Say goodbye to the "yo-yo effect"! Eli Lilly (LLY.US) has developed a combination of oral weight loss medication and gut microbiome supplements to combat weight rebound.

As millions of people use the new generation of potent weight loss drugs to lose weight, almost everyone is asking the same question: what's next? The latest research results show that people have more choices in combating the frustrating "yo-yo effect" (weight regain after weight loss), including potential benefits from an unassuming probiotic supplement. According to two studies released by the weight loss drug giant Eli Lilly on Wednesday, while drugs are still the best way to maintain weight stability, some patients may be able to reduce their dosage or switch to oral weight loss drugs. Another smaller but insightful trial found that a bacterium called Akkermansia muciniphila (AKK bacteria) can help people who have lost weight through dieting maintain some of their weight loss results. Researchers assessed whether patients could reduce the intensity of treatment to some extent while still maintaining weight loss effects. This issue is crucial for the millions of people who are looking for a new balance and are uncertain about whether they are willing to take potent prescription drugs for life. Dr. Louis Aronne, director of the Comprehensive Weight Control Center at Weill Cornell Medical College, said, "We need to provide people with more choices so that they don't feel trapped." Louis Aronne is also an advisor to Eli Lilly and was involved in leading a trial where patients switched from the injectable weight loss drug Zepbound to Eli Lilly's newest GLP-1 oral weight loss drug, Foundayo. Louis Aronne and other doctors have long compared obesity treatment drugs to blood pressure medications or cholesterol-lowering drugs - the effect can only be maintained through continuous use. However, in the real world, many patients stop taking the drugs in the first year, leading to gradual weight regain and the disappearance of other health benefits. Additionally, because users are uncertain about when to stop the medication, the true cost of obesity treatment drugs is steadily rising. In a study, Eli Lilly provided patients who previously used their injectable weight loss drug Zepbound or the competing drug Wegovy from Novo Nordisk A/S Sponsored ADR Class B with the oral weight loss drug Foundayo. Data showed that patients who switched from Zepbound to Foundayo regained an average of 5 kilograms (11 pounds) of weight a year later, while patients who previously used Wegovy only regained an average of 0.9 kilograms. Louis Aronne suggested that this difference may be due to the stronger weight-loss effects of Zepbound itself, while the mechanism of action of Foundayo is more similar to Wegovy. In another trial involving only Zepbound the study was published in The Lancet Eli Lilly reduced the drug dosage for patients to a lower level. The results showed that these patients regained an average of 5.6 kilograms of weight a year later, while patients on high-dose treatment maintained their weight loss results. Both studies had placebo groups, with patients in these groups regaining weight more quickly. However, since Eli Lilly allowed volunteers to re-medicate six months after regaining half of the weight they lost previously, the comparison between the different groups became more complex. The third study was conducted by a Dutch research team and published separately in the journal Nature Medicine. Patients underwent an eight-week diet in which 84 out of 90 participants lost at least 8% of their body weight. Afterwards, this group returned to a healthy but normal diet for six months. Half of them took a daily dose of pasteurized AKK bacterial supplement a bacterium usually less common in obese individuals and they only regained about 14% of the weight they lost through dieting on average. The other half who took a placebo regained about one-third of their weight loss on average. Although the overall weight loss was lower than prescription weight loss drugs, the group taking the AKK bacterial supplement still weighed 3.1 kilograms less on average than at the start of the study. Researchers found that about 40% of users of gut microbiome supplements continued to lose weight after the diet phase. The study also found that individuals who originally had fewer of these bacteria in their bodies regained less weight after taking the supplement. Additionally, researchers measured that these individuals excreted more energy through feces. Professor Ellen Blaak, who led the study at Maastricht University, stated that unlike obesity drugs, patients taking gut microbiome supplements did not experience additional side effects. She said there is no reason for overweight and obese populations not to try this method. The AKK bacterial supplement used by the research team is currently available in Belgium, the Netherlands, Luxembourg, and Italy, with a monthly cost of around 50 euros ($59). Dr. Francisco Jesus Gomez Delgado, head of internal medicine at Hahnemann University Hospital in Spain, said that although the study was small in scale and its conclusions are not final, it "confirmed that the gut microbiota is a true therapeutic target with potential." Other doctors suggested that gut microbiome supplements could be used in combination with GLP-1 class weight loss drugs. Dr. Deborah Horn, director of the McGovern Center for Obesity Medicine and Metabolic Performance at the University of Texas McGovern Medical School, said, "I would encourage patients to take probiotics." She previously led a low-dose Zepbound trial, but was not involved in the Dutch study. She said, "Sometimes we try certain methods in clinical practice first, and then realize: 'Oh, we should formally study this.'"