Latest / The Staple Line / Vol. 2, No. 16: Retatrutide for sleep apnea, reflux and surgical risk, and cancer after surgery

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Vol. 2, No. 16: Retatrutide for sleep apnea, reflux and surgical risk, and cancer after surgery · The Staple Line

• 0:00
  [on-hold music] Hey, welcome back to The Staple Line, the weekly audio edition of MBS Digest.
• 0:17
  I'm John Scott. Now, just in case you were curious, what does MBS stand for? Well, we've changed the name, and MBS now stands for Metabolic and Bariatric Sciences.
• 0:28
  The name of the digest and the name of this show kind of stays the same, The Staple Line. This is Volume two, Issue sixteen.
• 0:36
  This week, a retatrutide trial in sleep apnea, whether reflux before surgery says something about complication risk, what an international position statement says about cancer after surgery and what it doesn't, and two long-term looks at bones and mood after the operation.
• 0:54
  A few numbers on who pays for all of this and a preview of a big Thursday. Same deal as always. I'll keep the numbers light. I'll tell you which findings are actually solid, and the details are in the issue.
• 1:06
  So let's get into it. This week's highlighted article is about sleep apnea, and it's from the New England Journal of Medicine. It reports two randomized trials of retrutide.
• 1:17
  It's Eli Lilly's weekly injection in adults with overweight or obesity and sleep apnea. One trial was in people without diabetes and one with people with type two diabetes.
• 1:29
  About seven hundred people in all followed for about eighty weeks. Lilly funded both of these trials. In the people without diabetes, the two top doses cut breathing interruptions by more than thirty events an hour.
• 1:42
  Placebo cut them by about ten. And since you'll hear this word a lot, statistically significant means unlikely to be a fluke. It doesn't mean big, and it doesn't mean it matters in practice. I'll try to tell you both.
• 1:56
  In that group, the gap versus placebo was statistically significant, and it was big, about twenty-four events an hour.
• 2:04
  In the diabetes trial, the drop was smaller, about twenty-five events an hour versus ten with the placebo. Side effects overall were more common on the drug side on both trials, mostly stomach-related.
• 2:17
  But serious side effects weren't. About eight percent of those on the drug and about ten percent on the placebo in each trial. Now the catch.
• 2:27
  Those headline numbers are what the authors call hybrid treatment estimates, a particular way of handling people who stop treatment. The intention to treat results were similar, and these are sleep study gains.
• 2:40
  The trials didn't measure long-term cardiovascular benefit, so this doesn't tell us about that. [on-hold music] Now to surgery research. Four items. First, reflux.
• 2:58
  An analysis of the MBSAQIP registry looked at more than one point two million patients treated from two thousand and fifteen to two thousand and twenty-two. About three in ten patients had reflux recorded before surgery.
• 3:13
  After adjustment, reflux tracked with modestly higher early complications, such as infections, serious complications, and readmission within thirty days. For infection, the adjusted odds were about a quarter higher.
• 3:28
  Now the catch. This is early morbidity, not the long-term reflux outcomes we usually argue about when we compare operations.
• 3:36
  And it's an observational registry, so it can't separate an effect of reflux itself from other differences in patients who have it. Now a disclosure. Our board member, Phil Schauer, is a co-author of this article.
• 3:50
  Second, cancer. IFSO, our international federation, put out a position statement on cancer incidence after surgery. It pulled together twenty-six studies, and none of them were a randomized trial.
• 4:04
  Compared with non-surgical care, breast cancer was about fifteen percent lower, colorectal nearly thirty percent lower, and endometrial cancer was about sixty percent lower.
• 4:15
  Now, all three of these were statistically significant. But IFSO rates the certainty of the evidence as low to very low because of selection biases and differences between studies.
• 4:26
  And no single estimate rested on more than seven studies. So the position is conditional. Cancer reduction is a plausible extra benefit for patients who already qualify for surgery on metabolic grounds.
• 4:39
  It does not support surgery solely for cancer prevention. And these are relative differences. They don't tell any one patient about their absolute benefit, and they don't prove surgery caused the drop.
• 4:51
  Third, mental health. A scoping review of two hundred and fifty-one studies describes psychological recovery after surgery as uneven over time.
• 5:01
  Depression and anxiety improved most in the first year, and then the gains were smaller or partly reversed. Benefits and burdens could show up in the same patient. Thirty-seven of these studies describe both.
• 5:15
  The severe outcomes in this literature included suicide, self-harm, and alcohol use disorder. The point is that a good average can hide patients whose symptoms persist or get worse.
• 5:27
  So psychological recovery is its own outcome. It can't be assumed from weight loss. A scoping review doesn't pool risk or test anything, so there's no significant or not here.
• 5:38
  And it can't show that surgery caused those trajectories. Fourth, let's talk about bones. A prospective cohort of seventy-two people followed a median of nine years after a sleeve, mostly women.
• 5:53
  Weight fell from about two hundred and fifty pounds to about two hundred. Bone density at the femoral neck in the hip dropped, and that was statistically significant. The lumbar spine, the change wasn't
• 6:06
  The bone changes didn't correlate significantly with changes in weight, BMI, fat, or lean mass. Here's the catch. It's a small cohort and bone density isn't fracture risk, which this study didn't measure.
• 6:21
  But the hip and spine behave differently, which argues against treating bone as one uniform outcome. [outro music] Now, in obesity science, we have three items.
• 6:37
  First, a safety review of GLP-1 drug that sorts effects by how well-supported they are.
• 6:42
  The most consistent one are stomach side effects, a modest increase in gallbladder and biliary disease, and small increases in heart rate. Pancreatitis remains a concern, but the findings conflict.
• 6:56
  And the authors put vision problems, psychiatric symptoms, aspiration, and cancer in a less settled category. Their overall read is a favorable benefit-to-risk balance.
• 7:08
  The caution is that reporting bias and confounding weaken those emerging signals, and a long list of reported events is not the same as a list of established complications.
• 7:20
  It is a narrative review, so there's no test to report. The second study, a systematic review of twenty-five studies, about four thousand adults asking a simple question. Do GLP-1 treatments reduce how much people eat?
• 7:36
  On average, yes, and that was statistically significant. But the effect varied a lot from study to study.
• 7:42
  Only four of the twenty-five were at low risk of bias, and the range you'd expect in a new setting includes no effect.
• 7:50
  And the measure is a standardized difference across different ways of measuring intake, so it isn't a number of calories a day. Third, how about joints?
• 8:00
  A review argues that obesity-related joint damage may outlast the weight loss through inflammatory and epigenetic changes.
• 8:08
  It summarizes a semaglutide trial of about four hundred people over sixty-eight weeks, where pain scores improved by about forty-two points on the drug versus twenty-eight on the placebo.
• 8:20
  The issue gives no test for that comparison, so I won't call it. The review's own framing is that persistent pain after weight loss need not mean the weight loss had no value.
• 8:30
  But the mechanism rests largely on experimental models, and pairing weight loss with treatments aimed at those changes hasn't been clinically validated.
• 8:38
  [outro music] Now we've got a preview for this upcoming week, and it's a good one. On Thursday, October twenty-ninth at six in the morning Eastern, The Staple Line has its first guest interview.
• 8:56
  My guest is Dr. Adrian Dan of Summa Health, Professor of Surgery at Northeast Ohio Medical University, and a member of the ASMBS Board of Directors.
• 9:05
  We talk about where metabolic and bariatric surgery stands today, from his childhood in Romania, Algeria, and Germany, to the question of who will lead the next model of metabolic care. Dr. Dan's disclosures.
• 9:18
  He's a proctor and instructor for Intuitive Surgical, a shareholder and key opinion leader for Fractal Health, and founder and director of National Surgery Review.
• 9:27
  He took part in his own capacity, not on behalf of Summa Health or any other institution, entity, or society.
• 9:35
  Also, the Digest will publish on Thursday an editorial from board member Phil Schauer on the ARMS type two diabetes study, which followed about two hundred and sixty adults with type two diabetes and obesity for up to fourteen years after random assignment to surgery or medical lifestyle therapy.
• 9:54
  The editorial will look at what the study's predictors of remission and relapse mean when surgery is considered. Disclosure, Dr. Schauer is also a co-author of that study.
• 10:05
  A majority of the board's voting editors approved the editorial for publication. [outro music] In the marketplace this week, there are three items. It's all about money.
• 10:20
  First, a modeling study on what happens if more people with obesity get treated. It simulated about forty-seven million commercially insured adults who had no diabetes or cardiovascular disease at baseline.
• 10:34
  Over five years, it projected roughly ten billion dollars in medical savings and about twenty-six billion in workplace benefits.
• 10:44
  Put the medical, disability, and productivity gains together, and they recover about eighty percent of the direct treatment cost.
• 10:52
  Add a dollar value for better quality of life and lower mortality, and the model represents a society return of a bit over two dollars for every dollar that's invested.
• 11:02
  But that's societal value, not a cash surplus for health plans. The comparison is with current treatment patterns, not universal treatment, and the side effect costs are only partially modeled.
• 11:15
  It's a projection, so there's no significant or not. Disclosure.
• 11:20
  Several of those authors work for Global Data, which consults for obesity treatment manufacturers and other authors are American Diabetes Association employees.
• 11:32
  Second, AstraZeneca announced an AI drug discovery deal with Insitro for MASH and cardiomyopathies. Forty million dollars up front and nearly one and a half billion in milestones.
• 11:44
  That ceiling isn't committed spending, and this comes from AstraZeneca's own press release and it reports no patient outcomes, so it can't tell us about efficacy, safety, or faster development.
• 11:55
  It matters for obesity-related liver disease, but it's discovery work, not treatment. And third, Intuitive Surgical reported their earnings.
• 12:04
  The company reported about s-- fourteen percent growth in worldwide da Vinci procedures last quarter and four hundred and fifty million dollar charge for an antitrust settlement agreed in October without admission of liability or wrongdoing.
• 12:18
  Court approval is still pending. More than half of the new systems were placed on operating leases, many of those with usage-based terms, which ties part of the platform's business to procedural volume.
• 12:30
  And the procedure numbers cover all specialties, so that can't really tell us about bariatric volume or patient outcome. Now before I go, one thing.
• 12:45
  The MBS Digest runs on what this community sends in, and the submissions page is open at mbsdigest.com slash submit. This week, I'm especially curious about practice tours.
• 12:56
  So show us your program, your clinic, or your OR. And interview ideas. Dr. Dan is our first guest, so tell me who should be next and why now.
• 13:07
  You can also send in an article suggestion, a commentary of 600 to 900 words, a letter to the editor, 200 to 400 words, a practice spotlight, or even a poll question. Two ground rules.
• 13:20
  Disclose any industry relationships because we publish them with a piece and keep patient information out of it. The editorial board reviews every submission, and I'll write back either way.
• 13:31
  That's thembsdigest.com slash submit, and the link is in the show notes. Well, I hope you've enjoyed the staple line for issue 16. Every source is linked in the show notes, and the full issue is free at mbs-digest.com.
• 13:46
  Remember, this is a summary of published evidence, not medical advice. I'm John Scott. Thanks for listening, and please come back Thursday for Dr. Adrian Dan.