IPM Take
The GLP-1 race is starting to look less like a contest for the single most powerful weight-loss drug and more like an attempt to build a treatment architecture.
At EASD 2026, Lilly will present data spanning an oral GLP-1, the established dual agonist tirzepatide, the investigational triple agonist retatrutide and a combination pairing tirzepatide with the selective amylin receptor agonist eloralintide.
That breadth matters because patients with obesity and type 2 diabetes do not need the same thing. Some may prioritise an oral medicine. Others may need greater weight reduction, cardiovascular-risk management, stronger glycaemic control or treatment that addresses additional complications.
The emerging precision-medicine question is therefore changing. It is no longer simply, does an incretin work?
It is becoming, which mechanism, intensity and delivery model creates the most value for which patient?
That could make treatment more personalised. It could also make reimbursement considerably more complicated.
Executive Summary
Lilly plans to present new cardiometabolic data at the European Association for the Study of Diabetes annual meeting in Milan from 28 September to 2 October 2026. Its programme includes retatrutide, tirzepatide, Foundayo (orforglipron) and eloraTZP.
In TRIUMPH-2, adults with obesity or overweight and type 2 diabetes receiving the highest studied retatrutide dose lost an average 20.8% of body weight at 80 weeks, or 22.5 kg, while A1C fell by up to 1.6 percentage points. Retatrutide activates GIP, GLP-1 and glucagon receptors and remains investigational. Lilly has said it plans to submit the drug to the FDA in the first quarter of 2027.
Foundayo, the small-molecule oral GLP-1 orforglipron, is already FDA-approved in the United States for chronic weight management. Its type 2 diabetes programme remains separate. In ACHIEVE-4, Foundayo met the cardiovascular safety objective of non-inferiority to insulin glargine. The reported hazard ratios numerically favoured Foundayo for MACE-4 and MACE-3, but the confidence intervals crossed 1, so these results should not be interpreted as proof of cardiovascular superiority.
Lilly will also present Phase 2 results for eloraTZP, which combines tirzepatide with eloralintide, a selective amylin receptor agonist. Earlier Phase 1 data reported approximately 17% weight loss over 16 weeks with eloralintide 3 mg plus tirzepatide 5 mg, compared with 10% with tirzepatide 5 mg alone. The forthcoming Phase 2 results will be important because the more mature comparative evidence is not yet public.
Meanwhile, tirzepatide itself has moved beyond glucose and weight endpoints. The FDA approved Mounjaro in August 2026 to reduce major cardiovascular events in adults with type 2 diabetes at high cardiovascular risk, based on SURPASS-CVOT.
Why it matters
- HTA bodies: A wider range of mechanisms will make simple drug-versus-placebo assessment increasingly inadequate. Relative value may depend on cardiovascular risk, diabetes status, magnitude of weight loss, route of administration, durability and whether combinations deliver clinically meaningful gains beyond established therapies.
- Payers: More therapeutic choice could support personalised treatment, but combination therapy and increasingly potent agents may increase costs. Reimbursement systems may need to define sequencing rules rather than treating all incretin-based medicines as interchangeable.
- Industry / innovation partners: Lilly’s portfolio shows where competitive differentiation is moving. The next advantage may come not from another GLP-1 alone, but from combinations, additional hormonal pathways and products designed for distinct treatment preferences or cardiometabolic phenotypes.
The first phase of the obesity-drug revolution was about proving that pharmacological treatment could deliver weight loss previously considered difficult to achieve without surgery.
The next phase may be about choice.
Lilly’s EASD 2026 programme illustrates that shift unusually clearly. Rather than placing the future of its cardiometabolic franchise behind one successor to tirzepatide, the company is developing several approaches with different mechanisms, formulations and potential roles.
Foundayo represents one end of that spectrum. It is a once-daily, small-molecule oral GLP-1 receptor agonist that can be taken without food or water restrictions. The FDA approved it for chronic weight management in April 2026. For patients reluctant to inject a medicine or health systems seeking a simpler oral option, route of administration may itself become part of treatment selection.
Retatrutide moves in the other direction, toward greater hormonal complexity.
The drug activates three receptors, GIP, GLP-1 and glucagon. In TRIUMPH-2, participants with type 2 diabetes and obesity or overweight lost up to 20.8% of their body weight at 80 weeks. That is particularly notable because weight reduction is often smaller in people with type 2 diabetes than in comparable obesity trials without diabetes.
But a larger percentage on the scale is not automatically a better treatment for every patient.
Greater potency has to be balanced against tolerability, discontinuation, cost, long-term safety, cardiovascular and renal outcomes, and whether the additional weight loss produces proportional gains in health and quality of life.
The pipeline is moving beyond GLP-1 alone
EloraTZP pushes the strategy further.
Rather than adding another incretin receptor to a single molecule, Lilly is combining tirzepatide with eloralintide, which targets the amylin receptor. Amylin biology is attractive because of its role in satiety and energy intake, but the value of the combination will depend on whether it produces enough additional benefit to justify two mechanisms rather than one.
Early Phase 1 data are provocative, with 17% weight loss over 16 weeks reported for the combination versus 10% for tirzepatide 5 mg alone. However, Phase 1 results are not enough to establish comparative clinical value. The upcoming Phase 2 data will therefore matter considerably more.
Foundayo raises a different question: how much efficacy is enough when convenience improves?
Its oral formulation may deliver less weight loss than the most potent injectable programmes, but that comparison misses part of the point. A drug that patients can start, tolerate and continue may create more real-world value than a theoretically stronger medicine that is difficult to access or sustain.
That is where personalised cardiometabolic medicine becomes less about molecular elegance and more about treatment matching.
One patient may need maximum weight reduction. Another may prioritise avoiding injections. Another may have established cardiovascular disease. Another may primarily need glycaemic control. Future treatment choices may also incorporate lean-mass preservation, liver disease, kidney disease, sleep apnoea or response to previous therapies.
Lilly’s portfolio suggests industry is preparing for that segmentation before health systems have decided how to pay for it.
And that may become the real policy problem.
If multiple effective medicines exist across different mechanisms and levels of intensity, reimbursement cannot simply ask whether each drug works.
It will have to ask who needs which one, in what sequence, and at what price.
That is a much more difficult question than deciding which drug produces the largest weight-loss percentage.
