Nature Medicine trial links pasteurized Akkermansia supplement to less weight regain after dieting

A randomized trial published May 12 in Nature Medicine found that adults who took a daily capsule of pasteurized Akkermansia muciniphila MucT after an eight-week low-energy diet regained less weight over a 24-week maintenance phase than those who took a placebo, and preserved insulin sensitivity better ^[3][4]. In a separate trial reported the same day, Eli Lilly said people who switched from injectable Wegovy or Zepbound to oral Foundayo kept most of their earlier weight loss after a year ^[1][2].

The Akkermansia trial was led by Maastricht University and collaborators and enrolled 90 adults with overweight or obesity. All participants first followed an eight-week low-energy diet; those who lost at least 8% of their body weight entered the 24-week maintenance phase, receiving either the pasteurized bacterium or a placebo alongside a healthy, unrestricted diet ^[3]. Outside experts described the design as sound: randomized, double-blind and placebo-controlled ^[4].

Danone Research, which published a summary of the trial, said participants taking the supplement regained "on average about three kilograms less" than the placebo group ^[3]. One of the independent experts described a smaller difference. José Pablo Miramontes González, an internal medicine consultant at Río Hortega Hospital in Valladolid, Spain, put the gap at "approximately 2 kg during the maintenance phase" ^[4]. Both figures refer to the same 24-week period.

The study also reported better preserved insulin sensitivity in the supplement group ^[3]. The largest benefits appeared in participants who had low levels of Akkermansia in their gut at the start, who also saw favorable changes in blood pressure ^[3]. Analyses of fat tissue showed reduced inflammatory signaling and more activity in pathways related to energy metabolism ^[3]. Kieran Tuohy, professor of energy metabolism and microbiome at the University of Leeds, noted the trial also found more energy in participants' stool, a possible clue to how the bacterium works ^[4]. Hormones that regulate hunger and energy intake, including GLP-1, showed little difference between groups, he said ^[4].

Experts listed limits. The trial was small, short and run in a highly selected population, and it did not compare the supplement with any approved obesity medicine, Miramontes said ^[4]. There was no active bacterial comparator, so the benefit cannot be firmly tied to a specific component of Akkermansia ^[4]. Tuohy called the study period short and said a better placebo might have given stronger confidence in the result, though he described both points as minor ^[4]. Miramontes said the findings should be read as a proof of concept, "not as definitive evidence to change clinical practice" ^[4]. It has not been reported whether the supplement is approved or sold in the United States.

A second maintenance trial, in people leaving injectables

Lilly said ATTAIN-MAINTAIN and SURMOUNT-MAINTAIN were presented at the 33rd European Congress on Obesity and published in Nature Medicine and The Lancet ^[1]. In ATTAIN-MAINTAIN, 376 adults who had reached a weight plateau on injectable Wegovy (semaglutide) or Zepbound (tirzepatide) in an earlier study were randomly assigned to once-daily oral Foundayo (orforglipron) or placebo for 52 weeks ^[1][2]. Those who switched from Wegovy maintained all but 0.9 kg of their earlier weight loss on average, and those who switched from Zepbound maintained all but 5.0 kg, Lilly reported ^[1]. Lilly said switchers kept 82.4% and 78.0% of their prior loss ^[1]; the Nature Medicine abstract reports model-based estimates of 74.7% versus 49.2% with placebo in the tirzepatide cohort and 79.3% versus 37.6% with placebo in the semaglutide cohort, both with P<0.001 ^[2]. In SURMOUNT-MAINTAIN, people who stayed on Zepbound at their maximum tolerated dose maintained all of their prior weight loss on average, while reducing the dose to 5 mg maintained all but 5.6 kg ^[1]. Side effects in the Foundayo trial were mostly gastrointestinal and mostly mild to moderate ^[2]. The trial had no arm that continued injectable therapy, and it ran one year ^[2].

Why it matters for patients

Weight regain after stopping a weight-loss treatment has been documented across treatment types, which is why maintenance has become a focus of obesity research ^[2]. Lilly's trial tested one option: moving from a weekly injection to a once-daily pill ^[1][2].

The Akkermansia trial tested something different, a non-drug approach started after diet-based weight loss. Because hunger hormones such as GLP-1 did not change meaningfully in that study, the benefit does not appear to run through the same pathway as GLP-1 medicines ^[4]. Experts described the effect as modest and said the supplement should be seen as a possible complement to obesity drugs, not a replacement for them ^[4]. The trial measured maintenance of lost weight, not weight loss ^[3][4].

What happens next

Researchers say future work will examine longer-term outcomes, interactions with diet, and whether microbiome profiling can identify who benefits most ^[3]. Tuohy said longer mechanistic studies in humans are needed to show how the bacterium works ^[4]. The Akkermansia trial is registered as NCT05417360 ^[3].