If you're overweight or you have obesity, losing 5% to 15% of your body weight can improve your heart health and lower your risk of type 2 diabetes. But losing weight can be hard to do. If diet and exercise haven't helped you reach a healthy weight and stay there, prescription weight loss drugs might help.
The FDA has already approved a group of weight loss drugs called GLP-1 receptor agonists. Medicines like liraglutide (Saxenda), semaglutide (Ozempic, Wegovy), and tirzepatide (Mounjaro, Zepbound) act like the hormone glucagon-like peptide in your body. They slow digestion and make you feel less hungry to help you lose more weight. These drugs also lower blood sugar levels to treat type 2 diabetes.
Following the success of GLP-1 agonists, a new generation of weight loss drugs is coming down the research pipeline. Some are pills, which may be easier to take than the current injected drugs. Others work in different ways from the GLP-1 drugs.
A few weight loss drugs are in phase III trials. Phase III is the last phase of research before a drug company can ask the FDA for approval to market the medicine. Before a drug gets to phase III, it must go through a small phase I trial (20 to 100 people) to see if it's safe and what the recommended dosages might be. Then it goes through a slightly larger phase II study (100 to 300 people) to see how well it works. Researchers will also track any reported side effects.
Phase III studies can last for a few years. During this time, researchers will still be looking at how well the drug works, as well as following up on any bad reactions that people taking part might have. Some of the drugs listed below may come to market in the next few months or years. Others won't get approved at all. Coming up behind them are many more new weight loss drugs that are in different stages of development.
Cagrilintide and Semaglutide (CagriSema)
CagriSema combines the GLP-1 receptor agonist semaglutide with cagrilintide, a drug that acts like the blood sugar-controlling hormone amylin. Researchers are testing CagriSema as a treatment for overweight and obesity in people with and without type 2 diabetes.
What does CagriSema do?
CagriSema contains two medications that work in different ways. Semaglutide is a GLP-1 receptor agonist. It helps your pancreas release more insulin, a hormone that moves sugar (glucose) from your blood into your cells. It also makes your stomach empty more slowly, so it takes longer for you to feel hungry again. Cagrilintide acts like a hormone called amylin that your pancreas releases. Amylin also lowers your blood sugar levels and makes you feel full faster after you eat.
How is CagriSema different from other obesity treatments?
CagriSema combines two types of medicine in one. It acts like GLP-1 and amylin. This combination is being studied to see if it can improve weight loss.
How is CagriSema taken?
CagriSema is a shot you get under the skin once a week.
Where is CagriSema in the research pipeline?
CagriSema is in phase III clinical trials to see if it improves weight loss. The studies are set to be completed in 2025 and 2026.
CagriSema study results
A phase II study tested the safety and effectiveness of CagriSema in 92 adults with type 2 diabetes who were also overweight or had obesity. They got CagriSema, semaglutide alone, or cagrilintide alone. The main outcome the researchers were studying was hemoglobin A1c levels, a marker of blood sugar control in diabetes.
A1c levels did improve more with CagriSema than with the other medicines. People who took CagriSema also lost more weight than those who took either semaglutide or cagrilintide. Some people had mild side effects in their gut like nausea and vomiting from the drug. But most side effects went away quickly.
A review of studies compared the effectiveness of CagriSema and 14 other GLP-1 drugs. Researchers looked at 76 studies that together included more than 39,000 people who were followed for at least three months. CagriSema led to more weight loss than any other GLP-1 drug. People who took this drug lost an average of almost 31 pounds.
What’s next?
If CagriSema has positive results in phase III trials, the drug’s maker may ask the FDA for approval to market it.
Ecnoglutide (XW003)
Ecnoglutide is a GLP-1 agonist. It's a treatment for overweight, obesity, and type 2 diabetes.
What does ecnoglutide do?
Ecnoglutide works like other GLP-1 drugs. It stimulates insulin release from the pancreas to lower blood sugar levels. Ecnoglutide also slows stomach emptying to help you feel fuller and reduce your appetite.
How is ecnoglutide different from other obesity treatments?
Ecnoglutide is made from natural amino acids. This makes it easier to produce than semaglutide, which is made through a multi-step process using recombinant DNA technology. Ecnoglutide also works in a slightly different way than other drugs in its class. It uses a molecule that helps cells communicate called cyclic adenosine monophosphate (cAMP). cAMP boosts the signals that trigger insulin release and slow stomach emptying.
How is ecnoglutide taken?
It comes as a shot you take once a week.
Where is ecnoglutide in the research pipeline?
A phase III study is looking at the safety and effectiveness of ecnoglutide in people who are overweight or obese. The trial is set to finish in early 2025. A pill version of ecnoglutide is being tested in a phase I study.
Ecnoglutide study results
In a phase II study, researchers randomly divided 145 adults with type 2 diabetes into four groups. The groups received 0.4 milligram (mg), 0.8 mg, or 1.2 mg of ecnoglutide or a placebo once a week for five months. The main outcome that the researchers were testing was A1c, which improved in all three of the groups that took ecnoglutide.
Weight loss was a secondary outcome in the study. The groups that took ecnoglutide lost weight, and the biggest weight loss was in the group that took the 1.2-mg dose. Around 33% of people in that group lost 5% or more of their starting weight. Only 3% of people who took a placebo lost that much weight. Fasting blood sugar levels and low-density lipoprotein ("bad") cholesterol levels also improved in the treatment groups.
The most common side effects with ecnoglutide were:
- Diarrhea
- Nausea
- Constipation
- High cholesterol
- Appetite loss
- Low blood sugar
The study authors say ecnoglutide is as safe as currently approved GLP-1 drugs.
A longer phase III study tested the safety and effectiveness of ecnoglutide. The study included 211 adults with type 2 diabetes. Researchers divided them into three groups. One group got a 0.6-mg injection of ecnoglutide once a week. The second group got a 1.2-mg injection weekly. The third group got a placebo.
After six months, the researchers put all the people in the study on 0.6 mg or 1.2 mg of ecnoglutide for the rest of the study. At the end of one year, more than 43% of those who took the 1.2-mg dose had lost 5% or more of their starting weight. Their A1c numbers also improved.
What’s next?
Ecnoglutide is in phase III studies for overweight, obesity, and type 2 diabetes. Whether it eventually gets approved depends on the results of those studies.
Mazdutide
Mazdutide is both a GLP-1 agonist and a glucagon receptor agonist. It works in two ways to promote weight loss in people who are overweight or have obesity.
What does mazdutide do?
Mazdutide works in two ways. The GLP-1 agonist makes your body release more insulin to lower your blood sugar levels, and it keeps food in your stomach to help you stay full longer. The glucagon receptor agonist works like the hormone glucagon. It makes your liver release more glucose to raise your blood sugar level when it gets too low, helps you feel fuller, and makes your body burn more fat.
How is mazdutide different from other obesity treatments?
The GLP-1 agonist and glucagon receptor agonist work together to keep your blood sugar steady, make you feel full on less food, and help you burn more calories. The combination of these effects might help you lose more weight than a GLP-1 agonist would alone.
How is mazdutide taken?
Mazdutide comes as a shot under the skin. You get it once a week.
Where is mazdutide in the research pipeline?
Five phase III studies of mazdutide are underway. These trials are looking at how well the drug works in adults with overweight, obesity, and type 2 diabetes.
Mazdutide study results
A phase I study of mazdutide included 24 adults with overweight or obesity. After three months, people who took a 6-mg dose once a week lost, on average, about 6% of their body weight. Those who took a 9-mg weekly dose lost almost 12% of their weight.
In a phase II trial, researchers randomly assigned 248 people who were overweight or had obesity to get one of three once-weekly doses of mazdutide – 3 mg, 4.5 mg, or 6 mg – or a placebo.
After six months, the results were:
- People on the 3 mg dose lost almost 7% of their body weight.
- People on the 4.5 mg dose lost more than 10% of their body weight.
- People on the 6 mg dose lost more than 11% of their body weight.
- People on the placebo lost 1% of their body weight.
The most common side effects reported in the study were belly pain, diarrhea, nausea, and vomiting. One person dropped out of the study, and 10 people dropped to a lower dose of mazdutide because of side effects. A couple of people had abnormal results on tests of liver and pancreas function, and a few had a fast heart rate.
In another phase II study, mazdutide helped adults with type 2 diabetes lose up to 7% of their body weight over a 20-week period. People who took this medicine also lowered their A1c levels.
Early results from a phase III study called DREAMS-2 showed that mazdutide helped adults with type 2 diabetes lose more weight and achieve better blood sugar control than Trulicity, according to the drugmaker.
What’s next?
Five phase III studies are underway in adults who are overweight, have obesity, or have type 2 diabetes. The results of these studies will determine whether the drug's maker requests FDA approval.
Oral Semaglutide (Orforglipron)
Orforglipron is a GLP-1 agonist. It's an oral version of the injectable drug semaglutide that helps improve weight loss in adults with obesity. Orforglipron is also a treatment for type 2 diabetes.
What does oral semaglutide do?
Like Ozempic and other GLP-1 agonists, orforglipron helps your pancreas release more insulin. It also slows the rate that food leaves your stomach to keep you feeling full longer.
How is oral semaglutide different from other obesity treatments?
The other GLP-1 agonists come as a shot. Oral semaglutide is different because it's a pill.
How is oral semaglutide taken?
You take oral semaglutide by mouth once a day.
Where is oral semaglutide in the research pipeline?
A phase III clinical trial is comparing the safety and effectiveness of orforglipron with insulin glargine, a treatment for type 2 diabetes. The study has enrolled more than 2,700 people who are overweight or have obesity and have type 2 diabetes. It should be completed in 2025.
Oral semaglutide study results
Studies have shown that oral semaglutide helps people lose more weight than a placebo. It also improves blood sugar control in those with type 2 diabetes.
In a phase I study, researchers assigned 51 people to take orforglipron and 17 to take a placebo. After 12 weeks, the orforglipron group lost up to 13 pounds, compared to 1 pound in the placebo group.
A phase II study included 272 people who either had obesity or were overweight with at least one weight-related condition. Researchers divided the people in the study into five groups. The first four groups got 12 mg, 24 mg, 36 mg, or 45 mg of oral semaglutide every day. The fifth group got a placebo. After nine months, people in the treatment groups lost between 9% and 15% of their starting body weight. The placebo group lost about 2% of their weight.
In another phase II study that included adults with diabetes, orforglipron helped people lose more weight (an average of 22 pounds) after 26 weeks than a placebo (5 pounds) or Trulicity (9 pounds). Orforglipron also improved A1c levels better than the other treatments.
The most common side effects reported in studies were:
- Nausea
- Vomiting
- Constipation
- Diarrhea (at higher doses)
- Gastroesophageal reflux
- Reduced appetite
What’s next?
Orforglipron is in phase III studies to see how well it works in people who are overweight, or who have obesity or type 2 diabetes. The results of this research will determine whether it eventually gets approved.
Retatrutide
Retatrutide is called a triple-hormone-receptor agonist. It works on three receptors in the body to promote weight loss. It's a treatment for overweight, obesity, and fatty liver disease.
What does retatrutide do?
This new obesity drug acts like three hormones: glucose-depending insulinotropic polypeptide (GIP), GLP-1, and glucagon. It helps you feel full after eating less and regulates blood sugar levels to help you lose more weight.
How is retatrutide different from other obesity treatments?
Most other obesity treatments work only on GLP-1, or on GLP-1 plus glucagon. Retatrutide acts in three ways to promote weight loss.
How is retatrutide taken?
Retatrutide is given as a shot under the skin once a week.
Where is retatrutide in the research pipeline?
Phase III studies of retatrutide are in progress. A study called TRIUMPH-1 will look at the safety and effectiveness of this drug in people who are overweight and have obesity, including some people with knee osteoarthritis or obstructive sleep apnea. Another trial will see how well retatrutide works in people with obesity and diseases of the heart and blood vessels. Those studies are set to wrap up in 2026.
Retatrutide study results
Retatrutide has helped people with overweight and obesity lose weight and control their blood sugar better than Mounjaro and Zepbound. In a phase I study of 72 people with type 2 diabetes, people who took 12 mg of retatrutide a week lost an average of nearly 20 pounds, or 10% of their starting weight. This medicine also reduced A1c levels.
A phase II study included 338 adults with a body mass index (BMI) of 30 or higher, or a BMI of 27 to 30 plus at least one weight-related health condition. Researchers divided people in the study into groups and gave each group one of four doses (1 mg, 4 mg, 8 mg, or 12 mg) of retatrutide or a placebo. After one year, the 8 mg and 12 mg groups had lost an average of 23% to 24% of their body weight. The placebo group lost less than 2% of their body weight. Retatrutide also improved cholesterol and blood pressure levels.
Retatrutide helped with metabolic dysfunction-associated steatotic liver disease (MASLD) in another phase II study. MASLD is a buildup of fat in the liver that affects some people with obesity. After one year on retatrutide, more than 85% of people with obesity reduced their liver fat so much that they were no longer considered to have MASLD.
The most common side effects reported with retatrutide in studies included:
- Nausea
- Vomiting
- Diarrhea
- Constipation
Lowering the dose helped to reduce these effects.
What’s next?
Researchers are studying retatrutide's effects on weight loss in phase III trials. Whether this drug eventually gets approved depends on the results of those studies.
Survodutide
Survodutide is a GLP-1 and glucagon agonist. It's a treatment for overweight or obesity, with or without type 2 diabetes and diseases of the heart and blood vessels.
What does survodutide do?
This medicine acts like GLP-1 and glucagon in your body. It helps to control blood sugar and make you feel full sooner so that you eat less.
How is survodutide different from other obesity treatments?
Survodutide works in two ways: as a GLP-1 and glucagon agonist. It helps you eat less and burn more calories at the same time so that you lose more weight.
How is survodutide taken?
Survodutide is a once-weekly shot given under the skin.
Where is survodutide in the research pipeline?
Phase III studies are looking at whether survodutide can improve weight loss in people who are overweight or have obesity, with or without type 2 diabetes and diseases of the heart and blood vessels. It's also being investigated as a treatment for metabolic dysfunction-associated steatohepatitis (MASH). (This condition used to be called nonalcoholic steatohepatitis (NASH)). MASH is a buildup of fat in the liver, along with liver swelling and damage. These studies will be finished in 2026.
Survodutide study results
In studies, survodutide helped people lose more weight. It also improved liver fat in people with MASH.
A phase II study that was done in 12 countries looked at the effects of different survodutide doses (0.6 mg, 2.4 mg, 3.6 mg, or 4.8 mg) in people who were overweight and those with obesity. After 46 weeks of treatment, people who took survodutide lost an average of 6% to 15% of their body weight. The higher the dose, the more weight they lost. People who got a placebo lost less than 3%, on average, of their starting weight.
In people with type 2 diabetes, survodutide may improve both weight loss and A1c levels. A phase II study of adults with type 2 diabetes showed that after 16 weeks on treatment, survodutide led to greater reductions in A1c and weight than Wegovy or a placebo. More than half of people who were treated with a high dose (1.2 mg or more, twice a week) lost 5% or more of their starting weight, and over 25% lost 10% or more of their starting weight.
Researchers have also looked at survodutide as a treatment for MASH. A phase II study compared survodutide to a placebo in 293 people with MASH. More people who took survodutide had improvements in MASH and less liver fat than those who got a placebo.
The most common side effects in studies of survodutide were:
- Nausea
- Diarrhea
- Vomiting
- Heartburn
- Belly pain
- Fast heart rate
What’s next?
The FDA has granted survodutide "fast track" status, according to the drug's maker. To get this status, studies must show that a drug works better than current medicines in its class and that it doesn't have any serious side effects. Being fast-tracked allows a drug to move through the approval process faster. It's not clear when survodutide might get approved.
VK2735
VK2735 is a GLP-1 and GIP agonist. It's being studied as a treatment for obesity.
What does VK2735 do?
The drug helps you feel full more quickly to help you lose weight.
How is VK2735 different from other obesity treatments?
VK2735 is both a GLP-1 agonist and a GIP agonist. It works in two ways to reduce appetite, lower blood sugar levels, and promote weight loss.
How is VK2735 taken?
VK2735 comes as a shot that you get under the skin. It's given once a week. A pill version of the drug is also in development.
Where is VK2735 in the research pipeline?
The injected version of the drug has finished a phase II trial with promising results. The company hopes to move it into a phase III study next. A phase II study of the oral version of VK2735 is expected to start in late 2024.
VK2735 study results
The phase II VENTURE trial looked at the safety and effectiveness of VK2735 for reducing weight. It included 176 people who had either obesity or overweight with at least one weight-related disease. People in the study were given one of four VK2735 doses (2.5 mg, 5 mg, 10 mg, or 15 mg) or a placebo. After 13 weeks on the drug, people lost up to 15% of their body weight, according to the drugmaker. Up to 88% of people who got the treatment lost 10% or more of their body weight, compared with 4% of those who got a placebo.
A phase I study of an oral version of the drug also showed promising results. In the 28-day study, 45 people were randomly assigned to take one of five VK2735 doses (2.5 mg, 5 mg, 10 mg, 20 mg, or 40 mg daily) or a placebo. More than half of people who took the drug lost at least 5% of their body weight. The higher the dose, the more weight they lost. No one in the placebo group lost that much weight.
Most of the side effects reported in the studies were mild and included:
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Reduced appetite
These side effects usually appeared when people first started the treatment and got better with time.
What’s next?
Based on positive phase II study results, the drugmaker plans to meet with the FDA and talk about next steps for VK2735. An oral version has completed a phase I trial, and the company said it was planning to put it into phase II trials in 2024.
