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Hello, everyone, and thank you so much for joining us today for the Global Obesity Academy International Program. My name is Doctor Sue Peterson. I'm an endocrinologist and obesity medicine specialist in Calgary, Canada, and I'm delighted to take you through this presentation that I've developed for you today. These are my disclosures. OK, let's now move into our second objective, which is to discuss how to reassess and adjust therapy when targets of treatment are not being met. So, polling question here again for you. What are the most appropriate targets of obesity treatment? Is it health benefits? Is it percentage weight loss? Is it treatment targets that the patient decides, Quality of life improvement, or is it as determined in partnership with the patient and the healthcare professional? I'll give you a few seconds. Wonderful. Thank you so much for your responses. So the best answer to this question here was E, as determined in partnership between the patient and the healthcare professional. So let's talk about that in the context of Sabine. So Sabine is 62. She's retired. She has a past history of severe obstructive sleep apnea, doesn't tolerate CPAP. She has knee osteoarthritis, controlled hypertension, hypothyroidism, and obesity. And here we see her medication list for these conditions, and that includes imaglotide 2.4 mg weekly, which she's taking for weight management. If we look at her lab and assessment, we see that her BMI is 34. Her waist to height ratio is elevated at 0.64. Her waist circumference also is elevated at 100 centimeters. She has a good A1C, BP controlled. She is well replaced on her thyroid hormone with a normal range TSH. Little bit of elevation in triglycerides, very common, and she's, uh, got a little bit of chronic kidney disease actually based on today's lab with a GFR of 55. So, in terms of her history, she started Semaglutide about 9 months ago, uh, tolerated it well, uh, titrated her way up. Her targets of treatment that were identified in partnership with our healthcare professional and Sabine were improvement in her knee pain. She wants her knees to hurt less. We'd like her sleep apnea to improve, and Sabine says, I'd like to lose at least 15% of weight. That is an important treatment goal for me. So, we incorporate that into the treatment paradigm. So, her response to Semelatide over 9 months has been a little improvement in knee pain. Her sleep apnea has improved a little bit as well. It's now in the high moderate range, and she's lost about 5% weight, and her weight has plateaued. So, what if my patient's not responding to treatment? So, here we have a case of Sabine where we're not meeting the goals of treatment. We've had some benefit, but we haven't really substantially improved her sleep apnea. We can likely do more. Um, we have not met her weight loss goals which were very important to her as a target of treatment, and she'd like some improvement. in her knee pain as well. So, the first thing is not to assume that we're not getting benefits in health with the weight loss because health improvements can be realized with less weight loss. But here, we're seeing that we have not had the weight loss that she would like and we have not met the treatment goals for her obesity-related health issues. So, if goals of treatment aren't being met, that doesn't necessarily mean that the medication isn't working. There's other things we need to think about first. Does our patient have continued access to treatment? If they're paying out of pocket, can they still afford it? Is the dose adequate for the desired to Effect? Are there adherence challenges or tolerance challenges? Is she encountering barriers to health behavior change? Are there other psychosocial issues or medical issues or medications maybe that have been started that have been causing weight gain? So we need to go through all of these things with her. After assessing these factors, if we feel that the goals of treatment are not being met on the maximum tolerated dose, we can revisit the pillars of obesity treatment, those being psychological support, pharmacotherapy, and bariatric surgery, and we can consider adding or substituting another medication or intervention to the patient's treatment. So as Sabine hasn't met health targets nor her weight loss goals, are there alternatives to her current treatment? Well, surmount 5 was a direct head to head comparison of semeglutide versus rezepetide for weight management. They found that the average weight reduction was 20.2% with rezepetide at the maximum tolerated dose of 10. 15 mg weekly versus 13.7% with semelutide at the maximum tolerated dose of 1.7 or 2.4 mg weekly. And Sabine wants to lose 15% weight. On the right, we see that 65% of people achieve this with repetide versus 40% of people with semmelutide. Now, for obstructive sleep apnea, which Sabine has, there's robust evidence for trazepetide in particular to improve sleep apnea in people on and not on positive airway pressure therapy. The reglutide can actually also provide a modest improvement in sleep apnea along with a modest weight loss. Sabine's not On CPAP, so she'd be similar to the patients here on the left in the terpeide study, where there was a marked reduction of 25 events per hour versus 5 with placebo and accompanied by an average of nearly 18% weight loss. So this would fit, fit really well with Sabine's treatment goals. Sabine also has osteoarthritis, where the only obesity medication showing benefit is semaglutide, with a significant greater reduction in the Womack pain scale with semaglutide versus placebo, and with a 13.7% mean weight reduction with semaglutide. But she's already on semaglutide. She's on maximum dose, she's tried it, she's adherent, and it hasn't worked for her, so we should move on to something else. So it's really hard to think through all these trials in a busy clinic day, but with our Obesity Canada clinical Practice guideline decision tool, we can really quickly look at the rows here on obstructive sleep apnea and on osteoarthritis, and the weight loss at the bottom because that's one of Sabine's treatment goals, and we see that terzepetide becomes the best choice. She hasn't succeeded with immelutide, so we'll see if terzepetide provides a better success. So, we suggest switching immelutide to terzepetide, and Sabine would really like to do that. Now, as to what dose to switch to, well, that depends on current tolerance of simaglatide and what dose of simmaglatide the patient's currently taking. There aren't any specific data currently to guide us on this, only clinical experience. As she's tolerating semaglutide well, I would suggest switching to tezepetide 5 mg, or you could even switch to 7.5 mg weekly and titrate. But typically, I would err on the more conservative side. I'd probably switch Sabine to 5 mg weekly. Now, remember, there's some important things we have to watch here as we are switching to terpetide and then potentially titratingterzeetide. She has hypertension. And remember that hypertension medication needs may decrease even before substantial weight loss with highly effective GLP-paced therapies. So we need to have her watching her BP at home and be careful to adjust BP medication. If she's having a reduction in BP, she might not need as much BP medication with the switch to repetite. Now, thyroid hormone needs can also decrease with weight loss, and that's really important. Again, we don't have any data to guide us on a specific evidence-based approach here, but what I typically do is check thyroid hormone levels every 2 months for the 1st 6 months or sometimes even monthly if the patient has health conditions where they may be more sensitive to changes in thyroid hormone like coronary artery. Disease. And I always recheck 1 month after any dose change in thyroid hormone. At 6 months, we can evaluate what's the current trajectory of weight loss. If it is slowed, then we might be able to move the thyroid hormone level checks to less frequently, like every 3 months. But remember, this is very individualized and it's important to make these monitoring decisions individually based on the patient.