BI 456906 (Survodutide) in Clinical Trials: What Researchers Are Studying

1) What is BI 456906 (Survodutide)?

BI 456906 is an investigational medicine being tested in clinical trials. In many trials it is also called survodutide. The studies provided describe BI 456906 as a solution for injection that is usually given as a subcutaneous injection (an injection under the skin).

Across trials, researchers are exploring BI 456906 for weight-related conditions and metabolic health, including overweight/obesity, type 2 diabetes, kidney disease outcomes, and liver disease outcomes. Some trials are also focused on very basic questions, such as how much of the drug gets into the blood and how the body removes it.

2) How BI 456906 is given in studies

Most clinical trials listed use injections under the skin. Common patterns include:

• Once-weekly dosing: Many studies give BI 456906 once a week, especially weight loss and safety studies.
• Titration (dose escalation): Several studies increase the dose slowly over time. This is often done to improve tolerability, meaning to help participants stay on treatment without side effects forcing them to stop or reduce the dose.
• Single-dose studies: Some early Phase I trials give only one dose, mainly to measure drug levels in blood and short-term safety.

3) What conditions are being studied

Based on the included trial records, BI 456906 is being studied in:

• Obesity and overweight (including people without diabetes and specific regional studies such as in Chinese participants)
• Type 2 diabetes mellitus (including people on metformin with high blood sugar)
• Chronic kidney disease (with albuminuria) and separate studies in renal impairment to understand drug levels
• Liver diseases, including cirrhosis with varying severity and a Phase III trial in presumed/confirmed NASH

4) Weight loss trials in overweight or obesity

Several trials are designed to test whether BI 456906 helps people lose weight and improve body measurements such as waist size.

Examples of what these weight-focused trials measure include:

• Percentage change in body weight from baseline to a specific time point (for example Week 46, Week 52, or Week 76, depending on the trial).
• Whether participants reach weight loss milestones such as losing at least 5%, 10%, 15%, or 20% of their starting weight.
• Waist circumference changes (an abdominal measurement often used as a marker of central body fat).
• Blood pressure changes (systolic and diastolic).

One Phase II dose-finding study in obesity/overweight (without diabetes) compares multiple BI 456906 doses with placebo over 46 weeks, focusing on percent body weight change and weight-loss thresholds (≥5%, ≥10%, ≥15%).

A Phase III study in Chinese participants with overweight/obesity compares two doses (3.6 mg and 4.8 mg) against placebo and measures weight change and multiple cardiometabolic measures at Week 52.

There are also Phase III European registry trials described for people with overweight/obesity without type 2 diabetes, where the main endpoints include percent weight change and achieving ≥5% weight loss by Week 76, with additional weight-loss thresholds and waist circumference and blood pressure among secondary endpoints.

5) Trials in type 2 diabetes

BI 456906 is also studied in adults with type 2 diabetes mellitus. In one Phase II dose-finding trial, participants who take metformin but still have high blood sugar receive BI 456906 (different dose groups) or placebo, and there is also an open-label semaglutide group.

Key measurements in the type 2 diabetes study include:

• HbA1c change (HbA1c is a blood test showing average blood sugar over the past 2–3 months)
• Change in body weight and waist circumference
• Percentage of participants reaching ≥5% or ≥10% weight loss over 16 weeks

In addition, a Phase III European registry trial is described for people with overweight/obesity and type 2 diabetes. Its primary endpoints include percent body weight change and achieving ≥5% weight loss by Week 76, with HbA1c included among secondary endpoints.

6) Kidney-focused trials (CKD and renal impairment)

Kidney-related research with BI 456906 appears in two different ways: (1) outcome trials in people who already have kidney disease, and (2) drug-level studies in people with reduced kidney function.

CKD outcome trial (albuminuria reduction)

The ARTIST-CKD trial studies weekly subcutaneous BI 456906 (survodutide) in people with chronic kidney disease and elevated albuminuria. The primary outcome is change in first morning void UACR (urine albumin-to-creatinine ratio), averaged at weeks 32 and 36 to reduce day-to-day variability. Secondary outcomes include eGFR and measured GFR using iohexol in a subset.

Renal impairment PK study

Another study gives a single BI 456906 dose to participants with normal kidney function and to participants with mild, moderate, or severe renal impairment. The goal is to compare BI 456906 blood levels using measures like AUC and Cmax, and to record drug-related adverse events.

7) Liver-focused trials (cirrhosis/hepatic impairment and NASH)

Trials address liver health in two main ways:

• How liver impairment changes BI 456906 levels and tolerability
• Whether BI 456906 reduces liver fat and weight in people with NASH

Hepatic impairment and cirrhosis study

A two-part study compares drug levels after a single dose in healthy people versus people with cirrhosis grouped by Child-Turcotte-Pugh (CTP) class (A, B, C). It also studies longer exposure in people with overweight/obesity with or without cirrhosis, using multiple weekly doses over 28 weeks with a titration plan, and measures treatment-emergent adverse events.

NASH Phase III trial

A Phase III trial is described for participants with overweight/obesity and presumed or confirmed non-alcoholic steatohepatitis (NASH). It evaluates BI 456906 once weekly as an add-on to reduced-calorie diet and increased physical activity versus placebo. The two primary goals are:

• Achieving at least a 30% relative reduction in liver fat measured by MRI-PDFF at Week 48
• Improving relative change in body weight from baseline to Week 48

8) Heart and cardiovascular safety studies

Because new medicines can sometimes affect the heart, several BI 456906 trials focus on cardiovascular safety.

Heart rhythm (QTcI) safety study

One trial evaluates cardiac safety parameters in adults with overweight/obesity using ECG testing. A key outcome is the time-matched change from baseline in QTcI during BI 456906 dosing. The trial uses moxifloxacin as a “positive control,” which means it is known to change heart rhythm in a detectable way and helps confirm that the ECG analysis can pick up changes.

Phase 3 cardiovascular outcomes safety study (EU registry)

A Phase 3, randomized, double-blind, event-driven study is described in people with overweight/obesity and established cardiovascular disease or chronic kidney disease and/or at least two weight-related cardiovascular risk factors. The primary endpoint is time to first occurrence of a composite of serious cardiovascular outcomes (including cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, ischemia-related coronary revascularization, or heart failure events).

9) Brain and receptor imaging studies

Some studies use imaging to understand how BI 456906 may affect biological pathways linked to appetite and metabolism.

Brain activity study using fMRI

One Phase I study in people with overweight/obesity tests single doses of BI 456906 alone, another drug (BI 1820237) alone, and the combination, compared with placebo. The main outcome is change in brain activity measured as BOLD signal on functional MRI (fMRI) in response to food-related visual stimuli and nutrient-specific food preference tasks.

Receptor occupancy study using PET/MRI

Another Phase I study compares BI 456906 with semaglutide in people with obesity and uses injected tracers with imaging to measure:

• Glucagon receptor occupancy in the liver (PET)
• GLP-1 receptor occupancy in the pancreas (PET)

10) Studies on drug levels: PK, metabolism, and formulations

Many early-stage studies focus on how BI 456906 is absorbed and processed, often using blood sampling over time to calculate PK measurements like AUC and Cmax.

Single rising dose safety/PK study in healthy volunteers

A Phase I trial evaluates safety and tolerability after single rising subcutaneous doses in healthy male subjects, and explores pharmacokinetics and pharmacodynamics after single dosing.

Multiple dose titration scheme trials

Several studies in obesity/overweight (including a study in healthy Japanese men with BMI 23–40 kg/m²) focus on different dose escalation schedules and look at how many participants withdraw from up-titration, along with PK measures after dosing.

Metabolism and excretion (mass balance) study

A Phase I study uses BI 456906 (C-14), a radiolabeled version of the drug, to track drug-related material and understand mass balance, excretion pathways (urine and feces), and metabolism after a single dose.

Formulation (bioavailability) comparison studies

Two studies compare different BI 456906 formulations in healthy participants to evaluate relative bioavailability using AUC and Cmax. One compares formulation A versus B2 in a two-period crossover design, and another compares formulation A with formulations B and C in a three-period crossover design.

11) Drug interaction study with an oral contraceptive

One Phase I study in otherwise healthy women with overweight/obesity examines whether multiple doses of BI 456906 change blood levels of the contraceptive Microgynon®, which contains ethinylestradiol and levonorgestrel. The main outcomes are AUC and Cmax for each hormone when taken alone versus during BI 456906 dosing.

12) Understanding common trial measurements

Clinical trials use specific measurements to answer specific questions. Here are common ones seen in these BI 456906 trials:

• HbA1c: A long-term blood sugar marker (average over ~2–3 months). Trials in type 2 diabetes use it to assess blood sugar control.
• AUC and Cmax: Blood level measurements used in pharmacokinetics. AUC reflects overall exposure; Cmax reflects the peak concentration.
• QTcI: An ECG-based heart rhythm measurement corrected for heart rate on an individual basis. Changes are monitored to evaluate cardiac safety.
• UACR: A urine test for albumin leakage from the kidneys. Lower UACR can indicate improved kidney-related outcomes in albuminuria studies.
• MRI-PDFF: An imaging method that estimates liver fat percentage. NASH trials use it to evaluate liver fat reduction.