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.
Cotadutide Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Cotadutide (MEDI0382) is an investigational, lipidated 30-amino-acid peptide that acts as a balanced dual agonist of the GLP-1 and glucagon receptors, derived from the gut hormone oxyntomodulin by MedImmune/AstraZeneca. The GLP-1 arm lowers glucose and appetite while slowing gastric emptying, and the glucagon arm raises energy expenditure and burns liver fat, so phase 2 trials showed lower blood glucose, 3-5% weight loss, and improved liver-fibrosis markers (PMID 29945727; PMID 34016612). It is given once daily by subcutaneous injection, titrated slowly from 50 mcg up to a 300 mcg maintenance dose to limit nausea. Cotadutide was never approved by any regulator, and AstraZeneca halted the once-daily program in 2023, so it remains research-only. The reconstitution and dosing figures here are an educational reference, not medical advice.
Reconstitute: Add 2 mL bacteriostatic water → 2.5 mg/mL concentration.
Typical dose: 50-300 mcg once daily, titrated (some trials to 600 mcg)
Easy measuring: At 2.5 mg/mL, 1 unit = 0.01 mL = 0.0250 mg (25 mcg) on a U-100 insulin syringe.
Storage: Lyophilized powder stored frozen at −20 °C, protected from light. After reconstitution, store the solution refrigerated at 2-8 °C, do not freeze, and use within approximately 28 days. Discard if cloudy or discolored.
Half-life: Approximately 8 to 11 hours (mean ~8-9 h early studies; 8.5-10.8 h across renal groups), supporting once-daily dosing; Tmax ~4-8 h.
Route: Subcutaneous once-daily injection (clinically the lower abdomen), titrated 50 → 100 → 200 → 300 mcg.
Status: Investigational only; NOT approved by the FDA or EMA. AstraZeneca discontinued the once-daily program in 2023. Research/educational use only.
About Cotadutide
Cotadutide (MEDI0382) is an investigational, lipidated peptide that functions as a balanced dual agonist of the GLP-1 and glucagon receptors, developed by MedImmune/AstraZeneca for type 2 diabetes, obesity, and metabolic-associated steatohepatitis (MASH/NASH) [1][2]. Unlike many compounds on this site, its real-world clinical route genuinely is subcutaneous once-daily injection, so the reconstitution figures below mirror how it was actually dosed in trials. It is not, however, an approved medicine: AstraZeneca halted the once-daily program in 2023, so every figure here is educational and research-only [8].\n\nThe defining feature of the Cotadutide dosage protocol is mandatory slow titration. Trials started low at 50 mcg/day to let the gut adapt, then stepped up to 100, 200, and a 300 mcg maintenance dose at roughly weekly-to-biweekly intervals; titrating too fast sharply increases nausea and vomiting [1][3]. This guide models a 5 mg vial reconstituted with 2 mL of bacteriostatic water (2500 mcg/mL, i.e. 25 mcg per insulin-syringe unit) so the small microgram doses map cleanly onto a U-100 syringe: 50 mcg ≈ 2 units, 100 mcg ≈ 4 units, 200 mcg ≈ 8 units, and 300 mcg ≈ 12 units.\n\nFrequency: Once daily, by subcutaneous injection (typically lower abdomen), at a consistent time each day. Cotadutide is not FDA- or EMA-approved and is presented here for educational purposes only.
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 2 mL of bacteriostatic water into a sterile syringe.
Inject the water slowly down the inner glass wall of the 5 mg Cotadutide vial; aim the stream at the side, not directly onto the powder, and avoid forceful spraying.
Gently swirl or roll the vial (do not shake) until the solution is completely clear; this yields a 2500 mcg/mL concentration, equal to 25 mcg per insulin-syringe unit.
Store the reconstituted vial refrigerated at 2-8 °C and draw the prescribed units per dose: 50 mcg ≈ 2 units, 100 mcg ≈ 4 units, 200 mcg ≈ 8 units, 300 mcg ≈ 12 units on a U-100 syringe.
Inject subcutaneously into the lower abdomen, rotating sites; insert at the recommended angle, deliver slowly, and wait a few seconds before withdrawing. Follow the slow titration schedule rather than starting at the maintenance dose.
Interactive Cotadutide Syringe Calculator
Currently visualizing the 5 mg vial reconstituted with 2 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 5mg dry powder in 2mL water yields 2.50 mg/mL. To evaluate a 250mcg dose, pull to 10.0 units (10 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) |
|---|---|---|
| Titration start (about weeks 1-2) | 50 mcg | 2 units (0.02 mL) |
| Step-up (about weeks 3-4) | 100 mcg | 4 units (0.04 mL) |
| Step-up (about weeks 5-6) | 200 mcg | 8 units (0.08 mL) |
| Maintenance / therapeutic | 300 mcg | 12 units (0.12 mL) |
Administration guidelines: Refer to guidelines | 2 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 5 mg vial.
Peptide Vials (Cotadutide, 5 mg each):
- check8 weeks at the 300 mcg/day maintenance dose ≈ 4 vials (titration phases use less)
- check12 weeks at 300 mcg/day ≈ 5-6 vials
- check16 weeks at 300 mcg/day ≈ 7 vials
- checkA reconstituted 5 mg vial supplies ~16 days at 300 mcg/day, within the ~28-day refrigerated shelf life
Insulin Syringes (U-100):
- checkOnce-daily dosing: 7 syringes per week
- check8 weeks ≈ 56 syringes; 12 weeks ≈ 84 syringes; 16 weeks ≈ 112 syringes
- checkDoses are small (2-12 units at 25 mcg/unit), so a low-volume U-100 syringe improves accuracy
Bacteriostatic Water (30 mL bottles): Use 2 mL per vial for reconstitution.
- check8 weeks (~4 vials) ≈ 8 mL ≈ 1 bottle
- check12 weeks (~6 vials) ≈ 12 mL ≈ 1 bottle
- check16 weeks (~7 vials) ≈ 14 mL ≈ 1 bottle
Alcohol Swabs: Clean the vial stopper and injection site before each dose.
- checkAbout 2 swabs per daily injection (vial top + skin) ≈ 14 per week
- check8 weeks ≈ 112 swabs; 12 weeks ≈ 168 swabs; 16 weeks ≈ 224 swabs
- checkOne 200-count box covers roughly a 12-16 week course
Mechanism of Action (MOA)
Cotadutide is a synthetic 30-amino-acid peptide derived from oxyntomodulin, an endogenous gut hormone that naturally engages both the GLP-1 and glucagon receptors. To create a drug-like molecule, chemists truncated the oxyntomodulin sequence, substituted several residues to tune receptor balance and resist DPP-4 degradation, and attached a palmitic-acid chain (via a gamma-glutamate linker) to a lysine side chain. This lipidation lets the peptide bind circulating albumin, slowing renal clearance and extending its action enough to support once-daily dosing [2][7].\n\nThe therapeutic concept is to combine two complementary hormone actions in one balanced molecule. The GLP-1 receptor arm stimulates glucose-dependent insulin secretion from pancreatic beta cells, suppresses inappropriate glucagon release, delays gastric emptying, and acts on hypothalamic appetite centers to reduce food intake, driving lower postprandial glucose and weight loss [1][2]. The glucagon receptor arm, which most GLP-1-only drugs lack, increases energy expenditure and promotes hepatic lipolysis, fat oxidation, and glycogenolysis, which is thought to underlie cotadutide's pronounced reductions in liver fat and fibrosis markers [3][6]. Glucagon alone would tend to raise blood sugar, but the simultaneous, dominant GLP-1 insulinotropic effect offsets this, so net glycemic control improves rather than worsens [2]. Stable-isotope studies confirmed the glucagon component is pharmacologically active in humans, increasing endogenous glucose production via glycogenolysis [6].\n\nPharmacokinetics: Cotadutide is administered subcutaneously (clinically into the lower abdomen) and displays approximately linear, dose-proportional kinetics across the 20-600 mcg range. After a single dose, peak plasma concentration is reached at a median time-to-maximum (Tmax) of roughly 4 to 8 hours, and the terminal elimination half-life is about 8 to 11 hours, with a mean near 8 to 9 hours in early studies and 8.5 to 10.8 hours across renal-function groups [4][5]. This half-life, combined with albumin binding, supports a once-daily regimen with steady-state accumulation. Clearance is modest (roughly 0.7-1.0 L/h) and is not meaningfully altered by renal impairment, so no dose adjustment for kidney function was indicated in PK bridging work [4].\n\nBecause GLP-1-mediated slowing of gastric emptying and central appetite effects build over time and drive the dose-limiting nausea, the protocol relies on gradual up-titration from 50 mcg rather than starting at the 300 mcg therapeutic dose. Simulations indicated that biweekly two-fold escalation balances reaching the target dose quickly against keeping nausea rates tolerable [3].\n\nRegulatory note: cotadutide's real route is subcutaneous, so the reconstitution scheme here matches its clinical use, but it is an investigational compound only. It was never approved by any regulator, and AstraZeneca discontinued the once-daily development program in 2023 in favor of a once-weekly GLP-1/glucagon co-agonist [8]. All figures on this page are educational, not medical advice.
Clinical Trial Efficacy Highlights
- starAmbery and colleagues (2018, Lancet) ran a randomized, double-blind, ascending-dose and phase 2a study of MEDI0382 (cotadutide) in obese or overweight adults with type 2 diabetes; over 41 days of once-daily subcutaneous dosing titrated to 200-300 mcg, glucose AUC0-4h after a mixed meal fell significantly versus placebo (LS mean −32.78% vs −10.16%, p<0.0001) and body weight dropped more than placebo (−3.84 kg vs −1.70 kg, p=0.0008) [1].
- starParker and colleagues (2020, J Clin Endocrinol Metab) reported mechanistic phase 2a data showing cotadutide titrated from 50 to 300 mcg produced a −21.52% change in glucose AUC versus +6.32% for placebo (p<0.001), a −3.41% body-weight reduction versus −0.08% (p=0.002) with 42% of treated patients losing at least 5% of body weight, and a dose-dependent delay in gastric emptying time [2].
- starNahra and colleagues (2021, Diabetes Care) conducted a 54-week randomized phase 2b study in 834 adults with overweight/obesity and type 2 diabetes; at week 14, HbA1c fell by roughly 1.1 to 1.3 percentage points across the 100, 200, and 300 mcg arms, and at week 54 cotadutide 300 mcg achieved about 4.34% placebo-adjusted weight loss compared with 2.65% for the open-label liraglutide comparator [3].
- starIn the same 54-week phase 2b study, cotadutide 200 mcg and 300 mcg significantly reduced the FIB-4 fibrosis index versus placebo (p=0.032 and p=0.004) and lowered other hepatic biomarkers, supporting the rationale for testing cotadutide in metabolic-associated steatohepatitis (MASH/NASH) [3].
- starParker and colleagues (2023, Nature Metabolism) used stable-isotope tracer methods to demonstrate that cotadutide engages the glucagon receptor in humans, increasing endogenous glucose production through glycogenolysis, confirming that the molecule's dual mechanism is pharmacologically active rather than GLP-1 effects alone [6].
- starAmbery and colleagues (2018, Br J Clin Pharmacol) established in a single-dose, healthy-subject, randomized phase 1 study that MEDI0382 met its primary safety and tolerability endpoints and showed approximately dose-proportional pharmacokinetics, providing the early evidence base for once-daily subcutaneous titration [5].
- starKlein and colleagues (2023, Clin Pharmacokinet) found in a single-dose phase 1 bridging study that cotadutide exposure and half-life (mean t1/2 8.5-10.8 hours) were not clinically meaningfully altered by renal impairment, indicating no renal dose adjustment was needed in the studied range [4].
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 dose-limiting and the most common: in the 54-week phase 2b study nausea occurred in about 35% and vomiting in about 17% of cotadutide-treated participants, with event rates declining over time as patients adapted [3].
- warningNausea, vomiting, diarrhea, decreased appetite, and constipation are driven mainly by GLP-1-mediated slowing of gastric emptying; escalating the dose too quickly markedly worsens these symptoms, which is why slow titration from 50 mcg is essential [1][3].
- warningBecause the glucagon component transiently raises endogenous glucose production via glycogenolysis, careful dosing and the dominant GLP-1 insulinotropic effect are needed to keep net glycemic control favorable rather than worsening blood sugar [2][6].
- warningAs with other incretin agents, there is risk of hypoglycemia when combined with insulin or sulfonylureas; injection-site reactions and increased heart rate have also been reported with GLP-1-based therapies.
- warningDehydration from vomiting or diarrhea can stress the kidneys; although PK was unchanged in renal impairment, fluid status should be monitored, particularly during titration [4].
- warningGLP-1 receptor agonists as a class carry label warnings for pancreatitis, gallbladder disease, and (in rodents) thyroid C-cell tumors; long-term safety of cotadutide specifically was never fully established because development was halted [3][8].
- warningCotadutide was studied only under medical supervision with structured titration and monitoring; self-directed use of research material carries unverified purity, dosing, and contamination risks.
- warningRegulatory/research status: Cotadutide is NOT approved by the FDA, EMA, or any regulator for any indication. AstraZeneca discontinued the once-daily program in 2023, and the compound remains investigational and for research use only [8].
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 Cotadutide dosage?expand_more
In clinical trials, the typical Cotadutide dosage was a once-daily subcutaneous injection titrated slowly upward: starting at 50 mcg/day, then stepping to 100 mcg, 200 mcg, and a 300 mcg maintenance dose, usually at weekly to biweekly intervals. Some studies escalated further to 600 mcg under safety monitoring. The slow titration is essential to limit nausea and vomiting. These figures are educational only; cotadutide is investigational and never received regulatory approval.
Is Cotadutide FDA approved?expand_more
No. Cotadutide (MEDI0382) is NOT approved by the FDA, the EMA, or any other regulator for any indication. It reached phase 2/3 testing for type 2 diabetes, obesity, and MASH/NASH, but AstraZeneca discontinued the once-daily development program in 2023 to focus on a once-weekly GLP-1/glucagon co-agonist. It remains an investigational, research-only compound, and the information here is educational, not medical advice.
What is the half-life of Cotadutide?expand_more
Cotadutide has a terminal elimination half-life of roughly 8 to 11 hours, reported as about 8 to 9 hours in early phase 1 work and 8.5 to 10.8 hours across renal-function groups. A palmitic-acid side chain lets the peptide bind albumin, slowing clearance enough to support once-daily subcutaneous dosing. Peak plasma levels (Tmax) are reached around 4 to 8 hours after injection.
How do you reconstitute Cotadutide?expand_more
For this educational model, draw 2 mL of bacteriostatic water and inject it slowly down the inside wall of a 5 mg vial, then gently swirl (never shake) until clear. This gives 2500 mcg/mL, or 25 mcg per unit on a U-100 insulin syringe, so 50 mcg is about 2 units, 100 mcg about 4 units, 200 mcg about 8 units, and 300 mcg about 12 units. Store the reconstituted vial refrigerated at 2-8 °C and use within about 28 days.
Can Cotadutide be stacked with other peptides?expand_more
There are no clinical data supporting stacking cotadutide with other peptides, and as an unapproved investigational drug it was only studied as a stand-alone once-daily agent under medical supervision. It already combines GLP-1 and glucagon activity in one molecule, so layering it with other GLP-1 agonists, insulin, or sulfonylureas could amplify gastrointestinal effects and hypoglycemia risk. Combining research compounds is not advised and is outside any studied protocol.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Cotadutide, plus the universal dosing calculator.
Academic References & Study Citations
Ambery P, Parker VE, Stumvoll M, et al. MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study. Lancet. 2018;391(10140):2607-2618. View Scientific Paper →
Parker VER, Robertson D, Wang T, et al. Efficacy, Safety, and Mechanistic Insights of Cotadutide, a Dual Receptor Glucagon-Like Peptide-1 and Glucagon Agonist. J Clin Endocrinol Metab. 2020;105(3):803-820. View Scientific Paper →
Nahra R, Wang T, Gadde KM, et al. Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study. Diabetes Care. 2021;44(6):1433-1442. View Scientific Paper →
Klein G, Petrone M, Yang L, et al. Pharmacokinetics and Safety of Cotadutide, a GLP-1 and Glucagon Receptor Dual Agonist, in Individuals with Renal Impairment: A Single-Dose, Phase I, Bridging Study. Clin Pharmacokinet. 2023;62(6):881-890. View Scientific Paper →
Ambery PD, Klammt S, Posch MG, et al. MEDI0382, a GLP-1/glucagon receptor dual agonist, meets safety and tolerability endpoints in a single-dose, healthy-subject, randomized, Phase 1 study. Br J Clin Pharmacol. 2018;84(10):2325-2335. View Scientific Paper →
Parker VER, Hoang T, Schlichthaar H, et al. Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes. Nat Metab. 2023;5(12):2086-2093. View Scientific Paper →
Cotadutide. Wikipep — The Peptide Encyclopedia (structure, oxyntomodulin derivation, lipidation, development). View Scientific Paper →
AstraZeneca to terminate once-daily cotadutide program to focus on weekly GLP-1RA co-agonist. Pharmaceutical Technology, 2023. View Scientific Paper →