Cotadutide dosage and evidence
Written by Aaron CuhaReviewed Sep 2026
The short answer
Cotadutide is a once-a-day shot that acts on both GLP-1 and glucagon.
Evidence grade for Cotadutide: Strong. The rule: at least two finished studies in people, and at least 1,000 people who took it. The sum on this page: 6 completed trials, 1,221 people given it. A grade counts how much has been done to people, not whether it works.
- People given it
- 1,221
- Human studies
- 6
- Found nothing
- 1
Dose
No human dose established
Amounts that were given in studies sit in Human evidence on this page. None of them is a personal dose.
6 completed trials, 1,221 people given it
No first-hand reports gathered yet. That is a gap in what we have collected, not a finding that nothing has been reported.
Goal pages: Fat loss and metabolism, Ageing and longevity, Heart and circulation, Gut health
In plain English
In plain English, from Aaron
This is how I would explain it to a friend. The evidence, with the numbers, is further down the page.
Cotadutide was a daily shot that worked on two hormone signals, GLP-1 and glucagon. GLP-1 cuts appetite and helps blood sugar. Glucagon works on the liver. AstraZeneca tested it for diabetes, kidney disease and fatty liver. The company stopped in 2023 and said safety was not the reason. It was never approved.
What people take it for
- Lower blood sugar in type 2 diabetes.
- Weight loss.
- Clearing fat out of the liver.
- Protecting the kidneys in diabetes.
What studies in people showed
The biggest study had 834 people with type 2 diabetes, for 54 weeks. Blood sugar and weight fell compared with a dummy shot. The top dose took off more weight than liraglutide, and liver scarring scores got better. In 248 people with kidney disease from diabetes, protein in the urine fell 43.9 to 49.9 percent. In 74 people with fatty liver swelling, liver fat fell 5.0 percentage points more than on the dummy. Smaller studies showed people lost weight because they ate less. No study measured heart attacks, kidney failure or deaths. No large final-stage study was ever done.
What people report
Reports, not study results
The good
- Blood sugar, weight and liver fat all came down in the studies on this page.
The bad
- Nausea hit 35 percent and vomiting 17 percent in the biggest study.
- In the fatty liver study, 91.7 percent on the top dose had side effects, and 16.7 percent quit.
Where these come from: These come from the studies on this page. We have not collected user reports on this one yet.
My bottom line
The maker dropped this drug for what it called strategic reasons, and said safety was not one of them. You cannot get it. In my opinion, its value is showing that glucagon adds something for the liver. Newer drugs carry that idea now.
An opinion, not a finding. I am a coach, not a doctor.
What it has been measured to do
Measured in people
Goals Cotadutide has been tested for in people, biggest studies first. We count only what the studies on this page say, so the real numbers may be higher.
- Blood sugar and insulin1,147 people · 3 studies
- Losing weight899 people · 3 studies · 1 found nothing
- Kidney function248 people · 1 study
- Liver fat and liver health74 people · 1 study
- Gut and digestion65 people · 1 study
- Feeling less hungryno headcount stated · 1 study · 1 found nothing
- Cell energy and mitochondriano headcount stated · 1 study · 1 found nothing
29 of the 36 indexed goals have no study of any kind behind Cotadutide
No study in people, animals or cells on this page reports a result for these. That does not prove Cotadutide does nothing for them. It does mean anything you have heard about Cotadutide and one of these did not come from a study cited here.
Show full evidence
What is Cotadutide?
Cotadutide is a once-a-day shot that acts on both GLP-1 and glucagon. AstraZeneca stopped developing it in 2023. Its own registry entries call the reason strategic pipeline planning, not safety. It leaves mid-stage studies in more than a thousand people with type 2 diabetes, kidney disease and fatty liver inflammation (MASH). It never reached a large final-stage study.
Cotadutide is a lab-made peptide that acts evenly on two hormone receptors, GLP-1 and glucagon. It was a daily shot under the skin. MedImmune, then AstraZeneca, developed it as MEDI0382. The targets were type 2 diabetes with obesity, kidney disease caused by diabetes, and fatty liver with inflammation (once called NASH, now MASH). Its place in history: it was among the first two-in-one drugs to show in people that adding glucagon to a GLP-1 drug changes what happens in the liver. Survodutide, mazdutide, pemvidutide and retatrutide now carry that idea forward.
The human record is large for a drug that never reached a final-stage study. The biggest study, published in Diabetes Care in 2021, ran 54 weeks. 834 adults with type 2 diabetes and a BMI of 25 or more were assigned by chance to cotadutide 100, 200 or 300 mcg a day, a dummy injection, or liraglutide 1.8 mg, which people knew they were getting. Cotadutide lowered average blood sugar (HbA1c) and weight compared with the dummy at weeks 14 and 54, and chance is very unlikely to explain that. At 300 mcg, weight loss beat liraglutide 1.8 mg. Liver enzymes, a blood marker of scarring (propeptide of type III collagen) and scarring scores improved on 300 mcg, but not on liraglutide. Nausea hit 35 percent and vomiting 17 percent. In kidney disease from diabetes (248 people, 26 weeks, Kidney International 2024), protein leaking into the urine fell 43.9 percent at 300 mcg and 49.9 percent at 600 mcg, compared with the dummy. Semaglutide 1 mg was given openly as a reference. The 600 mcg dose was described as about as easy to take as semaglutide. In the PROXYMO study, 74 people had biopsy-confirmed MASH with scarring but not cirrhosis, for 19 weeks. The 600 mcg dose cut liver fat by 5.0 percentage points more than the dummy, and lowered the liver enzymes ALT and AST. The cost: side effects in 91.7 percent against 37.5 percent, and 16.7 percent quit the drug against 4.2 percent. Smaller studies of how it works showed that weight loss came from eating 41 percent less, not from burning more. They also showed cotadutide drains stored sugar (glycogen) from the liver in a way liraglutide does not. That is evidence the glucagon part is working in the human liver.
The programme ended in early 2023. Two early AstraZeneca studies were stopped: a heart rhythm study (31 people) and a study in people with liver damage (24 people). For both, the company wrote the same reason on the ClinicalTrials.gov record. It said it dropped cotadutide for strategic pipeline reasons. It said the early closure was not due to any new safety signal or a change in the balance of risk and benefit. That is the company's own record, and it is the only reason given. Cotadutide was never approved anywhere, and no final-stage study was ever registered.
How does Cotadutide work?
In people, cotadutide's GLP-1 side does the familiar things for this drug family. It boosts insulin after meals, slows how fast the stomach empties, and cuts how much people eat. In a 65 person study, the blood sugar rise after meals fell 21.5 percent, against a 6.3 percent increase on a dummy injection. Insulin after meals rose, and the stomach took about two hours longer to empty half its contents. In a 19 person energy study, weight loss came from eating 41.3 percent less. Energy burned, measured with a gold-standard water test, barely changed. The glucagon side is what set it apart. In a study that scanned the liver, cotadutide cut stored liver sugar (glycogen) after meals and while fasting. It also cut liver fat. Both fell more than on a dummy injection and more than on liraglutide. The researchers read this as glucagon acting directly on the human liver and making it release stored sugar. The rest comes from animals. In animals, switching on the glucagon receptor also raises energy burned and fat burning in the liver. The mouse study most cited for cotadutide's liver effects (Nature Metabolism, 2020) found its weight and blood sugar effects ran mainly through GLP-1. Its effects on liver fat, stored sugar and the cell's energy factories ran through glucagon. At the same weight loss, it cut liver scarring in mice more than liraglutide or obeticholic acid did. That paper is animal work, in mice with fatty liver inflammation. It has been wrongly cited as a human study. It is not one.
What have studies in people found about Cotadutide?
A large mid-stage record and no final-stage study. Studies against a dummy injection in 834 people with type 2 diabetes over 54 weeks, 248 with kidney disease from diabetes over 26 weeks, and 74 with biopsy-confirmed MASH over 19 weeks. Plus several smaller studies of how it works. AstraZeneca paid for all of them. ClinicalTrials.gov lists 23 cotadutide or MEDI0382 studies: 21 finished and 2 stopped when the programme closed.
- 54 week study, 834 people: average blood sugar (HbA1c) and weight lower than on the dummy at 14 and 54 weeks, and chance is very unlikely to explain it. 300 mcg beat liraglutide 1.8 mg on weight. Liver enzymes and scarring scores improved on 300 mcg and not on liraglutide. Nausea 35 percent, vomiting 17 percent.
- Kidney disease from diabetes, 248 people, 26 weeks: protein in the urine down 43.9 percent (300 mcg) and 49.9 percent (600 mcg) compared with the dummy. Kidney filtering (eGFR) was not reported as better. Semaglutide 1 mg was given openly as a reference.
- PROXYMO, 74 people with biopsy-confirmed MASH, 19 weeks: liver fat down 5.0 percentage points at 600 mcg. ALT and AST down. Side effects in 92 percent, and 17 percent quit, on that dose. No second biopsy.
- 65 people, 49 days: blood sugar rise after meals down 21.5 percent, weight down 3.4 percent, stomach emptying slowed.
- People with chronic kidney disease, 41 people, 32 days: blood sugar rise after meals down 26.7 percent, against a 3.7 percent increase. Weight down 3.41 kg against 0.13 kg.
- Energy study, 19 people who finished: weight loss explained by eating 41 percent less. No rise in energy burned was found.
- Liver sugar study: stored liver sugar fell more than on liraglutide, fasting and after meals. That is taken as a sign glucagon is acting in the human liver.
- End of the programme: two early studies stopped in early 2023. The company's registry statement said the reason was strategic, not safety.
What this does not tell you: No study ran longer than 54 weeks, and none measured real health results. No heart attacks or strokes, no kidney failure, no liver biopsy change, no deaths. The MASH study measured liver fat and enzymes, not a second biopsy. People knew when they were on liraglutide or semaglutide, so those comparisons were not blind. The company stopped before any large confirming study, so the mid-stage signals were never tested at scale. The company's stated reason is the only one on record. None of this is evidence that cotadutide does not work. It is evidence that nobody ever took the question to a large final-stage study.
The state of the research
Cotadutide is the clearest case in the GLP-1 family of a drug with good mid-stage results that was dropped for reasons that had nothing to do with those results. AstraZeneca's own registry entries say so in plain words: strategic pipeline reasons, not a safety signal, not a change in the balance of risk and benefit. Trade press at the time linked the decision to the company's newer drugs, and to the once-a-week dosing rivals already had. No primary source states that, and this page reports only what the company recorded. A daily shot entering a final-stage study in 2023 would have faced weekly semaglutide and tirzepatide, and weekly two-in-one drugs like survodutide. That business case had little to do with how the drug worked in the body.
The science it left is real, and it is mostly about the liver. The human data on liver sugar and liver fat came early. So did the 54 week scarring-marker data that set cotadutide apart from liraglutide. Together they were early evidence in people that adding glucagon to GLP-1 does something extra in the liver. Survodutide, pemvidutide and retatrutide are now testing that idea in MASH in large final-stage studies. That is where cotadutide belongs: as the first proof in people for an idea, not as a drug anyone can take. One correction worth recording. The 2020 Nature Metabolism paper often cited for cotadutide's effect on fatty liver inflammation is a mouse study. The human data are in Diabetes Care 2021 and Clinical Gastroenterology and Hepatology 2024.
The evidence, in charts
Fig. 1a · how many people
1,221people, across 4 studies in people cited here
| Study | People | Share |
|---|---|---|
| Diabetes Care 2021 | 834 | 68% |
| Kidney International 2024 | 248 | 20% |
| PROXYMO, Clinical Gastroenterology and Hepatology 2024 | 74 | 6% |
| Journal of Clinical Endocrinology and Metabolism 2020 | 65 | 5% |
One study holds 68% of these people, so the total rests more on one study than its size suggests. Counts are the number of people each study on this page says it signed up. That includes studies that only watched people and gave nobody the compound. 4 more studies in people give no headcount and are not counted here. Studies still signing people up are left out, and only studies cited on this page are counted.
Fig. 1b · evidence mix
8 of 10 sources here are studies in people. The rest are not.
- Study in people · done in people880%
- Animal study · done in animals110%
- Review of studies · sums up other studies110%
Counted from the list of sources on this page. It counts only what we cite, so there may be more studies out there. A review counts once, however many studies it sums up.
Fig. 2 · evidence over time
The studies cover 4 different years, 2020 to 2024, counted from the list of sources on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Not approved
AU
Not approved
CA
Not approved
Not approved in any of the four countries shown. This is what the law says, not a verdict on the science. See Legal status below for the full text and any notes.
Fig. 4 · how much does what
Nobody has tested different amounts in people
This chart would show how the effect changes as the amount goes up. For this compound, nobody has measured that in people. So we leave it empty. We will not borrow an animal chart and pretend it works the same in people.
Fig. 5 · what the molecule is
- Kind of compound
- Peptide
- Molecule weight
- Not on file
- Half-life
- None on file
- Chain length
- None on file
No amino acid sequence is on file for Cotadutide, so none is drawn rather than guessed from a name.
The studies we cite
- Study in people2021Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study
Cotadutide lowered blood sugar and weight in people with diabetes, and it beat liraglutide on weight at the top dose. 834 adults on metformin were split by chance across three doses, a dummy, or liraglutide, for about a year. Blood sugar and weight both fell against the dummy. At the highest dose, liver enzymes and scarring scores improved, which liraglutide did not manage. Nausea hit about a third and vomiting about one in six. AstraZeneca funded it.
834 adults with type 2 diabetes and BMI 25 or more on metformin, randomised to cotadutide 100 mcg (100), 200 mcg (256) or 300 mcg (256), placebo (110) or open-label liraglutide 1.8 mg (110) for 54 weeks. HbA1c and weight fell against placebo at weeks 14 and 54 (all P below 0.001). Weight loss at 300 mcg exceeded liraglutide; liver enzymes and fibrosis scores improved at 300 mcg but not with liraglutide. Nausea 35 percent, vomiting 17 percent. Funded by AstraZeneca (registry NCT03235050, results posted 2020).
- Study in people2024A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease
Cotadutide sharply cut protein leaking into the urine in diabetic kidney disease. 248 people with type 2 diabetes and kidney damage were split by chance across three doses, a dummy, or semaglutide, for about six months. Protein in the urine fell by roughly half at the two higher doses, and the fall held. Serious side effects were balanced across groups. Protein in the urine is a marker, not a kidney that has been saved. Nobody was followed long enough to see kidney failure. The sponsor paid.
248 people with type 2 diabetes and chronic kidney disease (mean eGFR 55, 47 percent on SGLT2 inhibitors), 26 weeks, randomised to cotadutide 100, 300 or 600 mcg, placebo, or open-label semaglutide 1 mg weekly. Urine albumin to creatinine ratio fell 43.9 percent at 300 mcg (95 percent CI 30.6 to 54.7) and 49.9 percent at 600 mcg (38.4 to 59.3) against placebo at week 14, sustained to week 26. Serious adverse events balanced; tolerability at 600 mcg described as comparable to semaglutide. Sponsor funded (NCT04515849, results posted January 2025).
- Study in people2024Safety and Efficacy of Novel Incretin Co-agonist Cotadutide in Biopsy-proven Noncirrhotic MASH With Fibrosis
Cotadutide cut liver fat in people with confirmed liver inflammation, but never looked at the liver itself again. 74 people with biopsy-confirmed disease were split by chance between two doses and a dummy, for about five months. At the top dose, liver fat fell by five percentage points more than on the dummy. Side effects hit nine in ten at the top dose against fewer than four in ten on the dummy. No second biopsy was taken, so nothing is known about scarring. The sponsor paid.
PROXYMO: 74 people with biopsy-proven non-cirrhotic MASH with fibrosis, randomised to cotadutide 600 mcg, 300 mcg or placebo for 19 weeks. At 600 mcg, absolute liver fat fraction fell 5.0 percentage points against placebo (95 percent CI 1.5 to 8.5), ALT fell 23.5 U per L and AST 16.8 U per L. Any adverse event in 91.7, 76.9 and 37.5 percent; discontinuation for adverse events 16.7, 7.7 and 4.2 percent. No histological endpoint. Sponsor funded.
- Study in people2020Efficacy, Safety, and Mechanistic Insights of Cotadutide, a Dual Receptor Glucagon-Like Peptide-1 and Glucagon Agonist
An early trial showed cotadutide blunts the blood sugar spike after a meal, and takes off some weight. 65 adults with diabetes and extra weight took it daily for seven weeks, or a dummy. After meals, blood sugar rose about a fifth less, while it climbed on the dummy. Weight fell about three and a half percent, against almost nothing on the dummy. The stomach emptied roughly two hours more slowly. Seven weeks tells you about the mechanism, not about living with the drug. The sponsor paid.
Phase 2a, 65 adults with type 2 diabetes and overweight or obesity, 49 days of daily cotadutide (50 to 300 mcg) or placebo. Postprandial glucose area under the curve fell 21.5 percent against a 6.3 percent rise on placebo (P below 0.001); weight fell 3.41 percent against 0.08 percent (P equals 0.002); postprandial insulin rose and gastric emptying half-time lengthened by about two hours. Sponsor funded.
- Study in people2024Dual glucagon-like peptide-1 and glucagon receptor agonism reduces energy intake in type 2 diabetes with obesity
People lost weight on cotadutide because they ate less, not because they burned more. This small study followed 12 people on the drug and 7 on a dummy for six weeks. The drug group lost four percent of their body weight against one and a half percent on the dummy. They ate far less food. Energy burned, measured properly, did not change at all. Nineteen people is a very small number for a question this specific. AstraZeneca funded it.
Phase 2a energy balance study; 12 cotadutide and 7 placebo completers over 42 days. Weight change minus 4.0 percent against minus 1.4 percent (P equals 0.011); energy intake fell 41.3 percent against placebo; energy expenditure by doubly labelled water did not differ (1.0 percent, P equals 0.784). Weight loss was driven by eating less, not by burning more. Funded by AstraZeneca.
- Study in people2023Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes
Cotadutide does reach the liver and change how it handles stored sugar. Researchers scanned the livers of people with diabetes and extra weight while they took the drug or a dummy. Stored liver sugar fell on cotadutide, both after meals and while fasting. It fell more than it did on liraglutide, and so did liver fat. The authors read that as proof the drug is acting on the liver. This is about mechanism. It says nothing about whether anyone gets healthier. AstraZeneca funded it.
Two-part randomised phase 2a using magnetic resonance spectroscopy. Cotadutide reduced postprandial (day 28) and fasting (day 35) liver glycogen against placebo, the primary endpoints, and reduced liver glycogen and fat more than liraglutide, which the authors interpret as glucagon receptor engagement in the human liver. Funded by AstraZeneca; several authors are AstraZeneca employees (NCT03555994).
- Study in people2023A Thorough QTC Study to Assess the Effect of Cotadutide on Cardiac Repolarization in Healthy Participants
This heart rhythm study was stopped, and the company says it was not for safety reasons. 31 people had taken part. The sponsor's own words on the record are that it dropped cotadutide for strategic pipeline reasons, and that the early closure was not due to any newly observed safety signal or change in the risk and benefit picture. No results were posted. A programme can end for business reasons and still leave the safety question unanswered.
Phase 1, 31 participants, TERMINATED. Sponsor's why-stopped text: discontinuing the development of cotadutide, a daily injectable GLP-1/glucagon co-agonist, is based on strategic pipeline considerations; the premature closure is not due to any newly observed safety signals or a change in the risk/benefit profile.
- Study in people2023Pharmacokinetics of Cotadutide in Participants With Hepatic Impairment
A second study, in people with damaged livers, was stopped at the same time. 24 people had taken part. The sponsor gave the identical reason on the record: development discontinued for strategic pipeline reasons, not for safety signals and not because the risk and benefit picture changed. No results were posted. This study would have shown how the drug behaves in a liver that does not work properly, and now nobody knows.
Phase 1, 24 participants, TERMINATED March 2023 with the same sponsor statement: development discontinued for strategic pipeline considerations, not for safety signals or a change in the risk benefit profile.
- Review of studies2024Safety and efficacy of GLP-1 and glucagon receptor dual agonist for the treatment of type 2 diabetes and obesity: a systematic review and meta-analysis of randomized controlled trials
This review pooled studies of two drugs of this type, mazdutide and cotadutide: 11 published and 4 unpublished, all against a dummy injection. Average blood sugar (HbA1c) fell 0.63 points and weight fell 4.16 percent. Serious side effects were no more common. But the odds of any side effect were 2.52 times higher, and of vomiting 6.05 times higher. Chinese government science funds paid for it, not either drug maker. It mixes two different drugs.
Pooled analysis of mazdutide and cotadutide placebo-controlled trials (11 published, 4 unpublished): HbA1c minus 0.63 percentage points (95 percent CI minus 0.82 to minus 0.44), body weight minus 4.16 percent (minus 5.41 to minus 2.92); no difference in serious adverse events (OR 1.03) but treatment-emergent adverse events OR 2.52 and vomiting OR 6.05. Funded by Chinese national science foundations, not by either manufacturer. Pools two different molecules.
- Animal study2020Resolution of NASH and hepatic fibrosis by the GLP-1R/GcgR dual-agonist Cotadutide via modulating mitochondrial function and lipogenesis
In mice. In mice with fatty liver inflammation, cotadutide's weight and blood sugar effects came mainly through GLP-1. Its effects on liver fat, stored sugar and the cell's energy factories came through glucagon. At the same weight loss, it cut liver scarring more than liraglutide or obeticholic acid. AstraZeneca staff wrote it. It has been wrongly cited as a human study, and it is not one.
Mouse models of steatohepatitis. Weight, food intake and glucose effects ran mainly through GLP-1 signalling; liver lipid, glycogen flux and mitochondrial effects through the glucagon receptor. Cotadutide reduced fibrosis more than liraglutide or obeticholic acid at matched weight loss. This is animal and mechanistic work with AstraZeneca employee authors; it has been miscited elsewhere as a human randomised trial and is not one.
Where to buy Cotadutide
No seller we track lists Cotadutide yet. We read sellers’ public product lists every week, and this section fills in as soon as one does. Every seller, graded
Common questions
Has Cotadutide been tested in people?
Yes. 1,221 people given it across 6 completed trials cited here, 1 of which found nothing. Cotadutide is a once-a-day shot that acts on both GLP-1 and glucagon.
What is the Cotadutide dosage?
No human dose established. Amounts that were given in studies sit in Human evidence on this page. None of them is a personal dose. 6 completed trials, 1,221 people given it
Is Cotadutide FDA-approved?
Never approved anywhere. AstraZeneca stopped work on it in early 2023, and said it was a business choice about which drugs to pursue (ClinicalTrials.gov NCT05668936 and NCT05517226). No final-stage study was ever registered.
Is cotadutide still in development?
No. AstraZeneca stopped development in early 2023. For two stopped early studies, the company's own ClinicalTrials.gov entries say the decision was based on strategic pipeline reasons. They say it was not due to any new safety signal or a change in the balance of risk and benefit. No final-stage study was ever registered, and it was never approved anywhere.
What did the human trials show?
In 834 people with type 2 diabetes over 54 weeks, cotadutide lowered average blood sugar (HbA1c) and weight compared with a dummy injection. The 300 mcg dose took off more weight than liraglutide 1.8 mg. It also improved liver enzymes and scarring scores, which liraglutide did not. In 248 people with kidney disease from diabetes, it cut protein in the urine by 44 to 50 percent. In 74 people with biopsy-confirmed MASH, it cut liver fat by 5 percentage points, but 92 percent on the top dose had side effects. No study measured real health results such as heart attacks, kidney failure or liver biopsy change.
Why does a discontinued drug matter?
Because its human data were early evidence that adding glucagon to a GLP-1 drug changes what happens in the liver. It cut stored liver sugar and fat in ways liraglutide did not. Survodutide, pemvidutide and retatrutide now carry that idea into large final-stage studies. Cotadutide is the proof of the idea, not a treatment option.
Was it stopped for safety reasons?
Not according to the only primary source. The company wrote in the study registry that closure was not due to new safety signals or a change in the balance of risk and benefit. Its side effects in studies were typical for GLP-1 drugs. Nausea hit about a third of people and vomiting about one in six, and more people quit at the highest doses.