 trial reporting a 15.7% weight loss in people with overweight or obesity . Tirzepatide was approved for people with T2D in 2022 and obesity in 2023 under the brand names Mounjaro and Zepbound, respectively.
Tirzepatide is only the tip of the incretin iceberg, however, with several mid-sized pharma players moving dual treatments through their pipelines. Data from Carmot Therapeutics revealed their GLP-1/GIP treatment (CT-388) caused an eight per cent weight loss in just 4-weeks in people with obesity and T2D. Results also highlighted a dose dependent improvement in HOMA-IR, a measure of insulin sensitivity associated with T2D control.
Despite the perceived frostiness of the life sciences M&A market in 2023, Roche’s acquisition of Carmot Tx for $2.7 billion highlights big pharma’s continued interest in the T2DO space and appetite for acquiring mid-sized biotech’s with favourable Ph1/2 results. Next up is Altimmune’s treatment Pemvidutide, a dual GLP-1/glucagon dual receptor agonist currently being examined in the Ph2 MOMENTUM  and Ph2 IMPACT NASH trials . 48-week outcomes from the MOMENTUM trial revealed that Pemvidutide elicited a mean weight loss of 15.6 per cent and significant reductions in measures of cholesterol and triglycerides vs placebo.
While no significant improvements in HbA1c were observed, it is important to note this was not a primary endpoint nor focus of the trial. 12-week results from the Ph2 IMPACT NASH trial revealed a normalisation of liver fat in ~55 per cent of participants and meaningful weight-loss in the Pemvidutide arm.
Structure Therapeutics is another biotech with a single GLP-1RA and dual GLP-1/GIP treatment in its pipeline, though differentiated as their treatment is administered orally in tablet form. Results from its Ph1 trial in healthy participants revealed significant reductions in body weight vs placebo in non-obese persons , with trials in people with obesity and T2D due to commence this year.
The final nod in this short review must surely go to the big pharma company taking combinational treatments one step further again – Eli Lilly. Retatrutide is a triple-hormone-receptor agonist that activates the GLP-1, GIP, and glucagon receptors, and is currently being explored in Ph2/3 trials.
48-week results from the TRIUMPH Ph2 trial  reported a staggering mean weight reduction of up to 24.2 per cent in participants taking Retatrutide. Furthermore, those in the Retatrutide arm reported significant improvements in insulin sensitivity and significant reductions in liver fat content and HbA1c vs placebo, highlighting key improvements in metabolic health beyond weight loss alone.
With Retatrutide moving into Ph3 trials and Tirzepatide currently in various Ph3 trials to explore secondary indications such as cardiovascular outcomes, Eli Lilly is set to make significant advancements in the T2DO market.
Following approval, the aforementioned treatments ultimately make their way into governments, payors and in the hands of patients, but how? Here, I focus on the UK market and the role of NICE for granting access.
NICE was set up by the UK Government to provide advice, recommendations and ultimately the green light on which treatments are available on the NHS in England.
They do this by considering whether a new treatment will; 1) provide an essential benefit to patients; 2) support the NHS in meeting its public health targets (for example, a reduction in obesity); and, of course, 3) whether the treatment is cost effective.
Based on such criteria, NICE will choose one of 5 outcomes ranging from ‘recommended – the medicine should be routinely available’ to ‘not recommended – the medicine should not be available’; with ‘optimised – the medicine is only available for certain people with a condition’ falling somewhere between the two.
A full review of how NICE come to such decision is beyond the scope of this short review and the inclined reader should instead see nice.org.uk. Instead, I will focus on how treatments are ranked and approved depending on cost effectiveness.
To measure the cost effectiveness of a new treatment, NICE assesses it on three focal issues: 1) is a service or intervention effective (that is, does it achieve what it sets out to achieve); 2) is it more effective than the alternatives and, if so, by how much; and 3) how much does it cost compared with the next best alternative.
Taking these issues it account, NICE then considers one’s quality of life and the length of life they will gain as a result of receiving such treatment, resulting in a metric called ‘quality-adjusted life years (QALYs)’.
Treatments are then generally considered cost effective and therefore recommended for use in the UK if for each QALY gained they cost the NHS less than £20,000, with those costing between £20,000-£30,000 also potentially meeting the standard.
For example, NICE estimated the cost of Semaglutide for overweight and obesity at £600 per QALY gained , therefore deeming it cost effective compared with liraglutide and, amongst other factors, recommending its approval in England.
Tirzepatide soon followed, with various estimated scenario analyses against all comparators coming in at less than £20,000 per QALY gained and NICE therefore deeming it cost effective for T2D treatment and management .
With the rates of T2D and obesity surging, and the strain on NHS resources forever edging higher, cost effectiveness is likely to command a greater influence when approving the emerging treatments explored in this review.
The improvements in metabolic health emerging from T2DO trials is testament to the scientific advancements in this space and the burgeoning interest in treating these historically labelled ‘lifelong’ diseases.
Furthermore, the advent of AI-enabled drug discovery platforms for opening new frontiers of treatment classes could allow big pharma to curtail growing R and D costs, ultimately lowering the final bill passed on to payers and patients alike.
To conclude, incretin-based treatments have already made a huge positive impact for improving metabolic health, but by judging what is coming through the various pipelines of big and mid-sized pharma, the future of T2DO treatments is set to be brighter and healthier than ever before.
 Garvey, W.T., Frias, J.P., Jastreboff, A.M., le Roux, C.W., Sattar, N., Aizenberg, D., Mao, H., Zhang, S., Ahmad, N.N., Bunck, M.C. and Benabbad, I., 2023. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet.
 Rosenstock, J., Frias, J., Jastreboff, A.M., Du, Y., Lou, J., Gurbuz, S., Thomas, M.K., Hartman, M.L., Haupt, A., Milicevic, Z. and Coskun, T., 2023. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. The Lancet.