Study participants lost more than 24% of their starting weight during a 48-week trial on a new weight loss drug, retatrutide, according to drugmaker Lilly’s news release on June 26, 2023. Weight-loss medications for obesity and type 2 diabetes are so popular that three drugs similar to retatrutide — Wegovy, Mounjaro, and Ozempic — have recently been in short supply.
Drugmaker Lilly announced in June 2023 that a new drug called retatrutide helped study participants lose 24% within a year.
Though still awaiting FDA approval, retatrutide claims to treat obesity, diabetes, and fatty liver disease by helping patients lose weight, reduce blood sugar levels, and lower fatty acids in their liver.
Clinical trials suggest that retatrutide may be the most effective drug yet to help patients tackle obesity, type 2 diabetes, and fatty liver disease.
Like any medication, there are benefits, side effects, and risks to consider before taking retatrutide.
As clinical trials progress, Lilly expects retatrutide to be the most effective drug for obesity and type 2 diabetes. Here’s what to know about retatrutide, its safety, and who can take it.
What is retatrutide?
Retatrutide is a new medication to treat obesity, diabetes, and fatty liver disease. Created by the pharmaceutical company Lilly, retatrutide is an experimental drug heading toward phase 3 of clinical trials.
Lilly recently announced remarkable results from phase 2 of the trial, revealing better success than similar drugs.
During the trial phase, people with obesity who took the highest dose in the study lost an average of 17.5% of their starting weight after nearly six months — halfway through. By week 48, subjects lost more than 24% — an average of 58 lbs.
In addition, nearly all 338 adult participants who took lower doses of retatrutide saw a 5%–15% weight reduction. This is significant because many healthcare providers recommend losing 5% to 10% of one's weight over six months to improve blood pressure, cholesterol levels, prediabetes, and metabolic syndrome.
Unsurprisingly, in their June 26, 2023 news release addressing retatrutide trial results, Lilly announced improvements in blood pressure and blood glucose, cholesterol, and insulin levels at weeks 24 and 48 of the trial.
These results make retatrutide the winner among similar drugs. In 2022, another Lilly drug, Mounjaro (tirzepatide), demonstrated 22.5% weight loss after 72 weeks. Previous studies testing semaglutide (Wegovy, Ozempic) showed 15% weight loss in 24 weeks for people with obesity.
Retatrutide works in three ways
Like Wegovy, Mounjaro, and Ozempic, retatrutide helps people lose weight and lower their blood sugar levels. However, Lilly's clinical trials also demonstrated a powerful third outcome with retatrutide. Results showed significant improvement in non-alcoholic fatty liver disease (NAFLD), a common and dangerous problem for people with obesity and metabolic syndrome.
Because retatrutide works in three ways, it is considered a "tri-agonist."
1. Helps lower blood sugar
Retatrutide helps address obesity and type 2 diabetes by stimulating insulin release and reducing the release of glucagon (a hormone that increases blood sugar). With more insulin in the blood and less glucagon, blood sugar levels drop, which supports weight loss. Ozempic and Wegovy (semaglutide) work the same way.
2. Promotes weight loss
Retatrutide and Mounjaro double the weight loss action of semaglutide by adding a second weight loss mechanism. Both drugs help suppress appetite and prevent fat accumulation, a benefit neither Ozempic nor Wegovy offer.
3. Improves fatty liver disease
After 48 weeks of treatment during Lilly's phase 2 of clinical trials, 9 out of 10 patients with NAFLD showed normal amounts of fat in their liver, effectively resolving their fatty liver disease in the short term. This remarkable effect is groundbreaking because 24% of Americans have NAFLD, and no FDA-approved treatments currently exist. Unchecked, NAFLD can lead to liver damage, failure, or cancer.
Surprisingly, to reduce liver fat, retatrutide stimulates the production of glucagon. As noted above, glucagon increases glucose, but it also helps eliminate fat in the liver. At first, this kick in glucagon levels sounds counterproductive. Scientists have yet to understand why fully, but when combined with its two other mechanisms, retatrutide lowers blood sugar levels and excess fatty acids in the liver.
With its impressive weight loss, blood sugar results, and ability to improve fatty liver disease, retatrutide may help many people overcome obesity, type 2 diabetes, NAFLD, and metabolic syndrome.
Is retatrutide safe?
Phase 2 of the clinical trials found similar safety outcomes and side effects as Wegovy, Mounjaro, and Ozempic. Generally, the side effects worsen at higher doses, but it will take time to verify retatrutide's long-term safety thoroughly.
Retatrutide's side effects
So far, the most common side effects of retatrutide are gastrointestinal, including:
At higher doses, researchers stated these symptoms were "mostly mild to moderate in severity" and typically treated by lowering the dosage. However, 7% of patients also experienced skin tingling. At 24 weeks of treatment, patients' heart rates on higher doses peaked but declined afterward.
Risks of taking retutratide
As with every medication, patients and their providers weigh the risks and benefits of treatment. For some patients, the drug's benefits outweigh the risks. The following are several concerns to consider if contemplating taking retatrutide.
Weight gain after completing treatment
One concern of dieticians is whether patients will regain their weight after completing retatrutide treatment. Ozempic and Wegovy research found that some individuals regained two-thirds of their weight within a year after stopping the medication. Researchers have yet to study this risk for Mounjaro or retatrutide.
These drugs don't address lifestyle changes
Due to the risk of regaining weight, specialists recommend that patients on weight loss drugs make lifestyle changes to keep the weight off. Similarly, without lifestyle changes, a healed liver may become fatty again for patients with NAFLD.
Potential risk for disordered eating
If one loses weight without lifestyle changes, there is a risk of disordered eating, like binging, after treatment. Focusing on mental health wellness alongside lifestyle changes often creates longer-lasting changes for patients. Studies show that disordered eating and chronic health issues are deeply rooted in mental and spiritual wellness, as defined by finding meaning and inner peace.
The drug treats obesity, not minor weight loss
It's tempting to ask a doctor for a pill or injection to help lose 10 lbs. However, since medications come with health risks, retatrutide is for those who have serious health issues related to obesity, making the risks of the medication worth the benefit. For those who are not obese but want to lose weight, the good old fashion way of changing one's diet and exercise is recommended by experts.
Increased risk of pancreatitis
In clinical studies for Mounjaro, a small number of patients experienced acute pancreatitis, a painful inflammation of the pancreas, the organ that releases insulin and glucagon. Most pancreatitis resolves with treatment, but one attack may increase the chances of more in the future. Those at risk for pancreatitis should consider discussing this with their provider before starting a medication like retatrutide or Mounjaro.
Increased risk of thyroid cancer
The scientific community is currently studying whether drugs like retatrutide may increase the risk of thyroid tumors.
On May 8, 2023, The European Medicines Agency (EMA) released a drug safety signal to recommend further study on the possible risk of thyroid cancer from drugs like Ozempic and Wegovy. However, safety signals do not confirm a direct relationship to an adverse drug event. Instead, the goal is to determine whether there is a direct link between a medication and a reported adverse event or new study.
Scientists are debating whether a recent study showing a possible increase in thyroid tumors was accurate and well-designed. They're also debating whether providers inaccurately overdiagnose thyroid cancer and whether lower doses of drugs like Ozempic and Wegovy are the simple answer for reducing possible risks.
Overall, no conclusive evidence exists that medications like retatrutide increase the risk of thyroid tumors, but scientists are concerned enough to recommend studying it further.
Is retatrutide the weight loss savior?
For those facing relentless, health-damaging obesity, retatrutide may be a short-term hero to help them lose weight and improve health while pursuing other long-term solutions. According to doctors and nutritionists, patients must pair drugs like retatrutide with lifestyle changes that include exercise, diet, and inner wellness for long-term health and well-being.
In the meantime, Lilly is still completing its research, and retatrutide won't be ready for FDA approval for many months. People seeking treatment for obesity, type 2 diabetes, metabolic syndrome, or fatty liver disease should talk with their health provider about current treatment options and lifestyle changes.
- Eli Lilly and Company. News Release: Lilly's phase 2 retatrutide results published in The New England Journal of Medicine show the investigational molecule achieved up to 17.5% mean weight reduction at 24 weeks in adults with obesity and overweight.
- The New England Journal of Medicine. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial.
- Journal of Diabetes Investigation. Glucagon regulates lipolysis and fatty acid oxidation through inositol triphosphate receptor 1 in the liver.
- The Lancet. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA.
- The New England Journal of Medicine. Pancreatic Safety of Incretin-Based Drugs — FDA and EMA Assessment.
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- European Medicines Agency. PRAC recommendations on signals.