Danuglipron and Orforglipron: What to Know About These Next Generation Weight Loss Pills
Key takeaways:
Orforglipron and danuglipron and two “glipron” medications in clinical trials. If the FDA approves them, they’d be oral alternatives to injectable glucagon-like peptide-1 (GLP-1) agonists like Wegovy (semaglutide).
Interim study findings are available for both medications. Orforglipron helped people lose up to 15% of their starting body weight after 8 months. Danuglipron helped people lose up to 9 lbs (4 kg) after 4 months. Their side effects are similar to injectable GLP-1 agonists.
Orforglipron is currently attracting more attention than danuglipron. It’s taken once daily, and it’s on track to finish clinical trials first. Danuglipron is taken twice daily.
Table of contents
There’s always a media buzz when a new weight loss drug hits the market. Or when new data shows that a medication can effectively lower body weight. If weight loss is something that you’re interested in, medication might present a way forward.
If you've been exploring medication options to help you manage your weight, you may have stumbled across injections, such as Wegovy (semaglutide) and Saxenda (liraglutide). For some, the thought of regularly giving yourself injections may seem overwhelming or uncomfortable. Fortunately, a new generation of weight loss pills may soon become an alternative option to injectable glucagon-like peptide-1 (GLP-1) agonists.
What are ‘glipron’ medications?
A promising pair of medications, known as “gliprons,” is being studied in clinical trials for weight loss and Type 2 diabetes. The nickname for these medications comes from their suffixes, or the ending of their generic names.
Save every month on GLP-1 meds with GoodRx
Save an average of $235 on FDA-approved GLP-1s like Ozempic and Zepbound.
Orforglipron is one example. It’s an oral capsule taken once daily. It’s a GLP-1 agonist that has similar effects as other medications of its type. Orforglipron is made by Eli Lilly, the same company that makes Mounjaro, Trulicity (dulaglutide), and many other diabetes medications.
Danuglipron is also in advanced stages of development. It’s a twice-daily oral tablet that works the same way as orforglipron. It’s made by Pfizer, who is also in the process of developing a once-daily extended-release (ER) version of danuglipron.
Good to know: Try not to confuse gliprons with gliptins. Gliptins are a different group of Type 2 diabetes medications. Januvia (sitagliptin) and Tradjenta (linagliptin) are two common gliptins.
How are orforglipron and danuglipron different from other weight loss medications?
Orforglipron and danuglipron are similar to other GLP-1 agonists. But they’re made using different materials and processes.
Injectable GLP-1 agonists, such as Wegovy and Saxenda, are peptides (chains of amino acids) that resemble a gut hormone called GLP-1. This hormone plays a role in digestion and blood glucose (sugar) regulation. These medications mimic GLP-1’s natural effects, helping you feel fuller for longer and curb your appetite. This often leads to weight loss.
But these peptides can’t travel through your stomach very well due to their size. Plus, enzymes (proteins) and acids in your gut can break peptides apart, rendering them ineffective. This is why they’re typically made as injections, not pills.
Orforglipron and danuglipron address this issue. Like many other medications, they’re made using chemicals — not peptides or proteins. They’re able to start working after you swallow a dose. Dubbed “nonpeptide” GLP-1 agonists, they activate GLP-1 in their own way.
As an added bonus, experts predict that orforglipron and danuglipron will be easier and cheaper to produce in bulk. This may translate to additional savings at the pharmacy.
Non-GLP-1 weight loss medications
Other FDA-approved weight loss medications are available. They work in a different way than GLP-1 agonists.
Contrave: This oral tablet contains naltrexone, an opioid blocker, and bupropion, an antidepressant. It reduces cravings and hunger.
Qsymia: This oral capsule also contains two active ingredients. Phentermine is a stimulant and topiramate ER is an anti-seizure medication. Together, they can lessen cravings and hunger.
Orlistat: This oral capsule helps your body absorb less dietary fat. It’s available with a prescription as name-brand Xenical and over the counter as name-brand Alli.
Phentermine: A short-term weight loss treatment, this oral tablet is a stimulant that reduces appetite. Benzphetamine, diethylpropion, and phendimetrazine are alternative options that work in a similar way.
Imcivree: Unlike the other medications, Imcivree isn’t a pill. It’s an under the skin injection that promotes weight loss for those with certain genetic conditions. Its active ingredient is setmelanotide.
Many more medications are taken off-label for weight loss. Metformin, topiramate (Topamax), and bupropion are three options out of many. They tend to cause weight loss as a side effect.
Are there clinical trial results for orforglipron and danuglipron for weight loss?
Yes. Orforlipron and danuglipron are both going through clinical trials. Phase 2 study results are available for both medications.
According to its manufacturer, orforglipron helped adults lose an average of up to 15% of their initial body weight. These results were seen after about 36 weeks (8 months) of daily use. Everyone in the study was considered overweight or obese.
Danuglipron also has positive results. Adults with Type 2 diabetes lost an average of 9 lbs (4 kg) after taking danuglipron twice daily for about 16 weeks (4 months).
Both medications still have work to do. Results from orforglipron’s phase 3 weight loss studies should be available by mid-to-late 2027. Another phase 3 study focusing on people with Type 2 diabetes wraps up earlier, in 2025. If results are positive, an FDA approval application could come next. Plans for danuglipron’s phase 3 studies should be finalized by late 2023.
What are the side effects of orforglipron and danuglipron?
All medications can cause side effects, including orforglipron and danuglipron. So far, clinical studies suggest that orforglipron and danuglipron have similar side effects to injectable GLP-1 agonists. Nausea, diarrhea, and stomach pain are all possible complaints.
We’ll learn more about risks and side effects as clinical trials go on.
What other new weight loss drugs are being developed?
Weight loss medications are a hot topic of research. Many pharmaceutical companies are working on developing weight loss medications in clinical trials. Gliprons aside, other examples include:
Retatrutide: An under-the-skin injection, retatrutide targets three hormones in the body — GLP-1, GIP (glucose-dependent insulinotropic polypeptide), and glucagon. A phase 2 study found it can help people lose up to 24% of their starting body weight.
Oral semaglutide: Under the brand name Rybelsus, this oral GLP-1 agonist is already approved to treat Type 2 diabetes. But it may be approved for weight loss soon, too. It’s thought to have comparable weight loss effects as Wegovy, its injectable counterpart.
APH-012: This once-daily pill mimics the effects of “weight loss surgery,” better known as gastric bypass surgery. It’s currently in a phase 2 study.
ARD-101: This twice-daily oral pill goes after proteins called “bitter taste receptors” in your gut. Phase 2 studies suggest it can lessen how hungry you feel.
The bottom line
Orforglipron and danuglipron are oral gucagon-like peptide-1 (GLP-1) agonists. Unlike injectable GLP-1 agonists, they’re made from chemicals — not peptides. They appear to be effective treatment options for weight loss and Type 2 diabetes, but clinical trials are still underway. Orforglipron is currently on track to obtain FDA approval before danuglipron.
Why trust our experts?
References
Aardvark Therapeutics, Inc. (2023). Aardvark Therapeutics reports positive phase II clinical data for ARD-101. Cision PR Newswire.
American Diabetes Association. (2023). American Diabetes Association highlights novel agent retatrutide which results in substantial weight reduction in people with obesity or Type 2 diabetes during late breaking symposium.
Aphaia Pharma. (n.d.). Programs.
Clinicaltrials.gov. (2023). A study of orforglipron in adult participants with obesity or overweight and Type 2 diabetes (ATTAIN-2). U.S. Department of Health and Human Services.
Clinicaltrials.gov. (2023). A study of orforglipron (LY3502970) in adult participants with obesity or overweight with weight-related comorbidities (ATTAIN-1). U.S. Department of Health and Human Services.
Griffith, D. A., et al. (2022). A small-molecule oral agonist of the human glucagon-like peptide-1 receptor. Journal of Medicinal Chemistry.
Hendricks, E. J. (2017). Off-label drugs for weight management. Diabetes, Metabolic Syndrome and Obesity.
Pfizer. (2023). Pfizer provides update on GLP-1-RA clinical development program for adults with obesity and Type 2 diabetes mellitus.
Saxena, A. R., et al. (2023). Efficacy and safety of oral small molecule glucagon-like peptide 1 receptor agonist danuglipron for glycemic control among patients with Type 2 diabetes. Journal of the American Medical Association, Network Open.
Sidik, S. (2023). Beyond Ozempic: Brand-new obesity drugs will be cheaper and more effective. Nature.
Wharton, S., et al. (2023). Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. The New England Journal of Medicine.
World Health Organization. (2023). Pre-stems: Suffixes used in the selection of INN February 2023.
