(엠바고 해제 발송) GLP-1 수용체 차단제와 식이요법, 그 후 관리법 전문가 의견 26-054 체중 감량 뒤 ‘요요 현상’ 막을 두 전략 (네이처 메디신)
2026.5.13. **엠바고 13일(수) 07시 해제**
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- 배경
- 주사 치료 또는 식이요법을 통해 감량한 체중을 유지하기 위한 전략이 13일 오전 '네이처 메디신'에 나란히 실립니다. 경구 투여하는 GLP-1 수용체 작용제, 또는 매일 복용하는 유익균 보충제가 과체중 또는 비만 환자의 체중 감량 유지에 도움이 될 수 있다는 내용을 담고 있습니다.
- 첫 논문에서, 미국 코넬대 등 연구팀은 이중맹검, 무작위 배정 3b상 임상시험 결과를 공개했습니다.
- 연구팀은 GLP-1 수용체 작용제인 티르제파티드 또는 세마글루티드 주사 치료를 72주간 완료한 미국인 참가자 376명을 대상으로, 52주 동안 매일 한 번씩 경구 GLP-1 수용체 작용제인 오르포르글리프론 또는 위약을 투여하는 임상시험을 했습니다.
- 그 결과, 티르제파티드 치료 경험이 있는 그룹에서 오르포르글리프론 투여군은 52주 차에 이전 체중 감량의 74.7%를 유지한 반면, 위약 투여군은 49.2%를 유지했습니다.
- 세마글루티드 치료 경험이 있는 그룹에서도 각각 79.3%와 37.6%를 유지했습니다.
- 두 번째 연구에서, 네덜란드 마스트리히트대 연구팀은 네덜란드에 거주하는 과체중 또는 비만 성인 90명을 대상으로 이중맹검 무작위 대조 시험을 실시했습니다.
- 참가자들은 먼저 8주 동안 저칼로리 식단을 통해 체중을 감량했습니다. 이 중 8% 이상 체중 감량에 성공한 84명은 이후 24주 동안 건강한 식단을 유지했습니다.
- 연구팀은 이들을 두 그룹으로 나눴습니다. 한 그룹은 살균 처리된 장내 유익균인 아케르만시아 뮤시니필라(Akkermansia muciniphila Muc T) 보충제를 매일 복용하고, 다른 그룹은 위약을 복용했습니다.
- 그 결과, 유익균 보충제를 복용한 그룹은 1단계에서 감량했던 체중의 13.6%를 다시 찌운 반면, 위약을 복용한 그룹은 32.9%를 다시 찌웠습니다. 보충제를 복용한 그룹은 위약을 복용한 그룹보다 연구 시작 시점부터 총 3.1kg 더 많은 체중 감량을 달성했습니다.
- 종합하면, 1)주사 요법 뒤 오르포르글리프론으로 전환하거나, 2)식이요법을 통한 체중 감량 뒤 장내 미생물군 표적 보충제를 복용함으로써 초기 체중 감량 효과를 유지할 수 있다고 두 연구팀은 주장했습니다.
- 전문가 의견 요청 내용
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내용 해설 (결과에서 흥미롭거나 주목할 부분, 다른 논문이나 기존 논문과와의 차별성 등)
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이번 논문의 의의 또는 한계, 향후 전망과 연구 과제, 임상시험 통계 및 결과 해석 상 주의할 점
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한국에서 특별히 주목해야 할 부분(국내 학계의 관련 연구, 한국 내 관련 연구, 향후 진행하면 좋을 연구 등)
- 국내 전문가 및 해외 SMC 수집 의견을 전달합니다.
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기자 여러분은 아래 주의사항을 참고해 활용해주시길 부탁드립니다.
- 엠바고는 5월 13일 07시(KST) 해제됐습니다. 자유롭게 활용 가능합니다.
- 되도록 원문을 그대로 활용해주시길 부탁드립니다.
- SMCK를 꼭 인용할 필요는 없습니다. 만약 인용 출처가 필요한 경우, 아래 형식을 따를 수 있습니다.
- "ㅇㅇㅇ(전문가)는 한국과학기술미디어센터에 ㅁㅁㅁ라고 말했다."
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이상엽 KAIST 생명화학공학과 특훈교수・연구부총장
*2026.5.13.
(논문 1 관련 의견)
본 논문은 마운자로로 잘 알려진 티르제파타이드나 위고비로 알려진 세마글루타이드 주사 치료로 체중 감량 후 경구용 약인 오르포르글리프론을 52주간 투여한 경우가 위약 대비 감량된 체중을 유의미하게 덜 증가 시켰다는 내용이다. 하지만 체중 조절이라는 것이 1년 하고 말 것이 아니므로 52주가 지난 후에의 중장기 투여/추적 시험과, 오르포르글리프론을 투여하는 대신 주사 치료제를 같은 기간 투여시 어땠는지 대조시험이 빠진 부분은 아쉽다. 또, 논문의 저자 다수가 오르포르글리프론을 개발한 일라이 릴리 직원이거나 자문위원 등이라는 점을 인식하고 읽는 것을 권장한다.
leesy@kaist.ac.kr |
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김필 가톨릭대 생명공학과 교수・헤모랩 대표
*2026.5.12.
논문 1의 오르포르글리프론은 편의성(경구 투여, 상온 보관 등)이 기존 GLP-1 수용체 작용제 대비하여 개선된 합성 물질이며, 신경 교란에 의한 식욕 감퇴로 인한 체중 감량 효과가 임상 결과 유사하다는 의미입니다. 따라서 요요 현상을 원천적으로 막는 새로운 전략이라고 판단되지는 않고, ‘사용 편의성이 증가되면서 기존 GLP-1 수용체 작용제의 대체 약물로서 체중 감량 효과가 임상에서 확인되었다’는 요약이 더 타당하다고 여겨집니다.
논문 2는 건강한 장내세균의 하나인 아커멘시아 균주의 배양 사균체를 복용하여 과체중이 억제됨이 임상으로 확인되었다는 논문입니다. 이 원리는 해당 균주의 사균체가 식품으로써 건강한 장 상태에 의한 체중 감량 유지를 임상 확인한 것이므로, ‘요요 현상을 막을 전략’이라는 타이틀에 더 적합하다고 여겨집니다. 단지, 해당 세균 사균체는 식품이므로 단일 성분인 약물과 달리 복합 성분으로 구성되어서 작동 방식이 복합적이므로 여러 유사한 예제나 예상 작동 방식이 더 많이 축적되도록 연구할 필요가 있다고 보입니다.
국내에서도 최근 새로운 대체 단백질원 식품으로서의 세균 사균체 식이가 동물 실험에서 유사한 효과를 보인다는 결과들과, 그 작동 방식이 보고되고 있습니다. 식품 원료 등재를 위한 국내 행정 과정 이후에 임상시험을 통해 결과가 더 축적될 것으로 기대됩니다.
kimp@catholic.ac.kr |
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아래는 스페인 사이언스미디어센터(SMC Spain)에서 수집한 두 주제의 전문가 반응입니다. 스페인 SMC 홈페이지에서도 확인할 수 있습니다. |
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Cristóbal Morales has only reviewed the study on orforglipron:
Cristóbal Morales, head of the Metabolic Health, Diabetes and Obesity Unit at Vithas Hospital in Seville and a member of the Spanish Society for the Study of Obesity (SEEDO), said:
“This study is very important because it focuses not so much on losing weight, but on maintaining the benefits, something we are currently concerned about. Previous studies showed that stopping medication could lead to a rebound effect if things weren’t done properly. That is why we are very keen to incorporate certain key concepts into obesity therapy that allow us to understand and treat it effectively, such as the fact that, as it is a chronic and complex condition, it requires long-term treatment and sustained support over time. That is why the maintenance phase is so important.
In this trial on orforglipron it is demonstrated and published how strategies based on oral obesity therapy using a small molecule that acts on GLP-1 receptors maintain that benefit over time (52 weeks). It is true that longer studies are needed, but these will surely be reported in due course. This is very good news because what we want is to maintain that benefit. We currently have clinical trials with different alternatives for that maintenance phase”.
Conflict of interest:
“I am a researcher working on orforglipron and with pharmaceutical companies conducting clinical trials in diabetes and obesity, such as Lilly, Novo Nordisk, Amgen, Boehringer and Pfizer”.
José M. Ordovás, a senior researcher at the Jean Mayer USDA Human Nutrition Research Centre on Ageing and a professor of Nutrition and Genomics at the Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, both at Tufts University (USA), said:
“These two trials are significant because they address one of the most challenging phases of obesity treatment: not so much losing weight, but maintaining the weight loss achieved. The orforglipron trial is a phase 3b, randomised, double-blind, placebo-controlled study in people who had previously lost weight with tirzepatide or semaglutide. Its results support the idea that switching from an injectable treatment to an oral GLP-1 receptor agonist may help preserve a substantial portion of the weight loss achieved, which could have important practical implications for treatment adherence, acceptability and scalability. The trial with pasteurised Akkermansia muciniphila is smaller, but also randomised and double-blind, and suggests that targeting the microbiota–metabolism axis could modestly help reduce weight regain following a low-calorie diet, with interesting signals regarding insulin sensitivity and possible differences depending on baseline Akkermansia abundance.
That said, both studies should be interpreted with caution. In the case of orforglipron, the comparator was placebo rather than continued injectable treatment, so it is not possible to conclude whether switching to the oral route is equivalent to continuing with semaglutide or tirzepatide. Furthermore, the follow-up period was one year and the population was from the United States, with limited diversity. In the case of Akkermansia, the sample size was small, the follow-up was 24 weeks after weight loss, and the effects, whilst promising, are modest and require confirmation in longer and more diverse studies. Taken together, the two studies reinforce an important idea: obesity must be understood as a chronic and biologically defended condition, in which maintenance requires sustained strategies. They also point towards a more combined and personalised future, where drugs, nutrition, microbiota, behaviour and individual patient characteristics are integrated to improve the durability of results".
He has not responded regarding whether he has any conflicts of interest.
Francisco Jesús Gómez Delgado, coordinator of the Vascular Risk Unit and head of the Department of Internal Medicine at Jaén University Hospital, associate professor of Medicine at the University of Jaén and member of the Diabetes, Obesity and Nutrition Group of the Spanish Society of Internal Medicine, said:
Article 1: orforglipron
Is this a high-quality study?
“The fact that it is a clinical trial specifically designed for a particular objective ensures the highest possible rigour. Specifically, it is a phase 3b, randomised, double-blind, placebo-controlled trial, with two well-defined cohorts from previous incretin-based treatments, where sample size has been calculated to analyse and demonstrate the primary and secondary endpoints defined for this study”.
What are its limitations?
“The main limitation is that it conducts a head-to-head comparison and does not compare orforglipron with continued treatment with semaglutide or tirzepatide, as was done in the SURMOUNT-5 clinical trial from which these patients were drawn. Furthermore, the study lasts only 52 weeks, which limits our full understanding of its long-term efficacy and safety.”
What are its implications and how does it fit with existing evidence?
“This study reinforces the idea that obesity is a chronic condition requiring a long-term therapeutic approach using the various tools available, including maintenance therapies with orally administered incretins, which are potentially more scalable and acceptable to many patients.”
Article 2: Akkermansia muciniphila pasteurised
Is it a high-quality study?
“This study, as in the previous case, is a randomised, placebo-controlled trial, so we can affirm its methodological robustness for a clinical proof of concept. Furthermore, it incorporates biomarkers and mechanisms of interest in the understanding of metabolic health, such as the gut microbiota, adipose tissue, and lipid and glucose metabolism.”
What are its limitations?
“On the other hand, its sample size is small, the follow-up period is short, and the demonstrated effect on body weight is limited. Furthermore, it does not include other active comparators or biological models that would allow the observed benefit to be confirmed or clarified more precisely.”
What are its implications and how does it fit with existing evidence?
“In this regard, it clearly supports the hypothesis and the role played by our gut microbiota, depending on its profile, in phenomena such as inflammation, dyslipidaemia or diabetes. Likewise, this study identifies the gut microbiota as a genuine therapeutic target in the management of obesity. Furthermore, it is proposed as a complementary tool to supplement pharmacological, nutritional and behavioural strategies, which makes it an interesting option.”
Conflicts of interest:
- Speaker: Ferrer, Amgen, Sanofi, AstraZeneca, Boehringer Ingelheim–Lilly, Janssen, Novo Nordisk, Daiichi Sankyo, Novartis, Rovi and Vifor.
- Advisory board: Amgen and Sanofi.
- Conference invitations: Ferrer, Amgen, Sanofi, AstraZeneca, Boehringer Ingelheim–Lilly, Janssen, Novo Nordisk, Daiichi Sankyo and Rovi.
- Clinical trial investigator: Ferrer, Amgen, Sanofi, Janssen, Novo Nordisk, Daiichi Sankyo, Novartis, Ionis Pharmaceuticals and Boehringer Ingelheim–Lilly.
José Pablo Miramontes González, a consultant in internal medicine at the Department of Internal Medicine at Río Hortega Hospital (Valladolid), said:
“The ATTAIN-MAINTAIN study is a trial of high methodological quality: a phase 3b, randomised, double-blind, placebo-controlled trial in patients who had previously lost weight with tirzepatide or semaglutide within the SURMOUNT-5 trial.
Its main value is that it answers a very clinical question: what happens if, following significant weight loss with an injectable treatment, patients switch to an oral option such as orforglipron to maintain the benefit. The results are consistent and clinically relevant: orforglipron enabled a higher proportion of weight loss to be maintained than placebo, following both tirzepatide and semaglutide, with a safety profile dominated by gastrointestinal effects, generally mild or moderate. However, there are significant limitations: it was not compared against continuing semaglutide or tirzepatide; the population was drawn solely from the United States; it was a selected cohort—patients who had already tolerated and responded to incretins; it did not include patients with diabetes; and the follow-up period was only one year. Furthermore, the use of orforglipron as rescue therapy in the placebo group partially limits a pure long-term comparison. Overall, the study fits very well with previous evidence showing that obesity is a chronic and relapsing condition, and that discontinuing treatment often leads to weight regain. Its most practical implication is that a sequential strategy—potent injectable treatment to induce weight loss followed by maintenance with an oral GLP-1 receptor agonist—could be a realistic alternative to improve adherence, acceptability and scalability, although it does not yet demonstrate that it is superior to continuing the injectable treatment.
The trial with pasteurised Akkermansia muciniphila MucT also has a sound design: randomised, double-blind and placebo-controlled, with an initial low-calorie diet phase followed by a 24-week maintenance phase. The primary outcome is positive: participants treated with Akkermansia regained less weight than those in the placebo group, with a difference of approximately 2 kg during the maintenance phase, and the effect appeared to be greater in subjects with lower baseline abundance of Akkermansia. Furthermore, the study provides interesting mechanistic data on insulin sensitivity, faecal energy excretion, microbiota and gene expression in adipose tissue, making it biologically plausible rather than merely descriptive. That said, caution is warranted: it is a small, short-term study conducted in a highly selected population and without comparison to current anti-obesity drug treatments. The magnitude of the effect is modest and does not allow us to conclude that this intervention is an alternative to incretin agonists, but rather a possible complementary strategy.
Mechanistic questions also remain, as there was no active bacterial comparator or modified strains to allow the effect to be attributed with certainty to specific components of Akkermansia. Therefore, in my view, the study is promising, but it should be interpreted as a clinical and metabolic proof of concept, not as definitive evidence to change clinical practice”.
He has not responded regarding any conflicts of interest.
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아래는 영국 사이언스미디어센터(UK SMC)에서 수집해 배포한 전문가 반응입니다. 영국 SMC 홈페이지에서도 확인할 수 있습니다. |
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Prof Kieran Tuohy, Professor of Energy Metabolism and Microbiome, University of Leeds, said: *추가
· Does the press release accurately reflect the science?
“Yes, the press release gives a fair interpretation of the research article Mount et al.”
· Is this good quality research? Are the conclusions backed up by solid data?
“The study used the randomised controlled trial design, a gold standard in determining cause and effect between ingestion of a test food and an observed health effect. It clearly showed that consuming the pasteurised Akkermansia muciniphilaMucT capsules helped people who had already lost weight following a low-calorie diet for 8 weeks to keep more of the weight off than people taking a control or placebo capsule. This an amazing observation, and an important one given the difficulties people face maintaining body weight after either dieting or successful treatment with GLP-1 RA medications. Indeed, this study strongly suggests that gut health and the interaction between gut bacteria, even dead ones in this case, and the human body is important for maintaining body weight. It raises interesting research questions and possibilities for helping people who have lost body weight after treatment with GLP-1 RA drugs since these people seem to put weight back on quickly once they stop taking these hormonal drugs. The study also observed that the Akk. muciniphila MucT treatment also improved insulin sensitivity and increased energy content of the faeces. These observations give some interesting hints at possible mechanisms of action and are in line with evidence form previous human studies and from mouse experiments but showing how Akk. muciniphila MucT works will need further, mechanistic human studies and over a longer period of time.”
· How does this work fit with the existing evidence around Akkermansia muciniphilaMucT supplementation
“As noted by the authors, a previous study in people with the metabolic syndrome, a condition that leads to type 2 diabetes, showed improvements in metabolic and heart disease risk factors. Similarly, this research group and others have shown that Akk. muciniphila and specifically, a protein (Amuc_1100) on its surface, can reduce inflammation and improve metabolic health markers, including GLP-1, in mouse experiments. Of course, this bacterial surface protein does not need Akk. muciniphila MucT to be alive to have an effect on the host immune system. Although little difference in immune parameters or hormones that regulate hunger and energy intake like GLP-1 were observed in this human study, changes in these parameters may need differently designed human studies. When and where we measure these things can determine whether we can observe changes in response to intake of a test food or drug, for example, how long after ingestion blood samples were collected or whether markers of inflammation were measured in blood or fat tissue may effect our ability to observe changes. Therefore, as highlighted by the authors, further mechanistic studies in humans are needed to uncover how this all works.”
· Have the authors accounted for confounders? Are there important limitations to be aware of?
“By in large yes. The did mention that a better placebo might have provided a stronger confidence in the effect they observed, but in fairness, this is a minor point. The study was only for a fairly short period of time, but the authors too mentioned this as a weakness in their current study. “
· What are the implications in the real world? Is there any overspeculation?
“As mentioned above, this study has implications for how we design dietary strategies to help people who have lost weight after dieting, or increasingly, after successful treatment with GLP-1 RA medications to keep the weight off and prevent the return of poor regulation of blood glucose, a main driver of type 2 diabetes onset. It shows that what happens in the gut does not just stay in the gut but has implications for whole body energy metabolism and disease risk and supports further studies targeting how our gut bacteria interact with our bodies to help in the fight against obesity and the diseases of obesity. “
Dr Marie Spreckley, Research Programme Manager, University of Cambridge, said:
“This is a very clinically relevant study because it addresses one of the biggest unanswered questions in obesity care: how weight reduction can best be maintained after significant weight loss achieved with injectable incretin therapies.
“The findings suggest that switching from injectable semaglutide or tirzepatide to oral orforglipron helped participants maintain a substantially greater proportion of the body weight reduction previously achieved over 52 weeks compared with placebo. This is important because weight regain after discontinuation of incretin-based therapies is well documented and remains one of the major challenges in long-term obesity management.
“One of the most valuable aspects of this study is that it reflects a highly realistic clinical scenario. Many people do not want to remain on injectable therapy indefinitely due to treatment burden, convenience, travel, storage requirements, cost, or personal preference. The possibility of transitioning to an oral therapy while maintaining a substantial proportion of the previously achieved weight reduction could therefore represent an important additional option within longer-term obesity care pathways.
“The study itself was well conducted, using a randomised, double-blind, placebo-controlled design, and the conclusions are generally supported by the data presented. The gastrointestinal side effects observed were also broadly consistent with what we already know about incretin-based therapies.
“However, there are important limitations to consider. The study duration was only one year, so we still do not know how durable these effects will be over longer periods of time. The population was predominantly white and based entirely in the United States, which may limit generalisability. Importantly, there was no comparison group that continued injectable therapy, so this study cannot determine whether switching to oral orforglipron is comparable to remaining on injectable treatment long term.
“Overall, this study reinforces the growing recognition that obesity is a chronic, relapsing disease that often requires ongoing treatment and support. It also highlights the potential future role of oral incretin therapies in creating more flexible and scalable long-term obesity treatment pathways.”
Declared interests
Prof Kieran Tuohy: “I have no professional or personal connection with the authors. I have had research and consultancy (advisory and led or been involved in supported research projects) with many companies e.g. Danone, Pepsico, Coca-Cola, International Flavours and Fragrances, Danisco, Benio, Cereal Partners Worldwide, Novartis, Muller Dairies, Jordens Cereals, Aboca, Melinda, AB Mauri over the years but none of them have inputted into my contribution here. I get the majority of my current funding from UKRI funded projects.”
Dr Marie Spreckley: “Dr Marie Spreckley is a postdoctoral researcher in obesity, nutrition, and behavioural weight management. She has conducted research on incretin-based therapies and nutrition support in obesity care. No relevant competing financial interests to declare.” |
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한국과학기술미디어센터(SMCK) 소개
한국과학기술미디어센터는 근거 기반의 과학 정보를 언론에 제공하는, 과학계와 미디어 사이의 다리 역할을 하는 독립 비영리 조직입니다. 잘못된 정보와 가짜 뉴스가 넘쳐나는 세상에서, 제대로 된 전문가의 해설과 의견을 빠르고 다양하게 기자들에게 제시하고 이를 체계적으로 아카이빙하는 역할을 합니다.
2025년 7월 이사회를 구성하고(이사장 노정혜 전 한국연구재단 이사장) 센터장(이근영 전 한겨레 과학전문기자)을 선임했으며, 같은해 9월 개소식을 열며 활동을 시작했습니다.
*참고 기사:
SMCK 역할
SMCK는 세 분야 전문가인 과학자, 기관 커뮤니케이터(홍보팀), 기자에게 구체적인 도움을 드리고자 설립됐습니다. 각각 아래와 같습니다.
- 과학자, 연구자에게는 의견과 해설이 온전한 맥락과 함께 제공되는 안전한 발언 공간이 돼줍니다. 선의를 위해 한 논평이 기사화 과정에서 왜곡되거나 부정확하게 변질될 우려를 줄이는 완충 작용을 합니다.
- 기관 홍보 담당자에게는 기관의 성과를 기자들에게 보다 객관적이고 정교하게 알리고, SMC 글로벌 네트워크를 통해 영향력을 높일 기회를 제공합니다.
- 기자에게는 사안을 해석하는 데 도움이 될 치우침 없는 종합적인 정보를 빠르고 풍성하게 제공하고, 이를 통해 기사에서 과학과 기술을 보다 자유롭고 편리하게 활용하도록 돕습니다.
SMCK는 이를 통해, 궁극적으로 근거에 기반해 사안을 합리적으로 판단하고 이것이 정책에까지 반영되는 사회를 만드는 데 기여하고자 합니다.
해외 협력
사이언스미디어센터(SMC)는 2002년 영국에서 최초로 설립됐고 현재 호주와 뉴질랜드, 독일, 스페인, 대만, 아일랜드 등으로 확장됐습니다. 한국은 2025년 12월, 7번째 센터로 합류했습니다. 글로벌 네트워크에 포함된 8개 조직은 엄격한 독립성과 신뢰성이라는 가치를 공유하고 있으며 협력을 통해 주요한 국제 과학 이슈에 공동 대응하고 있습니다.
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* 지난 의견은 '지난 의견 다시 보기'를 선택해주세요. |
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내용문의: 윤신영 미디어국장 yoonsy@smck.or.kr
비상 연락(당직 전화): 010-4440-5450
한국과학기술미디어센터(SMCK)
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