Advancements in Diabetes and Obesity Treatments

Single-receptor glucagon-like peptide-1 (GLP-1) agonists were originally developed as treatments for type 2 diabetes and have recently surged in global popularity due to their ability to improve metabolic health and pharmacologically treat obesity. A new review led by Christine M Kusminski at The University of Texas Southwestern Medical School details the development of multi-receptor agonists developed for obesity therapy that target combinations of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors. Transforming obesity: The advancement of multi-receptor drugs. https://lnkd.in/exm_k737 The authors described the rationale for combining GLP-1 and glucagon receptor activation, detailing the development of several key GLP-1R/GCGR co-agonists. They then extensively discussed GLP-1R/GIPR co-agonists, with a primary focus on tirzepatide. They present comprehensive clinical data from the SURPASS and SURMOUNT trial programs, showcasing tirzepatide's superior efficacy in both glycemic control and weight loss. The review also includes  in a discussion of triagonist peptides targeting GLP-1, GIP, and glucagon receptors simultaneously. The authors presented both preclinical and early clinical data on these compounds, with a particular focus on retatrutide. They highlighted the unprecedented weight loss achieved with these agents, noting that they approach the efficacy of bariatric surgery. The authors also addressed potential limitations and side effects of these therapies. They discussed the phenomenon of weight regain upon treatment discontinuation, concerns about loss of lean mass, and the challenges of using these therapies in specific populations. The review also touched on the current supply limitations and high costs of these novel therapies. In their conclusion, the authors reflected on the remarkable progress made in obesity pharmacotherapy. They positioned these advancements as a potential turning point in obesity treatment, while also emphasizing the need for long-term safety data and equitable access to these transformative therapies. The authors highlighted ongoing challenges and areas for future research, including the need to better understand the precise mechanisms of action for each receptor component in multi-agonist therapies.

Eli Lilly has made a $2 billion bet on a drug that helps people lose fat and gain muscle at the same time. The drug is called bimagrumab. It was originally developed for rare muscle-wasting diseases, but in a trial involving people with obesity and type 2 diabetes, researchers noticed something unexpected. Participants who received the drug: 🔷 Lost 20% of their body fat 🔷 Gained lean muscle mass 🔷 Improved insulin sensitivity 🔷 And did all this without changes to diet or exercise This matters because most weight loss treatments, including GLP-1 medications, cause people to lose both fat and muscle. That’s not ideal. Muscle is metabolically active and plays a key role in long-term health. Bimagrumab works differently. It blocks proteins like myostatin and activin A that normally limit muscle growth. By removing those brakes, it allows the body to add muscle even as it burns fat. Any personal trainer will tell you this is incredibly difficult unless you’re a brand new trainee. Lilly sees the opportunity. A drug like this could help preserve strength and metabolic function during weight loss, especially in older adults or those already losing muscle. We often talk about “body weight,” but the more important metric is what that weight is made of. How much is fat. How much is muscle. That’s body composition. And changing it in the right direction could have far-reaching effects on health and longevity. The science is still developing. But $2 billion says this isn’t just a side story. It’s the next chapter.

Happy to share our latest publication, "Engineering Supramolecular Nanofiber Depots from a Glucagon-Like Peptide-1 Therapeutic"! As diabetes and obesity continue to rise, we aimed to build on the remarkable success of GLP-1 receptor agonists by redesigning these to form injectable depots through an engineered self-assembling peptide motif, forming a supramolecular nanofiber structure. This formulation demonstrated sustained release over several weeks in vitro and, in a rat model, maintained effective serum concentrations for over 40 days, resulting in reductions in blood glucose levels and weight gain—a promising step toward more convenient, long-lasting treatments for metabolic disorders. Special recognition goes to first author WEIKE CHEN, whose dedication was central to this project’s success. I’m also grateful to our talented co-authors—Sijie Xian, Bernice Webber, Emily DeWolf, Connor Schmidt, Rory Kilmer, Dongping Liu, and Elizabeth Power—for their invaluable contributions! If you're interested in new strategies for peptide-based therapies, check out the full paper here: https://lnkd.in/gVmESCeZ #DiabetesResearch #ObesityTreatment #DrugDelivery #SupramolecularChemistry #GLP1 #Therapeutics

Personalized obesity medicine study: Sometimes in medicine, we don’t fully understand why one treatment works for a patient while another doesn’t. I recently had a patient who lost 40 pounds on phentermine-topiramate—a powerful response. But after developing a contraindication, we switched to liraglutide, and then semaglutide. Unfortunately, she gained weight on both. A new study led by Dr. Andres Acosta and his team at Mayo Clinic may help explain why. They used a validated protocol to measure Calories to Satiation (CTS)—how much someone eats before feeling full—and found that individuals with high CTS responded better to phentermine-topiramate, while those with low CTS did better with GLP-1 receptor agonists like liraglutide. They also developed a genetic risk score (CTSGRS) that helped predict individual response. We don’t currently measure CTS or genetic risk in clinical practice—but maybe someday we will. This study is a strong step toward personalized obesity care. 👏 Congrats to Andres Acosta M.D., Ph.D. and his team on this important work. 💡 Just a reminder: my TEDx talk should be available this week! In it, I discuss why we need more research like this to better understand obesity and improve care. Here is a link to the article: #ObesityCare #PrecisionMedicine #GLP1 #PhentermineTopiramate #CTS #ObesityResearch #PersonalizedMedicine #TEDxNYULangone

𝐈𝐦𝐩𝐨𝐫𝐭𝐚𝐧𝐭 𝐔𝐩𝐝𝐚𝐭𝐞 𝐨𝐧 𝐎𝐛𝐞𝐬𝐢𝐭𝐲 𝐓𝐫𝐞𝐧𝐝𝐬 𝐢𝐧 𝐭𝐡𝐞 𝐔𝐧𝐢𝐭𝐞𝐝 𝐒𝐭𝐚𝐭𝐞𝐬: GLP‑1 receptor agonists — including Ozempic, Wegovy, Mounjaro, and Zepbound — have had a transformative impact on obesity management in the United States. Following a threefold increase in adult obesity rates from 1960 to 2021, recent U.S. health data now shows a modest but significant 2% decline from 2022 to 2025, a shift widely attributed to the rising use of GLP‑1 medications. The adoption of GLP‑1 drugs has accelerated rapidly. Between 2019 and 2024, prescriptions increased by nearly 587%, rising from 0.3% to 2.05% of overweight or obese adults. Usage has climbed particularly among women approaching menopause, with 18.6% of women on GLP‑1s using them for weight loss compared to 9.3% of men. Adherence rates are also improving. Nearly 63% of patients who began treatment with Wegovy or Zepbound in early 2024 remained on therapy after one year — a significant increase from 40% in 2023. Clinical trials report average weight reductions of 15–21% with semaglutide or tirzepatide over 12 months, outcomes comparable to some bariatric procedures. As a result, the volume of bariatric surgeries has declined, reflecting a shift toward medical rather than surgical obesity interventions. However, this may prove to be a temporary trend, depending on long-term efficacy, cost, and clinical practice guidelines for GLP‑1 use. Beyond weight loss, GLP‑1 therapies offer broader health benefits. These agents improve metabolic function, reduce systemic inflammation, and lower cardiovascular risk. Notably, the SELECT trial found a 19% reduction in all-cause mortality and a 20% reduction in cardiovascular deaths among patients treated with semaglutide. Despite these advances, significant barriers remain. Fewer than 3–4% of eligible obese adults currently receive GLP‑1 prescriptions, due to disparities in insurance coverage, cost, and geographic access. Out-of-pocket costs often exceed $1,000 per month, prompting some individuals to seek unregulated sources, which pose safety risks. Side effects are also a consideration. Common adverse effects include nausea, vomiting, and gastrointestinal discomfort. Long-term safety is still under review, particularly regarding risks of medullary thyroid cancer, gallbladder disease, and diabetic retinopathy. For this reason, baseline screening and ongoing monitoring are essential, especially in patients with diabetes or pre-existing thyroid conditions. GLP‑1 receptor agonists represent the first pharmacologic intervention with the potential to reverse national obesity trends. While challenges in access, cost, and long-term safety remain, these medications are already reshaping the landscape of obesity treatment in the United States — with implications for individual health and public policy for years to come. #obesitytrends #glp #hearthealth

Children's Hospital of Philadelphia Researchers Discover Molecule's Ability to Suppress Negative Effects of Type 2 Diabetes, Obesity. Findings, translated from a preclinical animal model into a human study, may serve as the basis for a potential therapeutic target for obesity-related type 2 diabetes. June 28, 2024 Excerpt: The new study revolves around macrophages, immune cells that remove dead cells and repair tissues. Adipose tissue macrophages (ATMs) keep adipose tissue, or body fat, healthy and functioning normally. While performing their essential functions, ATMs secrete small vesicles that contain important signaling molecules. Prior studies suggested normal ATM functions helped to prevent obesity-related metabolic disease, but the underlying mechanisms were poorly understood. Note: The key moment was discovering a micro RNA – a small noncoding RNA molecule responsible for controlling certain aspects of gene expression – called miR-6236. The researchers used a preclinical animal model to study the molecule’s function and how it helps to balance some of the harmful effects of obesity and type 2 diabetes at a cellular level. “This particular micro RNA had been previously mischaracterized, through two preclinical mouse models and a large data set of people at risk for metabolic disease. We were able to confirm the key role it plays in regulating insulin signaling,” said senior study author David A. Hill, MD, PhD, an attending physician and researcher with the Division of Allergy and Immunology at CHOP. “Findings like this show the immune system is central to a healthy metabolism, and hold promise for developing new treatments.” The study revealed miR-6236 is secreted by ATMs in cases of obesity. When the molecule was removed in a preclinical mouse model, several negative effects were observed, including adipose tissue insulin resistance, hyperglycemia, hyperinsulinemia, and hyperlipidemia. The researchers found miR-6236 improves insulin sensitivity by suppressing PTEN, a gene prior studies have linked to obesity and type 2 diabetes. In human samples, researchers found miR-6236 was among the most detectible micro RNAs found in serum of patients with obesity. It is thought ATMs secrete miR-6236 during obesity to improve insulin sensitivity and reduce the risk of hyperglycemia and glucose intolerance. Low levels of this molecule may indicate that patients have increased diabetes risk. Publication: Nature Communications Online June 25, 2024. Myeloid-derived miR-6236 potentiates adipocyte insulin signaling and prevents hyperglycemia during obesity.” https://lnkd.in/eD8NWPyK

More Pluses for GLP-1s 6/4/24 GLP-1 drugs have revolutionized the treatment of obesity demonstrating - in several RCTs - significant benefits for weight loss, diabetic control, as well as a reduction in strokes, heart attacks and cardiovascular-related deaths among people qualified to take them. Now, at the American Society of Clinical Oncology (ASCO), the largest cancer annual meeting in the world, several presentations are now suggesting 1) a reduction in the incidence of obesity related cancers like ovarian, liver, colorectal, pancreatic, bowel and breast cancer, and 2) a reduction in the recurrence of certain cancers. Whether their effects are due solely to the weight loss or associated with other mechanisms yet unknown - this is terrific news that will cement these group of drugs as the best sellers ever. While at present, only Wegovy, Ozempic (same Novo Nordisk drug, different indications), Mounjaro and Zepbound (same Eli Lilly drug, different indications) are available - numerous other agents are undergoing clinical trials. An oral agent (all others require injection) was recently proven to be very effective https://lnkd.in/eGDeaCck and it’s just a matter of time before we see this and other pill-form GLP-1s approved. #glp1 #cancer https://lnkd.in/exGBk9Mj

GLP-1s: The 20-Year "Overnight Success" Many people think GLP-1 medications are brand new, but they’ve actually been on the market since 2005. So why are they suddenly the hottest topic in weight loss and diabetes care? The answer lies in three major breakthroughs that changed everything: 📈 1. More Potent & Effective – Early GLP-1s weren’t nearly as powerful as they are today. The newer versions have dramatically improved results for both blood sugar control and weight loss. 💉 2. Easier Administration – In the beginning, GLP-1s required twice-daily injections. Then came once-daily options. Today, the most effective versions require just one injection per week, making them far more convenient. ✅ 3. FDA Approval for Weight Loss – Originally approved for type 2 diabetes, GLP-1s gained FDA approval for weight management, significantly expanding their use and popularity. These advancements explain why GLP-1s have gone from a niche diabetes treatment to a mainstream medical breakthrough that’s helping millions worldwide. The science keeps evolving, and so do the possibilities! #GLP1 #WeightLoss #DiabetesCare #HealthInnovation #WellnessRevolution I am Board Certified in Obesity Medicine, a Medical Chef, President of the Obesity Medicine Association, and Chief Medical Officer for Enara Health.

🔍 New Aon Analysis: GLP-1s Could Transform Workforce Health - - - 📊 Aon just released findings from a massive dataset—50M+ insured lives, 139K GLP-1 users—revealing that GLP-1 medications, when paired with holistic care, may bend the healthcare cost curve and boost workforce wellbeing. “GLP-1s paired with adherence support aren’t just a medical solution—they’re a business strategy.” —Farheen Dam, Head of Health Solutions, North America at Aon Key takeaways ⤵️ ✅ Slower Medical Cost Growth GLP-1 users saw a 7-point improvement in medical spend growth vs. matched controls by year 2—even after accounting for the initial Rx cost spike. ✅ Fewer Hospitalizations 💔 44% reduction in hospitalizations for major cardiovascular events (stroke, heart attack, heart failure). ✅ Broader Health Benefits Lower claims for pneumonia, IBD, osteoporosis, and substance use disorders. Slightly higher rates for arthritis and thyroid care—likely due to improved care engagement post-weight loss. ✅ Workforce ROI Potential If trends hold, expect gains in productivity, fewer sick days, and lower long-term health spend. 💬 What do you think—Are we ready to treat obesity like the chronic disease it is? Is your organization prepared to act? 📞To learn more about Accomplish Health’s comprehensive obesity benefit for employers, please contact Shelly Russell or reach out to me directly. - - - Announcement: https://lnkd.in/gtfcrabi #GLP1 #ObesityCare #FutureOfWork #HealthcareInnovation

Disruptive innovation - Biopharma style. In 1997, Clayton Christensen published his groundbreaking book describing how certain disruptive technologies reshape economies on a global scale. These technologies usually start as not so effective niche products, but with gradual improvements, overtake and destroy existing competitors that cling to older technologies that cannot adapt. Note in point here where GLP-1 drugs were made decades ago for diabetes but not potent nor convenient enough for adoption as a weight loss mechanism. With the rise of the new GLP-1 drugs from Novo and Lilly, incremental improvement led to a potent and convenient (chronic) way to treat diabetes, and morphed into an adjacent area of obesity. GLP-1 drugs continue to expand indications to heart disease, liver disease, and potentially neurological disease. In the process, the fashion industry, behavorial weight loss industry, and the packaged food industry were also highly impacted around the sequelae of GLP-1 mediated weight loss effects. In a different way, the GLP-1 effect is akin to the iPhone disrupting the camera industry, the map industry, news industry, entertainment etc. The latest update now is WW, formerly known as Weight Watchers, has succumbed to GLP-1 juggernaut as the behavorial modification company files for bankruptcy. Their attempts to turn around the company, to even offer online GLP-1, eventually failed. Plans are to emerge from bankruptcy and transform itself into a wellness based company. Founded in 1963, WW had a major run in weight control for nearly 60 years, but could not compete with pharmacological intervention. Read the fascinating history of WW here in the Guardian. https://lnkd.in/e6gR6Hxe