EASD 2026 Obesity Medicine Roundup: A Comprehensive Review of the New Data

ABBV-295 is an investigational amylin-based treatment being developed for chronic weight management.

The Phase 1 study evaluated weekly, every-other-week, and monthly dosing. ABBV-295 demonstrated an approximately 11- to 12-day half-life, supporting continued investigation of dosing intervals longer than once weekly.

Over 12 to 13 weeks, least-squares mean weight reductions ranged from 7.8% to 9.8% with weekly regimens, 9.7% with every-other-week dosing, and 7.9% with monthly dosing, compared with approximately 0.3% with placebo.

GI adverse events were predominantly mild. Nausea occurred in 33.3% of participants receiving ABBV-295 and diarrhea in 20%. GI-related discontinuation occurred in 4.4%.

The study remains early. The detailed multiple-dose analysis included 60 participants, 88% of whom were male, and treatment lasted only 12 to 13 weeks. AbbVie plans to advance ABBV-295 into Phase 2 development.

Ascletis presented new preclinical data on a fixed-dose combination of ASC36, an amylin receptor agonist, and ASC35, a GLP-1/GIP receptor agonist.

The formulation is being developed with the goal of once-monthly to potentially once-quarterly injection.

In diet-induced-obesity animal models, the combination produced substantial weight reduction and was compared with other amylin/incretin combinations. These are animal data and cannot establish comparative efficacy in humans.

The main significance at this stage is the dosing concept and combination strategy. A Phase 1 study of oral ASC36 has begun. Human safety, pharmacokinetics, and weight-loss data for the fixed-dose combination remain important next steps.

The Phase 3 SYNCHRONIZE-2 trial evaluated survodutide in adults with obesity or overweight and type 2 diabetes.

At 76 weeks, survodutide produced up to 13.1% mean weight loss using the efficacy estimand, compared with 3.1% with placebo. Up to 79.3% of participants achieved at least 5% weight loss, compared with 32.7% receiving placebo.

A1C decreased by up to 1.21 percentage points from a baseline of 7.4%, compared with 0.03 points with placebo. Waist circumference decreased by 11.1 cm versus 3.5 cm, with additional improvements reported in fasting glucose and measures of insulin sensitivity.

The tolerability findings are also important. Gastrointestinal events were the most common adverse events and were generally mild to moderate. GI-related treatment discontinuation occurred in 18% of survodutide-treated participants versus 1.2% with placebo.

Results were presented at EASD and simultaneously published in The New England Journal of Medicine. Additional body-composition findings from the SYNCHRONIZE program also showed that adipose-tissue reduction accounted for the majority of tissue lost.

Survodutide remains in a broad late-stage development program spanning obesity and related metabolic disease.

EASD included an indirect treatment comparison using data from SURMOUNT-1 and STEP UP to compare tirzepatide with semaglutide 7.2 mg.

Under the treatment-regimen analysis, tirzepatide 15 mg was associated with approximately 4.5 percentage points greater estimated weight reduction than semaglutide 7.2 mg.

This was not a randomized head-to-head clinical trial. Participants came from separate studies, and differences in populations, study design, and statistical assumptions remain important. The estimated difference was smaller under the efficacy estimand and did not reach statistical significance.

EASD also included cardiovascular data from SURPASS-CVOT in people with type 2 diabetes and established cardiovascular disease. Tirzepatide was noninferior to dulaglutide for MACE-3, with a hazard ratio of 0.92 and 95.3% confidence interval of 0.83 to 1.01, while producing greater reductions in A1C and body weight.

Several orforglipron analyses were presented at EASD.

The Phase 3 ACHIEVE-4 trial compared orforglipron with insulin glargine in adults with type 2 diabetes and overweight or obesity who were at increased cardiovascular risk.

For the primary cardiovascular endpoint, MACE-4, the hazard ratio was 0.84 with a 95% confidence interval of 0.59 to 1.20, meeting the prespecified criterion for cardiovascular noninferiority. For MACE-3, the hazard ratio was 0.77 with a 95% confidence interval of 0.52 to 1.13.

These findings establish noninferiority for cardiovascular safety. Because the confidence intervals for MACE-3 and MACE-4 crossed 1.0, they should not be described as proof that orforglipron reduces cardiovascular events compared with insulin glargine.

At 52 weeks, using the efficacy estimand, A1C decreased 1.6 percentage points with orforglipron versus 1.0 point with insulin glargine. Body weight decreased 8.8% with orforglipron while increasing 1.7% with insulin glargine.

Additional improvements included reductions in waist circumference, systolic blood pressure, triglycerides, non-HDL cholesterol, and hsCRP.

A separate ATTAIN-1 post-hoc analysis used validated prediction models to estimate future cardiometabolic risk. The highest orforglipron dose was associated with a 57% lower predicted 10-year risk of developing type 2 diabetes and an 18% lower predicted cardiovascular-disease risk versus placebo. These are modeled risk estimates, not observed reductions in clinical events.

Additional EASD analyses evaluated appetite, response to the food environment, physical and psychosocial functioning, insulin sensitivity, and beta-cell function.

The Phase 3 TRIUMPH-2 trial provided detailed results for retatrutide in adults with obesity or overweight and type 2 diabetes.

At 80 weeks, mean weight loss using the efficacy estimand was:

• 12.7% with 4 mg
• 19.1% with 9 mg
• 20.8% with 12 mg
• 4.0% with placebo

Participants receiving 12 mg lost an average of approximately 49.6 pounds. Among participants beginning with a BMI of at least 35 kg/m², mean weight loss reached 23.4% with the 12 mg dose.

A1C decreased by up to 1.6 percentage points across the active doses, and as many as 40% of participants reached an A1C below 5.7%. At 12 mg, 59.5% of participants no longer met BMI criteria for obesity at the end of the study.

The most common adverse events were gastrointestinal and generally mild to moderate. Treatment discontinuation because of adverse events ranged from 3.8% to 11.6% across the retatrutide doses, compared with 4.9% with placebo.

TRIUMPH-2 was presented at EASD and simultaneously published in The Lancet.

A Phase 2b study evaluated eloralintide combined with tirzepatide in 367 adults with obesity or overweight and type 2 diabetes.

At 48 weeks, the highest-dose combination, eloralintide 9 mg plus tirzepatide 15 mg, produced 23.3% mean weight loss using the efficacy estimand, or approximately 54 pounds.

Tirzepatide 15 mg alone produced 14.8% mean weight loss.

A1C decreased by as much as 2.9 percentage points with combination therapy, compared with 2.4 points with tirzepatide 15 mg alone.

Eloralintide monotherapy produced up to 12.3% mean weight loss.

Gastrointestinal adverse events were common, particularly during dose escalation. Discontinuation because of adverse events ranged from 10.8% to 27.0% across the combination groups, compared with 2.9% with tirzepatide alone.

Lilly plans to advance the combination into Phase 3 using an optimized titration approach.

Additional findings from the BELIEVE withdrawal extension examined what happened to body composition and cardiometabolic measures after bimagrumab, semaglutide, or combination treatment was stopped.

The broader BELIEVE program has focused on whether muscle-directed therapy can change the composition of weight loss by producing greater reductions in adipose tissue while preserving or increasing lean tissue.

The EASD extension provided additional information about durability after treatment withdrawal rather than establishing a new peak weight-loss result.

This program is part of a broader shift toward studying not only how much weight is lost, but what type of tissue accounts for that loss.

Olatorepatide was presented as a late-breaking Phase 3 update on the final day of EASD.

The Phase 3 LIGHTEN study included 604 adults with obesity or overweight in China and compared once-weekly olatorepatide 5 mg, 10 mg, and 15 mg with placebo for 48 weeks.

At 15 mg, mean weight loss reached 19.3% at week 48. The weight curve had not clearly plateaued.

With the 15 mg dose:

• 95.2% achieved at least 5% weight loss
• 88.9% achieved at least 10%
• 71.7% achieved at least 15%

Mean waist circumference decreased 16.0 cm with 15 mg versus 3.6 cm with placebo.

Across olatorepatide treatment groups, nausea was reported in 7.8%, vomiting in 4.9%, diarrhea in 16.9%, and constipation in 5.1%. The sponsor reported no discontinuations or early withdrawals because of treatment-related adverse events.

Cross-trial safety comparisons should be interpreted cautiously because adverse-event reporting and study populations differ between trials.

Olatorepatide is administered once weekly. Its Chinese application for chronic weight management is under regulatory review, while Regeneron holds development and commercialization rights outside mainland China, Hong Kong, and Macau.

EASD included three mazdutide presentations spanning reproductive health, adipose-tissue biology, and liver disease.

The most clinically relevant new human analysis came from GLORY-2 and included 284 reproductive-age women with obesity.

Mazdutide 9 mg was associated with improvements in menstrual regularity and insulin resistance over 60 weeks. In the overall reproductive-age subgroup, HOMA2-IR decreased 41.1% from baseline, compared with a 1.4% increase with placebo.

Analyses were also performed in women with oligomenorrhea, irregular menstrual cycles, and physician-diagnosed PCOS.

These were subgroup findings and do not establish mazdutide as a treatment for PCOS itself.

For context, the primary GLORY-2 trial previously reported 18.55% mean weight loss with mazdutide 9 mg versus 3.02% with placebo at 60 weeks using the efficacy estimand.

Two additional EASD studies explored adipose thermogenesis and liver/MASH mechanisms. Those studies were preclinical and should be interpreted separately from the Phase 3 human results.

Ribupatide is advancing through Kailera's global Phase 3 obesity program.

A Phase 1 crossover study presented at EASD included 51 adults with overweight or obesity and evaluated whether injection location changed drug exposure.

Drug exposure was similar whether ribupatide was administered in the abdomen, thigh, or upper arm, supporting all three as potential injection sites.

Hengrui also presented a Phase 2 study of ribupatide in adults with obesity and polyendocrine metabolic ovarian syndrome. Previously reported results from that study showed up to 21.2% mean weight loss at 32 weeks using the efficacy estimand, along with improvements in menstrual-cycle frequency.

The reproductive findings require confirmation in larger studies.

Hengrui presented Phase 3 results from OUTSTAND-1 and OUTSTAND-2 in type 2 diabetes.

These presentations expand the clinical safety and efficacy database for safiglipron but were primarily diabetes studies rather than new pivotal obesity trials.

Safiglipron remains part of Kailera's global oral obesity program, with obesity-specific development continuing.

The first-in-human Phase 1 program provided an early look at KAI-4729.

After 12 weeks, participants receiving 12 mg once weekly achieved 16.0% mean weight loss and a 67.3% mean reduction in liver fat content.

Ribupatide 4 mg was included as an active-control arm and produced 16.7% mean weight loss and a 38.4% reduction in liver fat.

The sample size is a major limitation. Only 10 participants received KAI-4729 12 mg and 10 received ribupatide 4 mg, so these results should not be used to infer comparative efficacy between the molecules.

Most treatment-emergent adverse events were mild to moderate and gastrointestinal.

Kailera plans additional clinical development outside China.

MTRX31 is being studied through a different mechanism than appetite-focused incretin therapies.

MitoRx is studying whether modifying mitochondrial metabolism can improve metabolic flexibility and shift the balance between fat and carbohydrate oxidation.

In diet-induced-obesity mice, MTRX31 restored liver mitochondrial density toward levels observed in lean-control animals, reduced lipid droplets, and increased glycogen flexibility.

These findings remain preclinical. Whether this mechanism produces meaningful weight loss, body-composition effects, or metabolic benefits in humans remains unknown.

Several semaglutide studies addressed outcomes beyond conventional weight-loss efficacy.

COMPETE SWITCH CV: cardiovascular outcomes after treatment intensification

Announced September 29, this retrospective US claims analysis compared adults with type 2 diabetes who increased weekly semaglutide from 1 mg to 2 mg with those who switched to tirzepatide. The cardiovascular comparison included 185,705 dose escalators and 23,104 switchers, within a broader treatment-pattern cohort of 636,525 people.

Switching was associated with a higher risk of the composite of all-cause death, heart attack, or stroke than dose escalation (adjusted hazard ratio 1.06; 95% CI 1.04–1.08). Novo described this as approximately 6% lower relative risk with semaglutide escalation. This is a relative association, not a six-percentage-point absolute reduction.

Treatment was not randomized; residual confounding and differences in treatment selection may explain part of the association. Tirzepatide doses varied, and about 31% reached at least 10 mg. These results do not prove that semaglutide is cardiovascularly superior or apply directly to obesity treatment without diabetes.

A post-hoc MRI analysis from STEP UP included 55 adults with obesity without diabetes. In pooled semaglutide 2.4 mg and 7.2 mg groups, mean liver fat decreased from 8.8% to 3.1% at week 72.

Among the 26 participants whose liver fat exceeded 5% at baseline, 23 of 26, or 88.5%, reached a liver-fat level below 5%.

This was a small post-hoc analysis with pooled doses and should be interpreted accordingly.

The OCTANE real-world analysis evaluated people switching from injectable semaglutide or tirzepatide to oral semaglutide for weight management. Among those who stayed on treatment for three months, participants lost another 4.1% of body weight on average over three months, and 40.7% achieved at least 5% additional weight reduction.

OCTANE used de-identified telehealth data without a randomized comparator, so it provides real-world information rather than evidence that switching is superior to remaining on injectable therapy.

Novo Nordisk presented several analyses examining effects of cagrilintide plus semaglutide beyond the number on the scale.

A 52-week functional MRI study evaluated adults with overweight or obesity. Treatment altered responses to high-calorie food cues in brain areas involved in reward, cravings, sensory processing, and behavioral control. Participants also reported improvements in hunger, cravings, appetite, and food-related thoughts.

In that study, the estimated treatment difference in body weight was 22.4 percentage points versus placebo at 52 weeks.

Separate REIMAGINE 1 data in adults with early type 2 diabetes showed reductions in abdominal fat as well as liver and pancreatic fat, alongside 14.3% weight loss at week 40.

A REIMAGINE 2 post-hoc analysis evaluated markers of bone remodeling. The early biomarker findings were described as reassuring despite substantial weight loss, but they should not be interpreted as evidence about long-term fracture risk.

Additional EASD analyses included continuous-glucose-monitoring outcomes, body composition, achievement of combined A1C and weight targets, and the relationship between achieved dose and weight reduction.

Cagrilintide was also evaluated independently from combination therapy.

An EASD analysis from REDEFINE 1 examined patient-reported physical functioning with cagrilintide 2.4 mg.

The findings add to the characterization of cagrilintide as a standalone amylin treatment but did not represent a new primary Phase 3 weight-loss readout.

Zenagamtide was featured as part of Novo Nordisk's broader discussion of amylin biology and next-generation obesity treatment.

EASD did not include a new headline human obesity efficacy readout for zenagamtide comparable with previously reported clinical data.

The EASD update therefore focused mainly on the program’s scientific and mechanistic context.

EASD included Phase 2 presentations involving UBT251 in obesity and type 2 diabetes.

The program had already generated substantial Phase 2 weight-loss findings before the meeting. EASD further characterized the molecule but did not introduce a separate new pivotal obesity efficacy result comparable with the larger late-stage readouts discussed above.

UBT251 remains part of Novo Nordisk's expanding next-generation obesity pipeline through its relationship with United Biotechnology.

The COURAGE trial examined whether adding trevogrumab could preserve lean tissue during semaglutide-associated weight loss.

With semaglutide alone, DXA-measured lean mass decreased 7.3% at 52 weeks.

Adding trevogrumab 75 mg reduced that decline to 4.2%, representing 42.5% relative preservation of DXA-measured lean mass.

MRI provided a more muscle-specific measure. At week 52:

• Trevogrumab 25 mg preserved 71.8% of the thigh-muscle volume that otherwise would have been lost with semaglutide.
• Trevogrumab 75 mg preserved 68.9%.

The lower trevogrumab doses did not meaningfully increase total weight loss beyond semaglutide. The potential role being studied is therefore changing the composition of weight loss rather than simply increasing the amount of weight lost.

A prespecified analysis also found that participants beginning the trial with low lean mass lost more lean tissue with semaglutide alone and showed numerically greater preservation when trevogrumab was added.

The results were presented at EASD and are in press at The Lancet. Regeneron plans additional research in older adults with obesity and reduced muscle mass or strength.

EASD included results from the 36-week COMO-1 obesity study and a related blood-pressure analysis.

The presentations described clinically meaningful weight reduction together with blood-pressure lowering and no apparent increase in resting heart rate.

COMO-1 randomized 268 participants with obesity or overweight without type 2 diabetes.

The EASD abstract reports a post-hoc analysis of 171 protocol-compliant participants whose adherence was checked using drug levels. These selected analyses should not be treated as results from the full randomized trial population.

RGT-075 remains in Phase 2 development as an oral small-molecule GLP-1 receptor agonist.

EASD presented the full 48-week Phase 2 obesity study along with analyses examining visceral adiposity and other cardiometabolic measures.

The topline obesity findings had been announced earlier in 2026. At the highest 24 mg dose, enicepatide produced 22.5% placebo-adjusted weight loss at 48 weeks using the efficacy estimand, without an apparent weight-loss plateau.

Using the treatment-regimen estimand, placebo-adjusted weight loss was 18.3%.

At week 48, 54% of participants receiving 24 mg had a BMI below 30 kg/m² compared with 13% receiving placebo.

Most GI adverse events were mild to moderate. Treatment discontinuation because of adverse events occurred in 5.9% across enicepatide groups versus 1.3% with placebo.

Phase 3 obesity development is underway.

Roche also presented studies of acmopatide in people with type 1 diabetes and overweight or obesity.

This is a distinct population because obesity treatment in type 1 diabetes requires consideration of insulin use, hypoglycemia risk, glycemic variability, and weight.

The EASD program included body-weight and body-composition findings as well as mechanistic analyses involving glucose appearance and insulin sensitivity.

This remains a specialized clinical-development program rather than a general Phase 3 obesity program.

Roche presented early Phase 1 data from a four-week study in adults with overweight or obesity and type 2 diabetes.

The study focused primarily on safety, tolerability, pharmacokinetics, and early pharmacodynamic effects.

Because treatment lasted only four weeks, these findings should be viewed as early development data rather than an estimate of CT-996's eventual weight-loss efficacy.

Full results from the Phase 2 ZUPREME-1 study were published in The Lancet Diabetes & Endocrinology and presented at EASD.

The randomized study included 485 participants in the primary analysis.

At week 42, petrelintide produced up to 10.7% mean weight loss versus 1.7% with placebo using the efficacy estimand.

Using the treatment-policy estimand, weight reduction reached 10.2% versus 1.4%.

The tolerability findings were notable. GI events were generally mild and occurred at rates described as similar to placebo. At the maximally effective dose, there were no reported vomiting events and no treatment discontinuations because of GI adverse events.

Other findings included:

• Waist circumference reduction of up to 10.8 cm
• hsCRP reduction of up to 41%
• Triglyceride reduction of up to 21%
• Pulse-rate reduction of up to 2.9 beats per minute

A global Phase 3 registration program is underway.

A late-breaking Phase 1b study evaluated ecnoglutide in 48 adolescents ages 12 to 17 with obesity.

After 20 weeks, BMI decreased approximately 11.2% to 12.6% across active-treatment groups, with body-weight reductions of approximately 10.4% to 12.1%.

The placebo group gained approximately 1.2% body weight.

No drug-related serious adverse events were reported, and gastrointestinal events were generally described as mild and transient.

The major limitations are the small sample size, short duration, and single-country population.

A Phase 3 adolescent obesity program is underway.

Verdiva presented receptor-pharmacology data on VRB-103, an oral amylin candidate designed with the potential for once-weekly administration.

In laboratory testing, VRB-103 demonstrated activity across the three human amylin receptor subtypes with relative selectivity compared with the calcitonin receptor.

The company also performed in-vitro comparisons with other investigational amylin therapies.

These receptor-level experiments do not establish superior clinical efficacy or tolerability.

VRB-103 has entered Phase 1 human testing both as monotherapy and in combination with Verdiva's oral GLP-1 candidate VRB-101.

The concept is notable because it combines two areas of active obesity research: amylin biology and potentially once-weekly oral therapy.