Survodutide: Dosing Protocols

Investigational Status#

Survodutide (BI 456906) is an investigational compound currently in Phase 3 clinical trials. It is not approved by the FDA, EMA, or any other regulatory authority. All dosing information presented here is derived from published Phase 2 clinical trial data and publicly available trial design information. There is no approved prescribing information for survodutide. The dosing protocols described below reflect clinical trial designs and should not be interpreted as prescribing guidance.

Dose Escalation in the COURAGE Trial (Obesity)#

The COURAGE trial was the pivotal Phase 2 dose-finding study for survodutide in adults with overweight or obesity (BMI 28 or greater) without diabetes. The trial enrolled 387 participants randomized to one of four survodutide dose groups or placebo for 46 weeks.

Dose Groups and Escalation#

The trial evaluated four survodutide maintenance doses: 0.6 mg, 2.4 mg, 3.6 mg, and 4.8 mg administered once weekly by subcutaneous injection. All groups except the 0.6 mg arm underwent stepwise dose escalation from a lower starting dose to the target maintenance dose over several weeks. This escalation approach was designed to allow gastrointestinal adaptation and minimize the incidence and severity of nausea, vomiting, and diarrhea.

The dose escalation schedule involved increasing the dose at defined intervals, with each intermediate step maintained for a period sufficient to allow GI adaptation before the next increase. The specific intermediate dose steps and timing intervals were defined in the trial protocol.

Dose-Response Relationship#

The COURAGE trial demonstrated a clear dose-dependent relationship for weight loss. The treatment difference versus placebo was approximately:

• 2.4 mg: approximately 8.1 percentage points
• 3.6 mg: approximately 10.4 percentage points
• 4.8 mg: approximately 12.1 percentage points

At the 4.8 mg dose, 83% of participants achieved at least 5% body weight loss, and 57% achieved at least 15% weight loss at 46 weeks. These results informed the dose selection for the Phase 3 ACHIEVE program.

Cardiometabolic Improvements#

Across dose groups, survodutide treatment was associated with improvements in multiple cardiometabolic parameters beyond weight loss, including reductions in waist circumference, improvements in lipid profiles (triglycerides, non-HDL cholesterol), reductions in high-sensitivity C-reactive protein, and stable or improved glycemic parameters. These improvements were generally dose-dependent.

Dose Escalation in the MASH Trial#

The Phase 2b trial for survodutide in MASH enrolled 293 patients with biopsy-confirmed MASH and liver fibrosis stages F1-F3. The trial evaluated three survodutide dose groups (2.4 mg, 4.8 mg, and 6.0 mg weekly) and placebo for 48 weeks.

MASH Trial Dose Design#

The MASH trial introduced the 6.0 mg weekly dose, which was not evaluated in the COURAGE obesity trial. This higher dose was included to explore whether additional glucagon and GLP-1 receptor activation would produce greater improvements in liver histology. All dose groups underwent stepwise escalation from lower starting doses.

The 4.8 mg dose group results demonstrated statistically significant and clinically meaningful improvements in MASH resolution without worsening of fibrosis, fibrosis improvement by at least one stage, and liver fat content reduction.

Phase 3 ACHIEVE Program Dosing#

Based on the Phase 2 results, Boehringer Ingelheim initiated the Phase 3 ACHIEVE clinical program. The Phase 3 trials are evaluating survodutide at doses up to 6.0 mg weekly with optimized dose escalation schedules.

Optimized Escalation#

A key design change in the Phase 3 program is the implementation of more gradual dose escalation compared to Phase 2. This modification was informed by the observation that the majority of gastrointestinal adverse events occurred during dose escalation periods, and that treatment discontinuation due to GI intolerance was a significant factor in the higher-dose groups. The more gradual escalation is expected to improve patient retention and overall tolerability while still achieving target maintenance doses.

Trial Population#

The ACHIEVE program includes trials in both obesity (ACHIEVE-1, evaluating weight loss in adults without diabetes) and MASH (multiple trials evaluating histological endpoints). The parallel pursuit of both indications reflects the differentiated mechanism of survodutide, where the glucagon receptor component may provide particular advantages for hepatic fat reduction in MASH.

Administration Details#

Route of Administration#

Survodutide is administered by subcutaneous injection once weekly. In clinical trials, the injection has been performed by study participants after appropriate training, consistent with the self-administration model established by other injectable peptide therapies in the metabolic class.

Injection Sites#

Based on standard practice for subcutaneous peptide injections and the approach used for related metabolic therapies, injection sites include the abdomen, anterior thigh, and upper arm. Rotation of injection sites between doses is recommended to minimize injection site reactions and localized tissue effects.

Timing and Frequency#

Survodutide is administered once weekly, on the same day each week. In clinical trials, the injection could be given at any time of day. The approximately 6-7 day estimated half-life supports the weekly dosing interval by maintaining therapeutic plasma concentrations throughout the dosing period.

Storage and Handling#

Specific storage requirements for survodutide have not been publicly detailed beyond what is standard for the pharmacological class. As a lipid-modified peptide therapeutic, survodutide is expected to require refrigerated storage at 2-8 degrees C (36-46 degrees F) with protection from light. A defined period of room temperature stability for patient convenience is expected but has not been publicly specified.

Clinical trial protocols define the specific storage and handling requirements for the investigational product. These conditions will be finalized and disclosed in the product labeling if survodutide receives regulatory approval.

Formulation#

The final commercial formulation of survodutide has not been established. In clinical trials, survodutide has been provided as an injectable solution in a delivery device suitable for subcutaneous self-administration. The concentration, excipients, and device specifications are defined by the clinical trial protocol and are expected to be refined during the registration process.

Comparison with Approved Agent Dosing#

For context, the following table compares the investigational dosing of survodutide with the approved dosing schedules of related therapies:

Missed Dose and Discontinuation Considerations#

Specific guidance on missed doses and treatment discontinuation for survodutide has not been publicly established. Based on the pharmacokinetic profile and dosing approaches used for related therapies, a missed dose would likely be administered as soon as possible within a defined window after the scheduled date, with the next dose administered on the regular schedule. These details will be specified in the prescribing information if survodutide receives regulatory approval.

Preliminary data from the COURAGE trial treatment-free follow-up period showed partial weight regain after discontinuation, consistent with findings from other incretin-based therapies. This observation suggests that chronic treatment may be necessary to maintain therapeutic benefits, though specific protocols for dose reduction or treatment cessation have not been established.

Related Reading#

• Survodutide overview and research guide
• Survodutide side effects profile
• Survodutide research evidence