Across 67 European CTIS-authorized Phase II and Phase III obesity/overweight trials, body-weight change was the dominant endpoint signal, appearing in 41/67 trials (61.2%) and serving as a primary endpoint in 36/67 trials (53.7%). The secondary endpoint layer was broader and cardiometabolic: blood pressure and glycaemic endpoints appeared in 28/67 trials each (41.8%), while waist/hip anthropometry, safety/tolerability, and patient-reported quality-of-life/function endpoints each appeared in 27/67 trials (40.3%). Phase III trials made up 58/67 trials (86.6%), and median time from initial CTIS submission to first authorization was 102 days.
Body-weight change was the leading endpoint category, measured in 41/67 trials (61.2%). The next most frequent categories were glycaemic/diabetes markers and blood pressure/vital signs, each in 28/67 trials (41.8%), followed by waist/hip anthropometry, safety/tolerability, and patient-reported quality-of-life or function endpoints, each in 27/67 trials (40.3%).
European obesity trial endpoint design is not only weight-centric. Body weight is the common anchor, but the repeat appearance of glycaemic, blood-pressure, waist/hip, safety, and patient-reported endpoints shows that most competitive CTIS submissions position obesity therapies as cardiometabolic and functional interventions, not only weight-loss products.
Primary endpoints were concentrated around body-weight change: 36/67 trials (53.7%) used it as a primary category, while categorical weight-loss thresholds and BMI/BMI SDS each appeared as primary categories in 6/67 trials (9.0%). Secondary endpoints carried most of the broader clinical burden: body weight appeared secondarily in 30/67 trials (44.8%), blood pressure in 28/67 (41.8%), waist/hip and quality-of-life/function in 27/67 each (40.3%), glycaemic markers in 26/67 (38.8%), and safety/tolerability in 25/67 (37.3%).
| Endpoint category | Primary | Secondary | Exploratory / other |
|---|---|---|---|
| Body weight change | 36/67 · 53.7% | 30/67 · 44.8% | 0/67 · 0.0% |
| Categorical weight-loss thresholds | 6/67 · 9.0% | 13/67 · 19.4% | 0/67 · 0.0% |
| BMI / BMI SDS | 6/67 · 9.0% | 19/67 · 28.4% | 0/67 · 0.0% |
| Renal / kidney | 4/67 · 6.0% | 5/67 · 7.5% | 0/67 · 0.0% |
| Musculoskeletal pain/function | 4/67 · 6.0% | 5/67 · 7.5% | 0/67 · 0.0% |
| Glycaemic / diabetes markers | 3/67 · 4.5% | 26/67 · 38.8% | 0/67 · 0.0% |
| Safety / tolerability | 2/67 · 3.0% | 25/67 · 37.3% | 0/67 · 0.0% |
| Blood pressure / vital signs | 1/67 · 1.5% | 28/67 · 41.8% | 1/67 · 1.5% |
| Waist / hip anthropometry | 0/67 · 0.0% | 27/67 · 40.3% | 0/67 · 0.0% |
| PRO / quality of life | 0/67 · 0.0% | 27/67 · 40.3% | 0/67 · 0.0% |
| Lipids / cardiometabolic risk | 0/67 · 0.0% | 23/67 · 34.3% | 0/67 · 0.0% |
| PK / immunogenicity | 0/67 · 0.0% | 8/67 · 11.9% | 0/67 · 0.0% |
The primary endpoint strategy is narrow and efficacy-led, while the secondary endpoint strategy is broad and differentiation-led. For CTIS/EU submissions, this means the main estimand usually remains weight or BMI, but the evidence package increasingly needs cardiometabolic, anthropometric, safety, and patient-function support.
Phase II trials were fewer (9/67; 13.4%) and showed a mixed exploratory-development profile: body weight, safety/tolerability, and glycaemic markers each appeared in 5/9 trials (55.6%), while categorical weight-loss thresholds and DXA/MRI body-composition endpoints each appeared in 4/9 trials (44.4%). Phase III trials dominated the dataset (58/67; 86.6%) and were more standardized around body weight (36/58; 62.1%), blood pressure (25/58; 43.1%), waist/hip and quality-of-life/function endpoints (24/58 each; 41.4%), glycaemic markers (23/58; 39.7%), and safety/tolerability (22/58; 37.9%).
| Endpoint category, any role | Phase II | Phase III |
|---|---|---|
| Body weight change | 5/9 · 55.6% | 36/58 · 62.1% |
| Safety / tolerability | 5/9 · 55.6% | 22/58 · 37.9% |
| Glycaemic / diabetes markers | 5/9 · 55.6% | 23/58 · 39.7% |
| Categorical weight-loss thresholds | 4/9 · 44.4% | 11/58 · 19.0% |
| Body composition / DXA-MRI | 4/9 · 44.4% | 3/58 · 5.2% |
| Blood pressure / vital signs | 3/9 · 33.3% | 25/58 · 43.1% |
| Waist / hip anthropometry | 3/9 · 33.3% | 24/58 · 41.4% |
| PRO / quality of life | 3/9 · 33.3% | 24/58 · 41.4% |
| BMI / BMI SDS | 1/9 · 11.1% | 20/58 · 34.5% |
| Renal / kidney | 2/9 · 22.2% | 6/58 · 10.3% |
| Musculoskeletal pain/function | 1/9 · 11.1% | 5/58 · 8.6% |
Phase II obesity trials use endpoint breadth to explore mechanism, safety, dose, and body composition. Phase III submissions converge toward a repeatable weight-plus-cardiometabolic package, with BMI becoming more visible in confirmatory and pediatric settings.
The largest segment was general obesity/overweight without a named major comorbidity (34/67; 50.7%). Diabetes/prediabetes-enriched trials were the second-largest group (14/67; 20.9%) and had the strongest body-weight plus glycaemic pattern: 12/14 (85.7%) measured body weight in any hierarchy and 11/14 (78.6%) measured glycaemic endpoints. Cardiorenal, blood-pressure, or obstructive sleep apnea enriched trials represented 7/67 trials (10.4%) and were less anchored in primary body weight (1/7; 14.3%).
| Disease / enrichment group | Trials | Primary body weight | Any body weight | Most distinct co-endpoint |
|---|---|---|---|---|
| General obesity/overweight | 34/67 · 50.7% | 17/34 · 50.0% | 18/34 · 52.9% | 15/34 · 44.1% |
| Diabetes / prediabetes enriched | 14/67 · 20.9% | 10/14 · 71.4% | 12/14 · 85.7% | 11/14 · 78.6% |
| Cardiorenal / BP / OSA enriched | 7/67 · 10.4% | 1/7 · 14.3% | 2/7 · 28.6% | 3/7 · 42.9% renal |
| Other comorbidity/enriched | 5/67 · 7.5% | 2/5 · 40.0% | 2/5 · 40.0% | 2/5 · 40.0% glycaemic |
| Knee osteoarthritis enriched | 4/67 · 6.0% | 4/4 · 100.0% | 4/4 · 100.0% | 4/4 · 100.0% MSK |
| Genetic obesity / leptin deficiency | 2/67 · 3.0% | 1/2 · 50.0% | 2/2 · 100.0% | 2/2 · 100.0% BMI |
| MASH/NASH or liver enriched | 1/67 · 1.5% | 1/1 · 100.0% | 1/1 · 100.0% | 1/1 · 100.0% liver |
The obesity endpoint map splits into two commercially important designs: broad general-obesity trials, where weight is common but not universal, and diabetes/prediabetes-enriched trials, where weight and glycaemic endpoints travel together. Smaller enriched populations, especially knee osteoarthritis and genetic obesity, use more disease-specific endpoint anchors.
Peptide/protein/enzyme trials were the dominant modality group, appearing in 48/67 trials (71.6%). They were also the most weight-anchored: 33/48 peptide/protein/enzyme trials (68.8%) used body-weight change as a primary endpoint category, compared with 4/8 monoclonal-antibody trials (50.0%) and 2/8 small-molecule trials (25.0%).
| Modality mention | Trials | Primary body weight | Safety any role | BMI any role |
|---|---|---|---|---|
| Peptide/protein/enzyme | 48/67 · 71.6% | 33/48 · 68.8% | 25/48 · 52.1% | 19/48 · 39.6% |
| Small molecule | 8/67 · 11.9% | 2/8 · 25.0% | 1/8 · 12.5% | 1/8 · 12.5% |
| Monoclonal antibody | 8/67 · 11.9% | 4/8 · 50.0% | 2/8 · 25.0% | 2/8 · 25.0% |
| Other / diagnostic / unspecified | 11/67 · 16.4% | 2/11 · 18.2% | 1/11 · 9.1% | 0/11 · 0.0% |
The current European obesity Phase II–III endpoint standard is largely being set by peptide/protein/enzyme programs. Small-molecule and monoclonal-antibody programs are present but less frequent, so modality-specific comparisons should be read as directional rather than as a mature competitive benchmark.
All 67 included trials had an initial CTIS submission date and first authorization date in the endpoint context. The median initial-submission-to-first-authorization interval was 102 days overall; Phase II trials had a median of 68 days, while Phase III trials had a median of 106.5 days. Phase III authorizations increased from 10 trials in 2024 to 19 in 2025 and 29 in 2026.
| Authorization year | Phase II trials | Phase III trials | Median CTIS interval |
|---|---|---|---|
| 2024 | 6 | 10 | 65.5 days |
| 2025 | 2 | 19 | 105 days |
| 2026 | 1 | 29 | 108.5 days |
The European obesity pipeline in this dataset is increasingly Phase III-heavy, and CTIS timing lengthens as the cohort shifts toward larger confirmatory submissions. For planning EU obesity trial submissions, the observed benchmark is roughly 3–4 months to first authorization, with Phase III running longer than Phase II.
The same dataset also answers whether obesity trials are secondary-endpoint heavy and whether pediatric obesity trials use different endpoint anchors. Across the cohort, there were 689 recorded endpoint entries: 74 primary (10.7%), 614 secondary (89.1%), and 1 exploratory/other (0.1%). Pediatric trials accounted for 7/67 trials (10.4%); 6/7 pediatric trials (85.7%) measured BMI or BMI SDS, and 4/7 (57.1%) measured body-weight endpoints.
| Adjacent answerable question | Numeric answer |
|---|---|
| Are obesity endpoint packages mainly secondary-heavy? | 614/689 endpoint entries · 89.1% were secondary. |
| How often did trials include exploratory/other endpoints? | 1/67 trials · 1.5% had an exploratory/other endpoint. |
| Are pediatric trials endpoint-distinct? | 6/7 pediatric trials · 85.7% used BMI/BMI SDS; 4/7 · 57.1% used body-weight endpoints. |
| Are orphan-designated obesity trials present? | 1/67 trials · 1.5% had orphan-drug context. |
The adjacent signal is clear: EU obesity submissions are not exploratory-endpoint led; they are secondary-endpoint dense. Pediatric obesity trials are the main exception to the adult weight-change pattern because BMI and BMI SDS become the most consistent measurement language.