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Welcome to the Obesity Pulse Translating Obesity Science. My name is Doctor Patrice Forner. I am an endocrinologist and this is the EASD Micro Masterclass. So today we're going to run through the updates from the European Association for the Study of Diabetes, evaluating new clinical data to individualize obesity care. And we'll start with a case, so this is Maya, she's a 52 year old female, she has a BMI of 35, she has prediabetes with a HbA1C of 6.2% and hypertension. She's previously lost weight with lifestyle intervention, but unfortunately she's regained and she has persistent hunger and food cravings. She wants to lose weight and she wants to maintain strength and physical function, and she says there are so many new weight loss treatments being discussed in the news. What does the latest evidence mean for someone like me? So let's take a look at some of the evidence presented at EASD. So we'll start with Cadry-Sema, so this is a combination of cagrelintide and simaglatide. So this study evaluated the effects of Cadry-Sema on appetite, eating behavior, food intake, and brain responses to food cues in adults with overweight and obesity using functional MRI. So they had a total of 130 adults without type 2 diabetes and with low craving control, and they were randomized to once weekly Cadryema 2.4 2.4 mg or placebo. Now the end points included patient reported appetite, energy intake, eating behavior questionnaires, body weight, and functional MRI responses to to food cues. So the results showed that Cadryema significantly reduced patient reported appetite versus placebo at weeks 22 and 52, and that's shown in the figure on the left, and total energy intake, that's the image on the right, was also substantially reduced versus placebo. So overall these findings show sustained effects on appetite and food intake over 52 weeks. Now Cadbury Summer also produced sustained improvements across several measures of eating behavior, including a reduced preference for high fat, high sweet food. There was improvement on several self-reported measures of cravings, hunger, craving control, and responsiveness to food cues at weeks 22, and that's shown in the green, and weeks 52 shown in the blue. The functional MRI results depicted on the right show changes in brain regions involved in appetite regulation, reward processing, food anticipation, and executive control, and different patterns of neural response were observed at week 22 and 52, again shown in green and blue respectively. So together these results provide additional insight into how Cadbury semin may affect the biological and behavioral drivers of eating beyond weight reduction alone. Now let's move on to retatritide, this is Triumph 2, so Triumph 2 evaluated retatritide. Now retatritide is a GIP GLP-1 and glucagon receptor agonist, and this is in adults with overweight or obesity with type 2 diabetes. This is a randomized multinational phase 3 trial that enrolled 1,152 participants and compared once weekly retatritide at a dose of 49 or 12 mg with placebo over 80 weeks. You can see the mean body weight reductions in the image on the bottom left of your screen, so weight reduction was 12.7% with retached retide 4 mg, 19.1% with 9 mg, and 20.8% with 12 mg compared with only 4% with placebo. If you look at the top right, at least 20% weight loss was achieved by 24%, 45.3%, and 52% of participants receiving 49 and 12 mg respectively versus 1.5% with placebo. So at least 25% weight loss was achieved by 10.8, 30.6%, and 34.9% respectively versus 0.8 with placebo. If you look at the bottom right of your screen, you're going to see an indirect comparison with the other phase 3 studies. This shows the percent weight change for simaglatide, so it's our GLP-1 receptor agonist, versus tazepatide, our dual agonist, and retatratide, the triple agonist, and we know that we shouldn't draw conclusions across separate trials, but retatratide results in the highest percent weight loss we've seen to date in a population with type 2 diabetes. This is synchronized to, synchronized to evaluated savodatide, savodatide's a glucagon and GLP-1 receptor dual agonist, and they evaluated it in adults who are overweight or obesity and type 2 diabetes. At a total of 755 participants, they were randomized to savodatide 3.6 6 mg or placebo through week 76. Looking at the image at the bottom left of your screen, the mean body weight reductions were 10.4 with savoda tide 3.6 mg and 13.1% with 6 mg compared with 3.1% with placebo. At least 5% weight loss was achieved by 58% and 65% of participants receiving 3.6 and 6 mg respectively, versus 35% with placebo. Mean HbA1c reductions were 0.9 and 0.8% points with savoda tide, that's compared to 0.2% with placebo, and waist circumference and systolic BP also decreased. The most common adverse events were gastrointestinal and generally mild to moderate and transient. This is a phase two study evaluating aora lintide, a selective amylin receptor agonist alone and in combination with tezepetide in 367 adults with overweight or obesity and type 2 diabetes. At week 48, body weight reduction was 3% with placebo and ranged from 8.2 to 12.3% across the aoraintide alone regimens shown in blue. Tezepetide 15 mg produced a 14.8% reduction in body weight, that's in black on the far right of your screen. Allorolintide and tezepetide produced reductions ranging from 13.2% to 23.3%, with the greatest reductions seen with alorolintide 36 and 9 mg plus tezepetide 15 mg. Adding a laurelintide to established tezepetide treatment was associated with a 20.6% reduction in body weight. So the combination produced significantly greater body weight reductions than either therapy alone. There's been a lot of talk about maintenance of muscle mass with all of these weight loss therapies. This is Courage, Courage evaluated travogramab, which is an anti-myostatin antibody added to simaglatide in adults with obesity without diabetes. So this was a randomized double-blind placebo-controlled phase two study assessing changes in lean body mass, fat mass and body weight. Across the tovogramab doses, so it's 25, 75, 200, and 400 mg, lean mass loss was lower than with simaglatide plus placebo. The 240 mg tovogramab dose was associated with significantly greater fat mass loss than than simaglatide plus placebo at week 26. So overall, the study showed preservation of lean mass during simaglatide associated weight loss, with additional fat loss observed at the highest travogumab dose. This is the MRI analysis from the COURAGE study, so looking at muscle fat infiltration on the left, fat tissue free muscle volume in the middle, and muscle volume Z score on the right. At week 52, muscle fat infiltration decreased by 0.24% points with symaglotite alone, so that's the green line. Compared with reductions of 0.6 in the pink line and 0.76% points the purple line with travogramab 25 mg and 75 mg. Fat tissue free muscle volume declined by 1 L or 8.7% with simaglatide alone, compared with approximately 03 0.3 L or 2.6 to 2.9% with travogramab. Muscle volume Z score declined by 0.40 with simaglatide alone but increased by 0.2 and 0.21 with travolumab 25 and 75 mg. So the study showed greater preservation of lean mass alongside improvements in the MRI measures of muscle quantity and quality. So this brings us to our first question. How would you interpret the new EASD evidence for Mayer in your discussion today? The latest study data, A, suggests that weight loss should remain the main measure of how well treatment is working. B, suggest future treatments may help with weight, blood sugar, hunger, and muscle health. C, show that controlling hunger is the key to successful obesity treatment. Or D, show that protecting muscle should be the main goal during weight loss. And the answer is B. So the new ESD data highlights that emerging obesity therapies can affect multiple outcomes relevant to MA, uh, and this includes body weight, glycemia.