MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Petrelintide Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Petrelintide (ZP8396) is a long-acting amylin receptor agonist in development by Zealand Pharma and Roche for obesity. It is a 36-amino-acid acylated analog of human amylin that activates amylin and calcitonin receptors to boost satiety, slow gastric emptying, and cut food intake, a mechanism distinct from and potentially complementary to GLP-1 drugs such as semaglutide. With a terminal half-life near 10 days and roughly 85% subcutaneous bioavailability, it is dosed once weekly by subcutaneous injection (trials NCT05613387 and NCT06662539). In studies, maintenance doses of 2.4, 4.8, and 9.0 mg produced mean weight loss of about 4.8% to 8.6% over 16 weeks, and the Phase 2b ZUPREME-1 trial reported up to 10.7% at 42 weeks, with gastrointestinal tolerability comparing favorably to placebo. Petrelintide is investigational and not approved by any regulator; the figures here are an educational reference only.
Reconstitute: Add 1 mL bacteriostatic water → 10 mg/mL concentration.
Typical dose: 2.4–9.0 mg once weekly (trial maintenance)
Easy measuring: At 10 mg/mL, 1 unit = 0.01 mL = 0.1 mg (100 mcg) on a U-100 insulin syringe.
Storage: Lyophilized powder stored frozen at −20 °C; reconstituted solution refrigerated at 2–8 °C and used within about 4 weeks. Protect from light, do not freeze once in solution, and avoid shaking.
Half-life: Approximately 10 days (terminal); ~85% subcutaneous bioavailability, dose-proportional from 0.6–9.0 mg, supporting once-weekly dosing.
Route: Subcutaneous injection (abdomen, thigh, or upper arm), once weekly with stepwise dose escalation.
Status: Investigational amylin receptor agonist (Zealand Pharma/Roche); Phase 2 complete, not FDA- or EMA-approved.
About Petrelintide
Petrelintide (ZP8396) is an investigational long-acting amylin receptor agonist that, unlike GLP-1 drugs, drives weight loss primarily through amylin and calcitonin receptor signaling to amplify satiety and slow gastric emptying [1][8]. It is genuinely a subcutaneous, once-weekly injectable, so unlike the oral or topical compounds catalogued elsewhere on this site, the reconstitution figures below map directly onto the real-world clinical route.\n\nThis guide models a 10 mg vial reconstituted with 1.0 mL of bacteriostatic water (10 mg/mL) so doses land cleanly on a U-100 insulin syringe: 0.6 mg ≈ 6 units, 2.4 mg ≈ 24 units, 4.8 mg ≈ 48 units, and 9.0 mg ≈ 90 units. Clinical trials use a slow dose-escalation approach, starting well below the maintenance dose and stepping up every two to four weeks, to limit nausea and other gastrointestinal effects before reaching the 2.4, 4.8, or 9.0 mg maintenance levels [3][6].\n\nFrequency: Once weekly, on the same day each week, injected subcutaneously into the abdomen, thigh, or upper arm with site rotation. Petrelintide is not FDA- or EMA-approved and is presented here for educational purposes only, not as medical advice.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 1.0 mL of bacteriostatic water into a sterile syringe.
Inject the water slowly down the inner glass wall of the 10 mg Petrelintide vial; do not spray directly onto the lyophilized powder, and avoid shaking.
Swirl gently until the solution is completely clear; the result is a 10 mg/mL concentration, i.e. 100 mcg per U-100 insulin-syringe unit.
Swab the stopper, invert the vial, and draw the prescribed dose: 0.6 mg = 6 units, 2.4 mg = 24 units, 4.8 mg = 48 units, 9.0 mg = 90 units.
Inject subcutaneously into the abdomen, thigh, or upper arm once weekly, rotating sites; store the vial refrigerated at 2–8 °C and discard after about 4 weeks.
Interactive Petrelintide Syringe Calculator
Currently visualizing the 10 mg vial reconstituted with 1 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 10mg dry powder in 1mL water yields 10.00 mg/mL. To evaluate a 250mcg dose, pull to 2.5 units (3 syringe ticks).
U-100 Syringe Representation
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Phase | Dose per injection | Units (per injection) |
|---|---|---|
| Initiation / titration (weeks 1–4) | 600 mcg | 6 units (0.06 mL) |
| Low maintenance (2.4 mg cohort) | 2400 mcg (2.4 mg) | 24 units (0.24 mL) |
| Mid maintenance (4.8 mg cohort) | 4800 mcg (4.8 mg) | 48 units (0.48 mL) |
| High maintenance (9.0 mg cohort) | 9000 mcg (9 mg) | 90 units (0.90 mL) |
Administration guidelines: Refer to guidelines | 1 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 10 mg vial.
Peptide Vials (Petrelintide, 10 mg each):
- check8-week course: about 2 vials titrating to 2.4 mg/week, ~4 vials at 4.8 mg/week, or up to ~8 vials at 9.0 mg/week.
- check12-week course: roughly 3 vials (2.4 mg), 6 vials (4.8 mg), or 12 vials (9.0 mg).
- check16-week course: roughly 4 vials (2.4 mg), 8 vials (4.8 mg), or 16 vials (9.0 mg).
- checkHigher cohorts use far more peptide per week, since a 9.0 mg dose draws 90 of the 100 units in each reconstituted 10 mg vial.
Insulin Syringes (U-100):
- checkOne syringe per weekly injection plus spares: about 10 for an 8-week course.
- checkAbout 14 for a 12-week course (12 doses plus spares).
- checkAbout 18 for a 16-week course (16 doses plus spares).
- checkUse 0.5 mL or 1 mL U-100 syringes; a 9.0 mg dose (90 units) requires a 1 mL syringe.
Bacteriostatic Water (30 mL bottles):
- checkUse 1 mL per 10 mg vial for reconstitution.
- checkOne 30 mL bottle covers a full 8-week course even at the highest 9.0 mg cohort (up to ~8 vials = 8 mL).
- checkOne 30 mL bottle also covers most 12- to 16-week low- and mid-dose courses; high-dose 16-week courses (up to 16 vials) need ~16 mL.
- checkKeep an extra bottle on hand for the 9.0 mg cohort over longer courses.
Alcohol Swabs:
- checkUse two per injection (one for the vial stopper, one for the skin).
- checkAbout 20–25 swabs for an 8-week course.
- checkAbout 28–32 swabs for a 12-week course.
- checkAbout 36–40 swabs for a 16-week course; keep extras for site preparation.
Mechanism of Action (MOA)
Petrelintide (ZP8396) is a 36-amino-acid acylated peptide derived from the sequence of human amylin, the pancreatic beta-cell hormone co-secreted with insulin after meals. A lipid (acyl) side chain promotes reversible binding to serum albumin, slowing renal clearance and extending the molecule's residence in the circulation, the same protraction strategy used in long-acting GLP-1 analogs. Petrelintide is engineered to act as a balanced agonist of both the amylin receptors and the calcitonin receptor, the receptor family through which native amylin signals [1][8].\n\nPhysiologically, amylin is a satiety hormone. It acts on the area postrema and nucleus tractus solitarius in the hindbrain and on hypothalamic circuits to enhance meal-ending satiation, reduce food intake, slow gastric emptying, and suppress postprandial glucagon. Because this pathway is mechanistically distinct from incretin (GLP-1) signaling, amylin agonism is being pursued both as monotherapy and as a complement to GLP-1 drugs; preclinically the two classes act additively on appetite [8]. In diet-induced obese rodents, petrelintide selectively reduced intake of a high-fat diet and lowered fat mass while largely preserving lean (muscle) mass, a profile that has driven interest in amylin agonists as quality-weight-loss agents [8].\n\nPharmacokinetics support once-weekly dosing. After subcutaneous injection petrelintide shows roughly 85% bioavailability and dose-proportional exposure (Cmax and AUC) across the 0.6 mg to 9.0 mg range, with a terminal half-life of approximately 10 days [7][8]. Steady state is reached after several weekly doses, which is why trials use a stepwise escalation, starting well below the maintenance dose and increasing every two to four weeks, to let gastrointestinal tolerance develop before reaching 2.4, 4.8, or 9.0 mg [3][4][6].\n\nDownstream, sustained amylin-receptor activation translates reduced energy intake into clinically meaningful weight loss: about 4.8%, 8.6%, and 8.3% mean reductions at 2.4, 4.8, and 9.0 mg over 16 once-weekly doses in the multiple-ascending-dose study [6][7], and up to 10.7% at week 42 in the larger Phase 2b ZUPREME-1 trial [2][3]. Reported gastrointestinal effects (mainly nausea) were generally mild and, in the most effective ZUPREME-1 arm, vomiting occurred less often than with placebo [2][6].\n\nUnlike many compounds catalogued on this site, petrelintide's real-world route genuinely is subcutaneous injection, so the reconstitution figures here correspond to the clinical route rather than serving only as a measurement convention. Even so, petrelintide remains investigational: it is not approved by the FDA, EMA, or any other regulator, and the protocol on this page is an educational reference only, not a prescription or medical advice [1][2].
Clinical Trial Efficacy Highlights
- starThe first-in-human single-ascending-dose trial (ADA 2023 abstract 92-LB) randomized 56 healthy lean and overweight subjects to petrelintide or placebo across seven cohorts spanning 0.04 mg to 2.4 mg; single doses were well tolerated and produced dose-dependent reductions in body weight, supporting development of ZP8396 as an obesity treatment [5].
- starIn the 16-week multiple-ascending-dose study (Part 2; ADA 2024 abstract 1668-P and Zealand topline data), once-weekly petrelintide titrated to 2.4, 4.8, and 9.0 mg produced mean body-weight reductions of roughly 4.8%, 8.6%, and 8.3% respectively, versus about 1.7% for pooled placebo, with dose escalation every second week [6][7].
- starThe Phase 2b ZUPREME-1 dose-finding trial (NCT06662539) enrolled 493 adults with overweight or obesity (mean BMI ~37 kg/m²) across five once-weekly dose arms escalated every fourth week, and reported up to 10.7% mean body-weight reduction at week 42 versus 1.7% with placebo (p<0.001) [2][3].
- starTolerability in ZUPREME-1 was a headline finding: discontinuation due to adverse events was 4.8% with petrelintide versus 4.9% with placebo, there was no vomiting in the maximally effective treatment arm, and diarrhea and constipation remained in the single-digit range, with nausea less common than in the earlier Phase 1b study [2].
- starPharmacokinetic characterization showed dose-proportional exposure from 0.6 mg to 9.0 mg, roughly 85% subcutaneous bioavailability, and a terminal half-life of about 10 days, confirming a profile suitable for once-weekly administration [7][8].
- starPreclinical studies in diet-induced obese rats demonstrated that petrelintide selectively reduced high-fat-diet intake and lowered fat mass while preserving lean mass, the rationale for positioning amylin agonists as agents that may protect muscle during weight loss [8].
- starThe mechanistic complementarity between amylin and GLP-1 agonism underpins combination strategies; reviews of amylin receptor activators highlight petrelintide alongside cagrilintide as candidates for both monotherapy and co-administration with incretin drugs, and Roche's 2025 collaboration with Zealand explicitly targets combination regimens [1][8].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningGastrointestinal effects are the most common adverse events, with nausea predominating; these are typically mild to moderate, dose- and titration-dependent, and tend to ease after the first weeks at a given dose [2][6].
- warningVomiting, diarrhea, and constipation were reported but at low rates; in the most effective ZUPREME-1 arm vomiting occurred less frequently than with placebo, and diarrhea and constipation stayed in the single-digit percentage range [2].
- warningInjection-site reactions (redness, itching, transient nodules) can occur with any subcutaneous peptide; rotate injection sites between the abdomen, thigh, and upper arm.
- warningPronounced early satiety and appetite suppression can reduce food and fluid intake; monitor hydration and adequate protein and micronutrient intake, particularly during dose escalation.
- warningAmylin agonism suppresses glucagon and can affect glucose handling; the theoretical risk of hypoglycemia is greatest if combined with insulin or insulin secretagogues, which warrants medical supervision in people with diabetes.
- warningRapid or large weight loss carries general risks (gallbladder events, loss of lean mass); although preclinical data suggest petrelintide preserves lean mass, long-term human body-composition and cardiovascular safety data are not yet available.
- warningSafety in pregnancy, breastfeeding, children, and people with significant renal, hepatic, or cardiac disease has not been established; petrelintide should not be assumed safe in these groups.
- warningRegulatory and research status: petrelintide is investigational and is NOT approved by the FDA, EMA, or any other regulator. It is available only within clinical trials, and the dosing and reconstitution figures here are for education only, not medical advice.
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Petrelintide dosage?expand_more
In clinical trials Petrelintide is given as a once-weekly subcutaneous injection, titrated slowly to maintenance doses of 2.4 mg, 4.8 mg, or 9.0 mg. Escalation steps (for example starting near 0.6 mg and increasing every two to four weeks) are used to reduce nausea. There is no approved Petrelintide dosage because the drug is investigational; the figures here are an educational reference only, not a prescription.
Is Petrelintide FDA approved?expand_more
No. Petrelintide (ZP8396) is investigational and is not approved by the FDA, the EMA, or any other regulator. It has completed Phase 2 development (the ZUPREME-1 dose-finding trial) under Zealand Pharma and a 2025 Roche collaboration, with Phase 3 anticipated. It is available only within clinical trials, and any non-trial use is unapproved and for research or educational purposes only.
What is the half-life of Petrelintide?expand_more
Petrelintide has a terminal half-life of approximately 10 days. An acyl side chain that binds serum albumin slows clearance, and subcutaneous bioavailability is roughly 85% with dose-proportional exposure from about 0.6 mg to 9.0 mg. This long half-life is what makes convenient once-weekly dosing possible.
How is Petrelintide reconstituted and administered?expand_more
In this educational model a 10 mg vial is reconstituted with 1.0 mL of bacteriostatic water to give 10 mg/mL (100 mcg per insulin-syringe unit). On a U-100 syringe, 0.6 mg is 6 units, 2.4 mg is 24 units, 4.8 mg is 48 units, and 9.0 mg is 90 units. Petrelintide is genuinely a subcutaneous injectable, given once weekly into the abdomen, thigh, or upper arm with site rotation.
Can Petrelintide be stacked with semaglutide or tirzepatide?expand_more
Amylin agonism works through a pathway distinct from GLP-1 receptor agonists like semaglutide and tirzepatide, and preclinical data suggest the two classes act additively on appetite, which is why combinations are an active research focus (mirroring the cagrilintide-plus-semaglutide approach). However, no such combination involving Petrelintide is approved, dosing for combinations is not established, and stacking should not be attempted outside a supervised clinical trial.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Petrelintide, plus the universal dosing calculator.
Academic References & Study Citations
Petrelintide. Wikipedia. Overview of ZP8396, a long-acting amylin analog developed by Zealand Pharma; 2025 Roche collaboration and investigational status. View Scientific Paper →
Roche. Roche announces positive Phase II results for petrelintide, an amylin analog developed for people living with overweight and obesity. Media release, 5 March 2026 (ZUPREME-1; up to 10.7% mean weight loss at 42 weeks). View Scientific Paper →
ClinicalTrials.gov. A Randomized, Double-blind, Phase 2, Dose-finding Trial of Once Weekly Petrelintide Compared With Placebo in Participants With Obesity or Overweight With Weight Related Comorbidities (ZUPREME-1). NCT06662539. View Scientific Paper →
ClinicalTrials.gov. A Research Study Looking at the Safety of Multiple Doses of ZP8396 and How It Works in the Body of Healthy Participants. NCT05613387. View Scientific Paper →
92-LB: Safety, Tolerability, and Clinical Effects of ZP8396, a Novel Long-Acting Amylin Analog—A Single Ascending Dose Trial. Diabetes. 2023;72(Supplement_1):92-LB. American Diabetes Association Scientific Sessions abstract. View Scientific Paper →
1668-P: Novel Once-Weekly Amylin Analog Petrelintide (ZP8396) Is Well Tolerated with Improved GI Tolerability after Multiple Dosing. Diabetes. 2024;73(Supplement_1):1668-P. American Diabetes Association Scientific Sessions abstract. View Scientific Paper →
Zealand Pharma. Safety, Tolerability, and Clinical Effects of Petrelintide — presentation at ObesityWeek 2024, including 16-week multiple-ascending-dose efficacy and pharmacokinetic data. View Scientific Paper →
A Review of Amylin Peptide Receptor Activators for Obesity Pharmacotherapy. Bentham Science. Review covering amylin analogs including petrelintide and cagrilintide, mechanism, and combination potential. View Scientific Paper →