The question driving metabolic drug development is no longer how much weight or glucose a therapy can lower. It is how long the benefit lasts, what patients lose along the way, and which diseases downstream of obesity can be modified as a result. That shift was evident throughout the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD 2026), where our team spent the week in the session halls and in conversation with investigators, clinicians and drug developers working at the forefront of the field.

Below, we look at the themes that stood out to us and what they mean for sponsors designing the next generation of cardiometabolic trials.

Maintenance and combination therapy take center stage

With highly effective incretin-based agents now established, attention is shifting from inducing weight loss to sustaining it. Sessions such as “Understanding and preventing weight regain after weight loss” and “Please don’t go: adherence and persistence to glucose-lowering medications” reflected a growing recognition that long-term durability is the real test of an obesity or diabetes therapy. A Lilly presentation on bimagrumab and semaglutide underscored the stakes: the cardiometabolic gains of weight loss reverse as weight returns after treatment stops.

Combination strategies were equally prominent. The program opened with a debate on early combination versus stepwise therapy, and multi-agonist and add-on approaches appeared throughout: retatrutide (TRIUMPH-2), survodutide (SYNCHRONIZE), amylin-based therapies, and a dedicated session on glucose-dependent insulinotropic polypeptide (GIP). Alongside these late-stage readouts, the volume of early-phase work on display was striking, a sign that the pipeline behind today’s leading assets remains deep and diverse. Oral small-molecule incretins designed for better gastrointestinal tolerability were a notable part of that pipeline.

For trial design, this means more studies with induction and maintenance phases, randomized withdrawal or dose-reduction arms, and longer follow-up to capture regain. It also means more factorial and add-on designs, where isolating each component’s contribution becomes a central statistical question.

Quality of weight loss: sarcopenia and muscle retention

How much weight a patient loses is no longer the only question; what they lose matters too. We saw noticeably more content on sarcopenia and lean mass this year, from mechanistic sessions on disrupted crosstalk between skeletal muscle and other organs to a dedicated session on preserving muscle during GLP-1 RA treatment, built around Regeneron’s trevogrumab COURAGE study.

COURAGE set the scene a year ago. In 26-week results presented at EASD 2025, roughly a third of semaglutide-induced weight loss came from lean mass, and adding the anti-myostatin antibody trevogrumab prevented about half of that loss. This year, Regeneron presented 52-week MRI data showing that trevogrumab prevented roughly 70% of the loss in fat-free muscle volume seen with GLP-1 RA treatment alone and preserved about 80% of contractile muscle, with favorable effects on muscle fat infiltration as well.

Antibodies are not the only approach. The PRESERVE trial tested a 12-week nutritional supplement program alongside weight loss and reported better muscle preservation, a greater share of weight lost as fat, and improvements in handgrip strength and six-minute walk distance. Several early-stage companies also presented compounds designed to drive fat loss while maintaining or even increasing muscle, either alone or in combination with incretins.

The open question now is whether preserved lean mass translates into preserved strength and function over the long term, particularly in older patients and those already at risk of frailty.

For sponsors, body composition is becoming a core endpoint rather than an exploratory one. That raises practical demands: standardized dual-energy X-ray absorptiometry (DXA) or magnetic resonance imaging (MRI) protocols across sites, validated functional measures such as grip strength and gait speed, and populations enriched for people in whom muscle loss carries real clinical consequences.

Clean data in obesity trials depends on knowing who is taking what

One of the most practical discussions of the week concerned compliance, prompted in part by a sponsor describing its own experience with protocol deviations and non-compliance at network sites. In obesity studies, adherence is hard to maintain, and “drop-ins” are a growing problem: participants on placebo, or on a study’s comparator arm, who start taking a commercially available weight-loss medication on the side. With GLP-1 RAs now widely accessible through prescription, compounding and online channels, this is no longer an edge case.

The consequence is a diluted treatment effect and data that are difficult to interpret. Self-reported concomitant medication use is not enough. Speakers argued for pharmacokinetic (PK) sampling built into the protocol, so that sponsors can detect off-study incretin exposure in placebo participants and confirm exposure in active arms.

This has direct implications for protocol and lab planning: bioanalytical assays that can detect marketed agents as well as the investigational product, sampling schedules that balance detection with participant burden, and pre-specified estimands and sensitivity analyses for handling drop-ins. Addressing this at the design stage is far cheaper than trying to explain an attenuated effect size after database lock.

From glucose control to disease modification, with hypertension next

Disease modification was a recurring theme, from a Delphi consensus on disease modification in type 2 diabetes to a session on barriers to using disease-modifying drugs in practice. Diabetes is where the case is being made first, but speakers were clear that hypertension and other obesity-driven conditions are next.

A presentation from Regor Therapeutics illustrated this well, highlighting effects on blood pressure and other cardiometabolic markers alongside weight loss. Late-stage data point in the same direction: in topline TRIUMPH-2 and TRIUMPH-3 results, Lilly reported reductions in systolic blood pressure, triglycerides, non-HDL cholesterol and hsCRP with retatrutide, alongside weight loss of up to 20.8% in people with type 2 diabetes.

One speaker made a pointed observation: the epidemiology has long told us that reducing obesity should reduce its downstream consequences, and now that we finally have therapies that reduce obesity at scale, the data are bearing that out. One proposed mechanism for the blood pressure effect is simple: eating fewer calories also means consuming less salt.

For sponsors, this opens the door to trials with blood pressure, renal or cardiovascular outcomes as primary endpoints, and to populations defined by comorbidity rather than by body mass index (BMI) or HbA1c alone. These studies demand rigorous measurement, such as ambulatory blood pressure monitoring, and careful handling of background antihypertensive changes during weight loss.

Who is enrolled matters too. Speakers noted that Asian patients account for roughly half of the global diabetes population, and South Asians in particular face both higher risk and higher barriers to treatment. Approaches developed largely in European and North American populations will not automatically translate, and trial populations should reflect where the disease burden actually sits.

Complications are back on the agenda, starting with the diabetic foot

While incretins dominated the headlines, some of the most clinically grounded content addressed complications. Diabetic foot disease featured in several presentations during the poster sessions, and the wider program included sessions on upper limb complications, cardiovascular autonomic neuropathy, diabetic kidney disease and post-transplant diabetes.

Diabetic foot disease remains one of the most costly and disabling consequences of diabetes, and therapeutic progress has been slow. Trials in this space bring their own challenges: heterogeneous wound populations, the need for blinded and standardized wound assessment, close coordination with podiatry and vascular teams, and endpoints such as complete wound closure or amputation that take time to accrue.

As metabolic therapies improve, there is a real opportunity to test whether they also change the trajectory of established complications, and to design dedicated studies for patients who are already living with them.

Looking ahead

EASD 2026 showed a field moving from proof of efficacy to proof of durable, whole-patient benefit. Maintenance strategies, muscle preservation, exposure verification and disease-modification endpoints all raise the bar for trial design and execution.

The sponsors who succeed will be those who build these considerations in from the start: PK sampling to protect data integrity, body composition and function measured with consistency, and endpoints that capture what happens to blood pressure, kidneys, feet and hearts, not only to the scale. The next generation of cardiometabolic therapies will be judged not only by how much weight patients lose, but by how well they live in the years that follow.