Clinical Trial Intelligence

Which Endpoints Are Measured Most Often in European Endocrinology Phase 2 & 3 Trials?

5 July 2026

Across 231 unique CTIS-authorized European endocrinology Phase 2 & 3 trials, safety/tolerability was the most common endpoint family, appearing in 116 trials (50.2%). Glycaemic control appeared in 89 trials (38.5%), patient-reported quality-of-life or symptom measures in 88 (38.1%), and body-weight/BMI/anthropometry endpoints in 80 (34.6%). Obesity/overweight was the largest disease group with 59 trials, where body-weight endpoints dominated primary measurement in 36 trials (61.0%).

231
unique CTIS endocrinology Phase 2 & 3 trials
50.2%
measured safety or tolerability endpoints
59
obesity/overweight trials; largest disease group
96 days
median initial CTIS submission to first authorization

Safety is the broadest recurring endpoint family, but endocrine efficacy measurement is split across weight, glycaemia, QoL, and disease-specific composites

Safety/tolerability appeared in 116 of 231 trials (50.2%). Disease-specific or composite endpoints appeared in 103 trials (44.6%), glycaemic control in 89 (38.5%), patient-reported quality-of-life or symptoms in 88 (38.1%), and body-weight/BMI/anthropometry in 80 (34.6%).

Trials measuring each endpoint family, % of 231 unique trials
Safety / tolerability116 / 231 · 50.2%
Disease-specific / composite endpoints103 / 231 · 44.6%
Glycaemic control / insulin biology89 / 231 · 38.5%
Patient-reported QoL / symptoms88 / 231 · 38.1%
Body weight / BMI / anthropometry80 / 231 · 34.6%
Blood pressure / cardiovascular risk68 / 231 · 29.4%
PK / PD / exposure / immunogenicity57 / 231 · 24.7%
Lipids / inflammation / metabolic labs54 / 231 · 23.4%
Endpoint families counted once per trial when present in primary, secondary, or other endpoint fields.
Interpretation

Endocrinology trials are not anchored to one universal efficacy endpoint. Unlike oncology-style response endpoints, the CTIS endocrine dataset splits measurement across safety, metabolic biomarkers, body composition, patient-reported outcomes, and disease-specific responder definitions.

Primary endpoints are narrower; secondary endpoints carry most metabolic and QoL breadth

Among 202 trials with primary endpoint entries, disease-specific/composite endpoints led at 50 trials (24.8%), followed by body-weight/BMI/anthropometry in 48 (23.8%) and safety/tolerability in 40 (19.8%). Among 175 trials with secondary endpoints, safety appeared in 84 (48.0%), patient-reported QoL/symptoms in 82 (46.9%), and glycaemic control in 81 (46.3%).

Top endpoint families by role
Role Most frequent endpoint families
Primary
n=202		 Disease-specific/composite 50 (24.8%); body-weight/BMI/anthropometry 48 (23.8%); safety 40 (19.8%); glycaemic control 35 (17.3%); imaging/diagnostic 24 (11.9%).
Secondary
n=175		 Disease-specific/composite 87 (49.7%); safety 84 (48.0%); patient-reported QoL/symptoms 82 (46.9%); glycaemic control 81 (46.3%); body-weight/BMI/anthropometry 69 (39.4%).
Exploratory / other
n=6		 Safety, glycaemic control, lipids/metabolic labs, and disease-specific/composite endpoints each appeared in 2 trials (33.3% of trials with other endpoints).
Percentages use the number of trials with at least one endpoint in that role as denominator.
Interpretation

Primary endpoints are more likely to be a single anchor such as body weight, HbA1c, safety, or a disease-specific responder definition. Secondary endpoints are where CTIS endocrine protocols add broader metabolic panels, QoL tools, blood pressure, lipid, and PK/PD characterization.

Obesity trials drive body-weight endpoints, while diabetes and rare metabolic trials drive HbA1c, glucose, safety, and PK

Obesity/overweight was the largest disease group with 59 of 231 trials (25.5%). Type 2 diabetes/complications accounted for 27 trials (11.7%), Type 1 diabetes for 23 (10.0%), rare metabolic/genetic endocrine diseases for 29 (12.6%), adrenal/cortisol disorders for 13 (5.6%), and MASH/NASH/steatotic liver disease for 11 (4.8%).

Disease groups with sufficient sample size
Obesity / overweight59 trials

Body weight 41 (69.5%); waist circumference 27 (45.8%); QoL/PRO 27 (45.8%); blood pressure 26 (44.1%). Primary body-weight endpoint: 36 (61.0%).

Rare metabolic / genetic endocrine29 trials

Safety 20 (69.0%); QoL/PRO 11 (37.9%); PK exposure 8 (27.6%); immunogenicity/ADA 5 (17.2%). Largest sub-clusters included PKU 5, Fabry disease 2, and propionic acidemia 2.

Type 2 diabetes / complications27 trials

HbA1c 14 (51.9%); safety 11 (40.7%); body weight 10 (37.0%); glucose/FPG/CGM 10 (37.0%); blood pressure 9 (33.3%).

Type 1 diabetes23 trials

Safety 14 (60.9%); HbA1c 13 (56.5%); glucose/FPG/CGM 11 (47.8%); hypoglycaemia events 8 (34.8%); PK exposure 7 (30.4%).

MASH / NASH / steatotic liver disease11 trials

Liver fibrosis/histology 8 (72.7%); MRI-PDFF/liver fat 3 (27.3%); safety 3 (27.3%). Primary liver fibrosis or histology endpoint: 7 (63.6%).

Adrenal / cortisol disorders13 trials

Safety 8 (61.5%); hormonal biomarkers 5 (38.5%); PK exposure 4 (30.8%); body weight and QoL/PRO each 3 (23.1%).

Disease groups shown where n ≥ 10 trials or where clinically central to endocrine endpoint strategy.
Interpretation

Endpoint strategy is disease-led. Obesity trials are clearly weight-centric; diabetes trials remain anchored in HbA1c, glucose, and hypoglycaemia; MASH/NASH trials rely on fibrosis and liver-fat assessment; rare metabolic programs emphasize safety, PK, immunogenicity, and functional/QoL outcomes.

Phase 2 uses more safety and PK anchoring, while Phase 3 shifts toward body-weight, QoL, lipid, and cardiometabolic endpoints

The phase-specific CTIS view included 86 Phase 2-containing and 150 Phase 3-containing assignments. Phase 2 primary endpoints were led by safety in 27 of 82 primary-bearing trials (32.9%); Phase 3 primary endpoints were led by body weight in 35 of 125 primary-bearing trials (28.0%).

Phase 2 versus Phase 3 endpoint contrasts
Phase 2-containing

86 phase assignments

Primary: safety 27/82 (32.9%); body weight, PK, and UACR/eGFR each 8/82 (9.8%).
Secondary: safety 37/74 (50.0%); glucose/FPG/CGM 27/74 (36.5%); body weight 24/74 (32.4%); PK 22/74 (29.7%).
Phase 3-containing

150 phase assignments

Primary: body weight 35/125 (28.0%); safety 17/125 (13.6%); HbA1c 9/125 (7.2%).
Secondary: QoL/PRO 52/105 (49.5%); safety 44/105 (41.9%); lipids 41/105 (39.0%); body weight 37/105 (35.2%); HbA1c 35/105 (33.3%).
Role percentages use trials with that endpoint role inside each phase assignment.
Interpretation

Phase 2 endocrine protocols are more likely to use safety, PK, and biomarker signals to establish dose and biological plausibility. Phase 3 protocols broaden into patient-relevant and cardiometabolic secondary endpoints, especially QoL, lipids, blood pressure, HbA1c, and body weight.

Modality changes the endpoint center of gravity: peptides are weight/metabolic-heavy, advanced therapies are safety-heavy

Peptide/protein/enzyme trials and small-molecule trials were the two largest modality groups, with 89 and 85 trials respectively. Advanced therapy/RNA/cell-gene trials formed a smaller but analyzable group of 20 trials, where safety appeared in 16 (80.0%) and primary safety endpoints in 15 (75.0%).

Modality groups with sufficient trial counts
Modality group Most frequent measured endpoints
Peptide / protein / enzyme
n=89		 Body weight 48 (53.9%); safety 42 (47.2%); HbA1c 34 (38.2%); glucose/FPG/CGM 33 (37.1%); QoL/PRO 32 (36.0%).
Small molecule
n=85		 Safety 37 (43.5%); QoL/PRO 26 (30.6%); glucose/FPG/CGM 17 (20.0%); body weight 17 (20.0%); HbA1c 16 (18.8%).
Advanced therapy / RNA / cell-gene
n=20		 Safety 16 (80.0%); lipids 6 (30.0%); glucose/FPG/CGM 6 (30.0%); HbA1c 5 (25.0%); PK exposure 5 (25.0%).
Groups below n=20 were not used for comparative modality conclusions.
Interpretation

Peptide/protein/enzyme trials are strongly shaped by incretin-like obesity and diabetes programs, producing high body-weight and HbA1c use. Advanced therapy and RNA/cell-gene trials are less endpoint-standardized and more safety-led, consistent with earlier biological-risk characterization.

CTIS submission timing suggests endpoint packages need to be stable roughly three months before first authorization

Across all 231 trials, the median interval from initial CTIS submission to first authorization was 96 days, with an interquartile range of 40 to 115 days. Phase 2-containing assignments had a median interval of 87.5 days, while Phase 3-containing assignments had a median of 98 days.

Additional numeric insights from the same CTIS endpoint dataset
7.6
average secondary endpoints per Phase 3-containing assignment, versus 6.1 in Phase 2
58
paediatric trials; safety appeared in 35 (60.3%) and PK in 21 (36.2%)
43
orphan-designated trials; safety appeared in 29 (67.4%)
35.6%
of obesity/overweight trials had 10 or more secondary endpoints: 21 of 59
CTIS timing uses initial submission date and first authorization date available in the trial records.
Interpretation

For European CTIS submissions, endpoint strategy is not just a statistical-design question. Phase 3 endocrine submissions need wider secondary endpoint governance, while paediatric, orphan, and advanced-therapy programs need stronger safety, PK, and immunogenicity endpoint readiness before EU submission.

Definitions

CTIS means Clinical Trials Information System. HbA1c means glycated haemoglobin. FPG means fasting plasma glucose. CGM means continuous glucose monitoring. PK/PD means pharmacokinetic/pharmacodynamic. QoL/PRO means quality-of-life or patient-reported outcome. MRI-PDFF means magnetic resonance imaging proton-density fat fraction. UACR means urine albumin-creatinine ratio. ADA means anti-drug antibodies.