GLP-1 agonists to be among 15 drugs subject to Medicare price negotiations
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As you can imagine this space has attracted a lot of attention. I get email summaries of top stories of drug development from StatNews and Endpoints News every day. Though I’m not seeking it, I can’t help but absorb information about clinical trials of next-gen products. Lily and Pfizer lead the way. Novo Nordisk is doing research too.
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Me: What’s the next generation of weight loss drugs after GLP-1 agonists.
ChstGPT:
The landscape of weight loss medications is rapidly evolving beyond traditional GLP-1 receptor agonists, with several promising developments on the horizon:
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Multi-Receptor Agonists:
• Dual and Triple Agonists: Pharmaceutical companies are developing drugs that target multiple receptors to enhance weight loss efficacy. For instance, Eli Lilly’s retatrutide is a “triple G” agonist that activates GLP-1, GIP, and glucagon receptors. In mid-stage trials, participants achieved up to 24.2% weight loss over 48 weeks, marking significant progress in obesity treatment.  -
Amylin Analogues:
• Amylin-Based Therapies: Drugs like cagrilintide and petrelintide mimic the hormone amylin, which promotes a feeling of fullness after eating. These therapies offer an alternative mechanism to existing GLP-1-based treatments and have shown promise in early trials.  -
Oral GLP-1 Receptor Agonists:
• Convenient Pill Forms: Efforts are underway to develop effective oral GLP-1 receptor agonists. Eli Lilly’s orforglipron and Pfizer’s danuglipron are notable examples, aiming to provide the benefits of GLP-1 therapies without the need for injections.  -
Novel Targets and Mechanisms:
• NK2R Agonists: Researchers at the University of Copenhagen, funded by Novo Nordisk, have identified the neurokinin 2 receptor (NK2R) as a potential target for weight loss drugs. Early studies suggest that NK2R agonists can decrease appetite and increase calorie burning without causing nausea, a common side effect of current treatments. Clinical trials are anticipated to begin within a year, with potential public availability in five to six years. 
These advancements reflect a concerted effort to develop more effective, convenient, and tolerable weight loss medications, addressing the diverse needs of individuals seeking obesity treatment.
Only non-witches get due process.
- Cotton Mather, Salem Massachusetts, 1692
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Me: What’s the next generation of weight loss drugs after GLP-1 agonists.
ChstGPT:
The landscape of weight loss medications is rapidly evolving beyond traditional GLP-1 receptor agonists, with several promising developments on the horizon:
-
Multi-Receptor Agonists:
• Dual and Triple Agonists: Pharmaceutical companies are developing drugs that target multiple receptors to enhance weight loss efficacy. For instance, Eli Lilly’s retatrutide is a “triple G” agonist that activates GLP-1, GIP, and glucagon receptors. In mid-stage trials, participants achieved up to 24.2% weight loss over 48 weeks, marking significant progress in obesity treatment.  -
Amylin Analogues:
• Amylin-Based Therapies: Drugs like cagrilintide and petrelintide mimic the hormone amylin, which promotes a feeling of fullness after eating. These therapies offer an alternative mechanism to existing GLP-1-based treatments and have shown promise in early trials.  -
Oral GLP-1 Receptor Agonists:
• Convenient Pill Forms: Efforts are underway to develop effective oral GLP-1 receptor agonists. Eli Lilly’s orforglipron and Pfizer’s danuglipron are notable examples, aiming to provide the benefits of GLP-1 therapies without the need for injections.  -
Novel Targets and Mechanisms:
• NK2R Agonists: Researchers at the University of Copenhagen, funded by Novo Nordisk, have identified the neurokinin 2 receptor (NK2R) as a potential target for weight loss drugs. Early studies suggest that NK2R agonists can decrease appetite and increase calorie burning without causing nausea, a common side effect of current treatments. Clinical trials are anticipated to begin within a year, with potential public availability in five to six years. 
These advancements reflect a concerted effort to develop more effective, convenient, and tolerable weight loss medications, addressing the diverse needs of individuals seeking obesity treatment.
@jon-nyc said in GLP-1 agonists to be among 15 drugs subject to Medicare price negotiations:
more effective, convenient, and tolerable
The important word is "tolerable."
Somewhere, I saw a report that about 50% of people taking GLP-1 agonists stop after 1 year because of side effects.
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Also, the relationship between ghrelin and leptin polypeptides (hunger and satiety) is a field of study. I would think that amylin analogues (as you ChatGPT comment) might be an easier lift for treatment of obesity. Also, perhaps, more physiologic than making you puke, slow your stomach's emptying and have diarrhea.
Nevertheless, you have to wonder what's driving the obesity epidemic.
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@jon-nyc said in GLP-1 agonists to be among 15 drugs subject to Medicare price negotiations:
I think we all know. It’s the SAD*. And insufficient exercise.
People were
normalskinny in the 1960s. Was the diet substantially different? They ate butter, eggs, etc. IOW all the things we were told were bad for you.I'm too lazy to look up the caloric intake of the average American back then compared to now.
As an aside, remember the comment that "The United States is one of the few (if not only) countries in which people living in poverty are obese."
"Now look here, you Baltic gas passer... " - Mik, 6/14/08
The saying, "Lite is just one damn thing after another," is a gross understatement. The damn things overlap.
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@jon-nyc said in GLP-1 agonists to be among 15 drugs subject to Medicare price negotiations:
I think we all know. It’s the SAD*. And insufficient exercise.
People were
normalskinny in the 1960s. Was the diet substantially different? They ate butter, eggs, etc. IOW all the things we were told were bad for you.I'm too lazy to look up the caloric intake of the average American back then compared to now.
As an aside, remember the comment that "The United States is one of the few (if not only) countries in which people living in poverty are obese."
@George-K said in GLP-1 agonists to be among 15 drugs subject to Medicare price negotiations:
@jon-nyc said in GLP-1 agonists to be among 15 drugs subject to Medicare price negotiations:
I think we all know. It’s the SAD*. And insufficient exercise.
People were
normalskinny in the 1960s. Was the diet substantially different? They ate butter, eggs, etc. IOW all the things we were told were bad for you.I'm too lazy to look up the caloric intake of the average American back then compared to now.
As an aside, remember the comment that "The United States is one of the few (if not only) countries in which people living in poverty are obese."
ETA: In the mid 1970s, in medical school, we used to talk about the "average 70 kg. man".
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@jon-nyc said in GLP-1 agonists to be among 15 drugs subject to Medicare price negotiations:
I think we all know. It’s the SAD*. And insufficient exercise.
People were
normalskinny in the 1960s. Was the diet substantially different? They ate butter, eggs, etc. IOW all the things we were told were bad for you.I'm too lazy to look up the caloric intake of the average American back then compared to now.
As an aside, remember the comment that "The United States is one of the few (if not only) countries in which people living in poverty are obese."
@George-K said in GLP-1 agonists to be among 15 drugs subject to Medicare price negotiations:
@jon-nyc said in GLP-1 agonists to be among 15 drugs subject to Medicare price negotiations:
I think we all know. It’s the SAD*. And insufficient exercise.
People were
normalskinny in the 1960s. Was the diet substantially different? They ate butter, eggs, etc. IOW all the things we were told were bad for you.There wasn’t nearly as much highly processed food and refined sugars in our diet in the 60s.
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How different is the SAD than the American diet in the 1960s
The Standard American Diet (SAD) today is significantly different from the American diet of the 1960s due to changes in food production, processing, and consumption habits. Here’s a breakdown of the key differences:
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Processed Foods
• 1960s: Processed foods existed but were less prevalent. Many meals were prepared at home using fresh or minimally processed ingredients. Canned and frozen foods were common but not as heavily processed as today.
• Today: The SAD is dominated by ultra-processed foods (e.g., packaged snacks, ready-to-eat meals, fast food) that are high in added sugars, unhealthy fats, and sodium. -
Added Sugars and Sweeteners
• 1960s: Sugar consumption was primarily from sucrose (table sugar) in home-cooked meals, baked goods, and sodas. High-fructose corn syrup (HFCS) was not yet widely used.
• Today: HFCS and other added sugars are ubiquitous, especially in beverages, snacks, and sauces. Americans consume significantly more sugar now than in the 1960s, largely due to the proliferation of sugary drinks and processed snacks. -
Fats and Oils
• 1960s: The diet included more natural fats like butter, lard, and animal fats. Margarine and vegetable oils (e.g., corn oil, soybean oil) were becoming more popular.
• Today: The SAD is high in industrial seed oils (like soybean and canola oil) and trans fats (though these are now being phased out). These fats are found in fried foods, baked goods, and processed snacks. -
Portion Sizes
• 1960s: Portions were smaller. For example, a standard Coca-Cola bottle was 6.5 ounces, compared to today’s 20-ounce bottles or even larger sizes.
• Today: Portion sizes have dramatically increased, contributing to higher calorie consumption and rising obesity rates. -
Eating Habits
• 1960s: People ate more meals at home, often as a family. Dining out was less frequent and considered a special occasion.
• Today: Americans eat out or order takeout frequently, consuming more fast food and highly processed meals. -
Meat Consumption
• 1960s: Meat was a significant part of the diet, but portions were smaller, and meat was often cooked at home.
• Today: Americans consume more processed meats (like hot dogs, sausages, and deli meats) and large portions of meat, often through fast food. -
Whole Grains vs. Refined Grains
• 1960s: Breads and grains were less refined, though white bread was a staple.
• Today: The SAD is heavily reliant on refined grains (white bread, pasta, pastries) with fewer whole grains. -
Fresh Produce
• 1960s: Fruits and vegetables were more commonly included in meals, and local or seasonal produce was more common.
• Today: Despite greater year-round availability, Americans consume less fresh produce and more processed forms (e.g., fruit snacks, canned soups). -
Caloric Intake
• 1960s: Average daily caloric intake was around 2,000–2,200 calories.
• Today: Caloric intake has increased significantly, with the average around 2,500–2,700 calories due to larger portions and more calorie-dense, processed foods. -
Obesity and Health
• 1960s: Obesity rates were significantly lower (around 13% of adults were obese).
• Today: Obesity rates have skyrocketed to around 42% of adults, largely driven by changes in diet and lifestyle.
Conclusion:
The American diet has shifted dramatically from home-cooked, whole-food-based meals in the 1960s to a diet dominated by ultra-processed foods, added sugars, refined grains, and larger portions. This transition has had profound impacts on public health, contributing to the rise in obesity, diabetes, and other diet-related illnesses.
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@jon-nycChatGPT, that's a good summary.No question, in my mind, that larger portions and overall increased caloric intake are major driving forces. People have been talking about HFCS as being a problem for a long time. Is there any science that processed foods and HFCS are drivers of obesity by themselves? Or are they part of the portion and calorie stuff.
I remember reading how much sugar is in something we thought of as "healthy" - Cheerios, I believe. The amount of sugar and salt in it was amazing.
I saw a story that one fast food chain - In-And-Out? - was switching to beef tallow for their french fries.
"Now look here, you Baltic gas passer... " - Mik, 6/14/08
The saying, "Lite is just one damn thing after another," is a gross understatement. The damn things overlap.
