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Bariatric surgery - best known treatment for PCOS!

14 March 2025

Hi All,

For patients struggling with the side effects of PCOS on a day-to-day basis, this trial gives some good news.  It proves that Bariatric (weight loss) surgery improves ovulatory function significantly more than non-surgical treatments for PCOS.  Women in this trial who had weight loss surgery were four times more likely to ovulate compared with those who hadn’t had surgery. 

It follows that the final outworking of this biochemical improvement is the up-tick in fertility that most women are looking for.  Anecdotally, in my experience as a Bariatric Surgeon, the ability for women to conceive is similarly improved with the ongoing weight loss that bariatric surgery brings about – I know, because we, at BetterLife Surgery, get to celebrate with our women who have babies after struggling with  infertility due to PCOS for many years.  Not all women will be that lucky, but the significant weight loss surgery can stimulate, is a positive factor that can make pregnancy possible.  Another potential benefit of weight loss surgery!  If you want to talk further – don’t hesitate to contact me.

Happy days!

Steph Ulmer

BAMBINI trial: Bariatric surgery superior to medical care for treating PCOS

May 29, 2024 3 min read

Bariatric surgery is superior to medical care for treating women with polycystic ovary syndrome (PCOS), oligomenorrhoea or amenorrhoea and obesity, according to the findings from the Bariatric Surgery vs Medical Care For Obesity And Polycystic Ovarian Syndrome Related Infertility (BAMBINI) randomised controlled trial, published in the Lancet. Patients who underwent surgery also experienced a greater increase in spontaneous ovulation rate, cardiometabolic risk factors, psychological health and quality of life at 52 weeks of follow-up, compared with those who received medical care.

Alexander Miras

“To our knowledge, BAMBINI is the first RCT to compare the effect of bariatric surgery with medical care in women living with PCOS, obesity, and oligomenorrhoea or amenorrhoea. The trial showed that women after vertical sleeve gastrectomy had a significantly higher rate of spontaneous ovulatory events, approximately 2.5 times greater than that of the medical group over the 52-week follow-up period,” explained Dr Alexander D Miras from Imperial College London, London and Ulster University, Derry, UK, co-author of the paper. “Ovulation was confirmed biochemically using weekly serum progesterone measurements. Participants in the surgical group had significantly greater improvements in anthropometrics, cardiometabolic risk factors, biochemical hyperandrogenism, quality of life, and psychological health compared with the medical group. There were no significant differences between the groups in clinical hyperandrogenism.”

PCOS is the most common cause of anovulatory infertility and obesity is known to  exacerbates the reproductive complications of PCOS. However, bariatric prior to BAMBINI, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. Therefore, researchers from the UK designed a RCT to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity and oligomenorrhoea or amenorrhoea.

The study recruited 80 women with a diagnosis of PCOS (based on the 2018 international evidence-based guidelines for assessing and managing PCOS) and a BMI of 35 kg/m2 or higher. Participants were randomly on a 1:1 ratio to the medical or surgical group and underwent assessments by a physician, dietitian, psychologist, and surgeon.

Lifestyle modification was performed by specialist dietitians at online group sessions and one-to-one consultations every two weeks for the first 26 weeks of the trial and subsequently once every four weeks for the remaining 26 weeks.  In the surgical group, participants were postoperatively assessed by a clinical nurse specialist at ten days, six months and 12 months, and by a dietitian at three months. The primary endpoint was the number of biochemically confirmed spontaneous ovulatory events (measured by weekly serum progesterone) expressed as an incidence ratio over 52 weeks.

A total of four participants in the surgical group did not receive the intervention and three participants in the medical group were lost to follow-up, and two dropped out due to work commitments. In the surgical group, five participants were lost to follow-up. Therefore, 63 (79%) of the participants completed the trial.

Outcomes

In the intention-to-treat analysis, the incidence rate for the primary endpoint was 4.1 events per year in the surgical group and 1.9 events per year in the medical care group (p<0.0007). Similar results were obtained from the per-protocol analysis (p<0·0010). The difference in the incidence of ovulatory events between the groups was evident by 8 weeks after the intervention and increased further over 52 weeks.

Participants in the surgical group experienced a significant reduction in weight (125.2kg at baseline and 89.5 kg at 52 weeks), but not the medical group (116.3kg at baseline and 118.7kg at 52 weeks). Moreover, there was a significant reduction in waist circumference and a decrease in glycated haemoglobin in the surgical group, as well as significant differences in systolic blood pressure, diastolic blood pressure, fasting glucose, fasting insulin, and triglyceride concentrations between the medical and surgical groups at 52 weeks. There was a significant reduction in HOMA-IR in the surgical group, but not in the medical group, with a significant difference between the groups at 52 weeks.

“Due to the absence of RCT evidence, the diagnosis of PCOS and obesity has yet to feature explicitly in national or international guidelines as an indication for bariatric surgery.49 The results of this trial could inform guidelines and medical insurance providers to offer bariatric surgery to increase the prospects of fertility for women with obesity, PCOS, and oligomenorrhoea or amenorrhoea,” the authors concluded. “In fact, the second International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome now recommends bariatric surgery as a treatment option to improve cardiometabolic risk factors, ovulation, and pregnancy rates in women with PCOS and obesity.”

The findings were featured in the paper, ‘Bariatric surgery for spontaneous ovulation in women living with polycystic ovary syndrome: the BAMBINI multicentre, open-label, randomised controlled trial’, published in The Lancet. To access this paper, please click here

Non-surgical weight loss in a capsule - watch this space!

16 May 2023

Hi All,

I love seeing articles like this that describe what may be coming over the horizon for obesity management.  Anti-Obesity Medications (AOMs) have been becoming more mainstream which is likely to make them more accessible and affordable.  This is an interesting one though, because it isn't actually a medication - it acts locally on the GI tract.  The obvious advantage of this is that there are fewer side effects.  It's main mechanism of action is to absorb gut contents which then decreases the absorption of calories and sugar from a meal.  The weight loss stats appear to be impressive too. 

We are using more AOMs in the treatment of obesity in the pre-op stage and even as an adjunct in the post-op stage.  Saxenda is being used by some - it is expensive and has a significant side effect profile that makes it intolerable to some.  Ozempic, Saxenda's cousin, has recently been approved by Medsafe for use in New Zealand - so look out for that becoming available too.  Exciting times!  With any of these medications, it is a case of trying it for yourself for 6 weeks and seeing how it works for you.  Please contact us if you need more information or advice regarding AOMs.  We look forward to making contact.

Happy days,

Steph

Results from the LIGHT-UP clinical trial for adults with overweight or obesity who have prediabetes or type 2 diabetes and were treated with either GS200 or placebo, revealed that approximately six out of ten adults treated with GS200 achieved clinically meaningful response to treatment (achieving at least 5% body weight loss), losing on average 11% of their body weight (~23lbs) and an average reduction of 5.5 inches off their waist circumference. The findings were presented at the European Congress on Obesity 2022.

GS200 is a non-systemic, superabsorbent hydrogel in development for the treatment of obesity and for glycemic control. It is made by utilizing the same proprietary hydrogel platform technology Gelesis developed for its previously FDA cleared product, GS100 (Plenity). Like GS100, GS200 is made from naturally derived cross-linked modified cellulose, however with a higher molecular weight.

GS200 was designed to hydrate faster and create a higher elastic response in the GI tract compared with GS100. Its properties were optimised in preclinical studies based on its effect on the gut barrier and microbiome, as well as reduced insulin resistance and weight loss. Like GS100, GS200 is a three-dimensional matrix of cellulose, capable of absorbing a much larger volume of water in the stomach and small intestines.

 Orally administered in capsules with water before meals, GS200 particles rapidly absorb water in the stomach and homogenously mix with ingested food. This creates thousands of small individual gel pieces with composition (cellulose and water) and elasticity (firmness) similar to solid ingested raw vegetables, without any caloric value. Once it arrives in the large intestine, the hydrogel is partially broken down by naturally occurring enzymes, and loses its three-dimensional structure along with most of its absorption capacity.

 The released water is reabsorbed in the large intestine, and the remaining cellulosic material is expelled naturally. GS200 is considered a medical device because it achieves its primary intended purpose through mechanical modes of action consistent with mechanobiology constructs, and it is not absorbed through the gastrointestinal tract. GS200 received a Non-Significant Risk (NSR) determination by the FDA for the LIGHT-UP study.

 Participants in LIGHT-UP were also instructed to follow a modestly reduced calorie diet along with moderate-intensity physical activity. In the GS200 group there was clear and early separation between responders and non-responders to treatment, and response to therapy could be predicted as early as 6 weeks of treatment.

“There is a very large population of adults with prediabetes and diabetes who have a greater need for weight loss due to higher medical risks and a greater difficulty losing weight,” said Dr Frank L Greenway, Medical Director and Professor at the Pennington Biomedical Research Center of the Louisiana State University and one of the study’s lead investigators. “The compelling weight loss data that favours diabetes and prediabetes is unique among weight loss treatments. Its convenient oral administration, and very favourable tolerability make it a potentially important tool to aid clinicians and patients achieve clinically meaningful weight loss.”

The multicentre, double-blind, randomized, placebo-controlled study enrolled 254 subjects and was designed to assess the change in body weight in adults with overweight or obesity, who have prediabetes or diabetes, after six months of treatment with a new oral superabsorbent hydrogel (GS200) or placebo. The study met both of its primary endpoints: the proportion of participants who achieved at least 5% body weight loss and the change in body weight after six months of therapy.

A highly binary effect was observed with the GS200 treatment group, with a clear separation between responders and non-responders as early as after 6 weeks of treatment. Among the adults who completed the study protocol requirements (PP population), 64% of GS200-treated adults were Responders vs. 41% in the placebo group (p=0.001). In the analysis which also included data from the participants who didn’t fully complete the study (ITT-MI), 55% of GS200-treated adults were Responders vs. 34% in the placebo group (p=0.0004). The average body weight loss of the Responders was 11% (approximately 23 pounds) and their waist circumference was reduced by 5.5 inches on average.

 Importantly, Gelesis treated individuals had 2.8 higher odds compared with placebo to become Responders (p=0.0004), achieving the first primary endpoint of the study.

With respect to average total weight loss, the complete GS200 treatment group (including both Responders and Non-Responders) demonstrated superiority over placebo after 6 months of treatment (body weight loss of 7.1% vs. 4.6%, P=0.0029 in the PP population or 6.9% vs. 4.3%, P=0.0011 in the ITT population), thereby achieving the second primary endpoint.

 GS200 demonstrated a highly favorable safety and tolerability profile as the overall incidence of adverse events (AEs) in adults treated with GSP200 was similar to the incidence of AEs in the placebo group.

 Approximately 1 out of 3 GS200-treated adults were “super responders,” losing at least 10% of their body weight and on average losing 13% (~30lbs) or 7 inches off their waist circumference.

“There is a real need for tolerable, effective, and affordable therapeutics to aid in weight loss for patients with prediabetes and type 2 diabetes. Approximately 130 million Americans have prediabetes or type 2 diabetes and approximately 80% struggle with excess weight. Importantly, these individuals also have a high risk of heart disease and other serious chronic conditions, related to overweight and obesity, making this one of the biggest public health issues facing our society,” said Harry L. Leider, MD, MBA, FACPE, Chief Medical Officer of Gelesis. “These data show that GS200 produces clinically meaningful weight loss for the majority of patients and that it’s possible to identify these responders early in treatment. Given the highly attractive safety and tolerability profile, GS200 has the potential to become an exciting new therapy, especially among those in the lower spectrum of excess weight who also have prediabetes or type 2 diabetes.”

Brain networks can play a role in weight loss success.

7 April 2023

Hello all,

Whilst we know that our body weight and BMI is determined by many factors, it is the role of the brain that is very difficult to measure and see.  This study uses functional scans of the brain to measure activity in different parts of the brain.  The scans are repeated after food based stimuli are given to see how they affect the brain activity.  The change in the functional activities of the brain are compared with weight loss outcomes after a "behaviour-based intervention" was given.  The weight loss outcomes were directly correlated with the degree of activity in these specific brain networks, seeming to suggest that brain activity is dictating how well a patient is able to lose weight with a treatment.  Whilst it doesn't give us any solution in the pursuit of optimising weight loss outcomes, it does open up avenues for further research and targeted therapy trials that may ultimately give results. Each contribution to research in this area helps with getting closer to answers that may result in more effective treatments for obesity - and we can all be happy with that.

Happy Easter and kind regards,

Steph  

Wake Forest University School of Medicine researchers discovered that two specific brain networks can greatly impact how successful a person is at losing weight. According to the study’s principal investigator, Dr Jonathan Burdette, professor of radiology at Wake Forest University School of Medicine, these findings may eventually aid in the development of tailored behavior-based treatments that target specific brain circuitry to aid in weight loss. The outcomes featured in the paper, ‘Longitudinal relationship of baseline functional brain networks with intentional weight loss in older adults’, published in Obesity.

“These findings show that the brain network properties of people who were less successful at weight loss were different from folks who were more successful,” explained Burdette. “Some people have a stronger unconscious sensory motor bias to pursue food, while others appear to have less. In a society of food abundance with food cues everywhere, this information can help explain why some people have such difficulty in taking off excess weight and maintaining it.”

The goal of the Empowered with Movement to Prevent Obesity and Weight Regain (EMPOWER) study was to determine whether the degree of weight loss after six months of a behaviour-based intervention was related to connectivity within two functional networks (FNs), FN1 and FN2, in a group of older adults with obesity. Functional brain networks are areas of the brain that are working together in sync. FN1 and FN2 were first identified by Burdette and his team in 2018 as being involved in successful weight loss.

In total, 71 participants enrolled in a randomised weight-loss clinical trial were scanned at the beginning of the trial with functional magnetic resonance imaging to determine if FN1 and FN2 would be predictive of weight loss and if so how. Participants were scanned during a resting state and then again after receiving a food-cue task. At the end of the six-month trial, the data were then analysed to compare the relationships between the baseline networks and the change in the participants’ weight.

Burdette’s team found that during the resting state the relationship of brain function in FN1, which involves sensory and motor skills, was significantly associated with six-month weight loss. During the food-cue state, six-month weight loss was significantly associated with FN2, which includes self-regulation and the ability to focus attention.

Two distinct brain network biases are related to the degree of success with weight loss: within the resting state, there is a sensory motor motivational bias to pursue food, whereas when processing food cues, there is a deficit in the executive control and attention network.

This is the first study to link key concepts that have been identified as important in understanding obesity and overeating to success with behavioural weight loss among older adults with obesity.

“Our findings provide further insight into complex functional circuits in the brain so we now have a mechanistic understanding of why people aren’t losing weight,” he added. “In theory, if you know more about urges and control, we will be able to tailor therapies to an individual as opposed to treating everyone the same.”