Glp-1
Episodes
Dariush Mozaffarian joins Dr. Rhonda Patrick to discuss dietary fats, ultra-processed foods, what fuels obesity, and the role of food as medicine.
Dr. Rhonda Patrick discusses nicotinamide riboside, biomarkers, belly fat loss, sex-specific health, curcumin & ashwagandha safety.
In this Aliquot, I discuss how these drugs work, their pros and cons, the latest research, and lifestyle strategies to...
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Nutrition Cancer Obesity Microbiome Heart Disease Diabetes Cholesterol Omega-3 Policy Fiber Polyunsaturated Fat Saturated Fat Dairy Carbohydrates Weight Loss Thermogenesis Brown Fat Ultra-Processed Foods Glp-1Dariush Mozaffarian joins Dr. Rhonda Patrick to discuss dietary fats, ultra-processed foods, what fuels obesity, and the role of food as medicine.
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Rhonda Omega-3 Biomarkers Inflammation Curcumin Bone Protein Exercise Epigenetics Aging Glp-1 UbiquinolDr. Rhonda Patrick discusses nicotinamide riboside, biomarkers, belly fat loss, sex-specific health, curcumin & ashwagandha safety.
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In this Aliquot, I discuss how these drugs work, their pros and cons, the latest research, and lifestyle strategies to...
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Rhonda Cancer Epigenetics Diabetes Mitochondria Calcium Dental Weight Loss Microplastics Glp-1 Ubiquinol Pollution PfasDr. Rhonda Patrick discusses GLP-1 agonists, alpha-lipoic acid, ubiquinone vs. ubiquinol, calcium needs, and liquid biopsy cancer screening.
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Dr. Rhonda Patrick explores creatine, dairy's effect on polyphenols, eggs' health impact, and new weight loss drugs like Ozempic in her latest Q&A.
Topic Pages
News & Publications
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Nearly one in six adolescents had a nutritional deficiency within a year of starting GLP-1 therapy. doi.org
Reducing food intake can help manage obesity and other metabolic disorders in adolescents, yet a growing body still needs adequate nourishment. Researchers investigated how often adolescents received a diagnosis of a nutrient deficiency or related complication after starting GLP-1 medication.
The study followed insurance records for 2,031 US adolescents for one year after their first GLP-1 prescription, using data from 2017 to 2022. Participants were 10 to 17 years old, and about two-thirds had type 2 diabetes. Researchers excluded anyone with a nutritional deficiency or related complication diagnosed in the prior six months. They then tracked new diagnoses and visits for nutrition therapy or counseling. However, the insurance records provided no information on actual dietary intake or laboratory results, and the study had no untreated comparison group.
- A nutrient deficiency or related complication was diagnosed in 10.2% of adolescents within six months and 16.8% within a year.
- Vitamin D deficiency was the most common diagnosis, recorded in 12.4% within a year. Other diagnoses included dehydration (2.6%), nutritional anemia (1.5%), and several less common deficiencies.
- Only 5.8% had a documented nutrition visit within 30 days, 23.3% within six months, and 38.3% within a year. Counseling not billed to insurance may have been missed.
GLP-1 drugs help manage weight by reducing appetite, but eating less can also make it harder to get enough essential nutrients. This is particularly important for adolescents, who need adequate protein, vitamins, and minerals to support healthy growth and development. However, because the study relied on recorded diagnoses rather than laboratory measurements, some deficiencies may have been present before treatment but only diagnosed afterward.
Weight loss and better blood sugar control are only part of managing obesity and its associated health risks. Adopting healthy lifestyle habits, including a balanced diet and regular physical activity, remains an essential part of treatment.
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Calorie restriction does more than reduce body fat; it also changes how cells maintain and repair themselves. Researchers investigated whether semaglutide, a GLP-1 receptor agonist widely used for weight loss, could reproduce some of those effects when given late in life.
The experiments began in female mice at 20 months of age. One randomized comparison followed 40 mice receiving daily semaglutide and 39 receiving inactive saline injections until their death. Separate mice underwent three months of treatment before tests of memory, physical abilities and glucose control, alongside cellular studies. To examine how reduced food intake could explain test results, another experiment assigned 10 mice per group to semaglutide, saline, or a 24% calorie-restricted diet for five months. That restriction matched the average drop in food intake with semaglutide.
- Median total lifespan reached 834 days with semaglutide versus 742 days with saline, a difference of 92 days or 12%.
- In the separate three-month experiment, semaglutide-treated mice had better spatial memory, coordination, muscle performance, endurance, and glucose control than saline-treated mice. The coordination and muscle-performance advantages remained after accounting for body weight.
- In the additional five-month experiment, both semaglutide and the calorie-restricted diet preserved movement, coordination, muscle performance, and endurance over the first four months, while saline-treated mice declined. Semaglutide and calorie restriction produced comparable reductions in weight and body fat.
- In that same experiment, semaglutide produced more favorable changes in spatial memory, exploratory behavior, and blood glucose control than the calorie-restricted diet.
One possible link between eating less and aging better is the work cells do to maintain their proteins. Proteins need the right shape to function, and cells use quality-control systems to help fold them or break them down. Semaglutide shifted gene activity toward this maintenance work and away from inflammation, changes that overlapped with those associated with calorie restriction. It also reduced signs of protein-folding stress in stem cells that produce blood cells and neurons. Semaglutide may help preserve tissue function as animals age by supporting this cellular upkeep, rather than simply reducing body weight.
Comparable reductions in body weight achieved with semaglutide or reduced access to food did not produce the same health benefits. Because GLP-1 receptors are found throughout the body, semaglutide may influence how tissues age in ways that go beyond reducing food intake.
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The biology associated with dementia extends beyond the brain to inflammation, metabolism, and blood-vessel health. Researchers investigated whether semaglutide could alter a blood-protein pattern linked to future dementia.
Researchers analyzed stored blood samples from 2,970 adults aged 65 or older who had participated in the randomized SELECT trial. All were overweight or obese and had established cardiovascular disease, but not diabetes. Participants received weekly semaglutide injections or matched placebo alongside standard care. Blood collected at the start and after 104 weeks was assessed with a model that uses 25 proteins to estimate the likelihood of a dementia diagnosis from any cause over five and 20 years. However, this secondary analysis did not systematically assess memory, thinking, or dementia diagnoses.
- Relative to their starting values, the predicted odds of dementia within five years were 26% lower with semaglutide than placebo at week 104. Risk estimates still rose in both groups, but less with semaglutide.
- For the 20-year dementia forecast, the predicted odds at week 104 were 8.8% lower with semaglutide than placebo relative to their starting values. The difference between treatments was smaller than for the five-year forecast.
- After accounting for changes in body mass index (BMI), 72% of the treatment-associated difference in the 20-year model remained.
- Semaglutide participants had 36% lower odds of being placed in a higher predicted risk category than placebo participants at week 104.
The protein score reflects processes throughout the body, including inflammation, metabolism, and blood-vessel function, not only changes within the brain. Semaglutide could affect this wider biology and thereby alter the pattern used to predict dementia. The drug mimics GLP-1, a hormone that helps the pancreas release insulin and the brain regulate appetite. But certain cells in the heart, blood vessels, and other tissues also carry GLP-1 receptors, allowing them to respond to the same signal. These additional targets offer possible ways for semaglutide to influence the protein pattern beyond the effects of eating less and losing weight.
A blood-protein score may help track how a treatment changes biology associated with dementia, not just estimate future risk. However, whether semaglutide's effect on the score actually reflects prevention must be tested in clinical trials designed to assess cognitive decline or dementia.
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Weight loss can look successful on the scale while concealing whether the body lost fat or muscle. Researchers tested whether raising ketone levels during treatment with semaglutide, the weight-loss drug sold under brand names such as Ozempic and Wegovy, could protect skeletal muscle without interfering with fat loss.
Male mice with diet-induced obesity and poor blood sugar control entered a three-week rapid-weight-loss experiment as they switched from a high-fat diet to regular food under calorie-deficit conditions. They were randomly assigned to inactive saline control injections, semaglutide, or semaglutide plus a ketone ester that raised blood ketones to levels that can occur naturally during fasting.
- The ketone ester preserved lean tissue during semaglutide-driven weight loss while allowing the same fat loss. As a result, the group receiving the combined treatment lost less weight overall but potentially retained more total muscle mass.
- Skeletal muscle weighed more and muscle fibers were larger with ketone cotreatment than with semaglutide alone.
- The ketone ester also protected grip strength and improved exercise endurance.
- Differences in total calorie intake did not explain muscle preservation. At the times when muscle loss was greatest, semaglutide-only mice consumed more total calories than the combination group.
Muscle requires a steady supply of usable energy to maintain and rebuild its proteins. During rapid weight loss, ketones can serve as an alternative fuel when energy from food is limited. In the semaglutide-only group, levels of several components of the cellular machinery for processing ketones and generating energy fell, while several gene signals tied to muscle protein breakdown rose. The ketone ester preserved these molecular patterns. Keeping ketone fuel available may therefore help muscle meet its energy needs and avoid shifting toward tissue breakdown. However, this remains a mechanistic interpretation rather than proof of the precise pathway.
Taken together, ketone cotreatment allowed semaglutide-treated mice to lose fat while retaining more muscle mass, strength, and endurance. The divergence suggests that the composition of rapid weight loss may depend on whether muscle can preserve the flexibility to switch toward alternative fuels when energy intake falls.
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Amino-acid restriction can improve metabolic health in animals, but old age makes the tradeoff sharper: restrict too much, and the diet may accelerate muscle loss and frailty. In these mice, methionine determined where restriction stopped helping and started harming.
Researchers fed genetically diverse male and female mice, beginning at 20 months of age, several diets that included low-amino-acid formulations with different methionine levels.
The moderate-methionine, low-amino-acid diet produced the broadest healthspan profile:
- It reduced fat mass and frailty, preserved lean mass, and improved glucose tolerance, insulin tolerance, and weight-adjusted grip strength.
- It lowered IGF-1 while raising growth hormone, GLP-1, and FGF21; without FGF21, much of the fat loss and improvement in insulin sensitivity disappeared. This places FGF21 near the center of the diet's metabolic effect.
- It did not significantly extend lifespan compared with the healthy control diet.
A separate analysis of adult dietary patterns found roughly twice the prevalence of type 2 diabetes among people with the highest versus lowest animal-protein intake. The estimate cannot isolate methionine from its food sources, and the mouse intervention does not support adding methionine to an ordinary or high-protein human diet.
Rather, the experiment reveals a narrow balance within amino-acid restriction: too little methionine increased frailty, whereas too much erased metabolic benefits. Methionine's effects appear to depend on the surrounding protein context and an intact FGF21 response, rather than being inherently beneficial or harmful. In a recent Q&A, Dr. Rhonda Patrick discussed why fasting-mimicking diets deliberately restrict protein while emphasizing strategies to preserve muscle.
Study coauthor Valter Longo has equity in L-Nutra, and several authors and USC hold or have licensed patents related to the dietary methods.
Press Release: Low-protein, amino acid-supplemented "longevity diet" linked to longer healthy lifespan, lower frailty risk, better metabolic health
Study: Methionine-supplemented longevity diet increases growth hormone, GLP-1, and FGF21; reduces frailty; and promotes healthspan -
Doctors have long wondered whether the heart benefits of the GLP-1 receptor agonist semaglutide (Ozempic®/Wegovy®) come only from helping people lose weight, or if the drug directly protects the cardiovascular system. An analysis of the SELECT trial explored this question in adults with cardiovascular disease and overweight or obesity, but without diabetes.
The study followed 17,604 participants aged 45 years or older across 41 countries for an average of more than three years. Each person was randomly assigned to once-weekly semaglutide (target dose 2.4 mg) or to placebo. Researchers recorded heart attacks, strokes, and cardiovascular deaths (collectively known as major adverse cardiovascular events, or MACE) and repeatedly measured body weight and waist circumference.
Here is what they found:
- Semaglutide lowered the risk of MACE by about 20% versus placebo.
- Early weight loss at 20 weeks did not predict lower subsequent MACE among those taking semaglutide; people who lost at least 5% of their body weight had similar event rates to those who lost less.
- In contrast, reductions in waist circumference at 20 weeks were associated with fewer subsequent events in the semaglutide group, possibly highlighting the importance of visceral fat loss (fat surrounding abdominal organs) rather than overall weight loss, which can also include lean mass such as muscle.
- Statistical modeling estimated that about one‑third of the treatment effect on MACE was mediated or marked by waist‑circumference reduction, while the remaining two-thirds came from other factors.
The researchers suggest that semaglutide's heart protection likely extends beyond weight or fat loss. By activating the glucagon-like peptide-1 receptor, the drug may directly influence blood vessel function, atherosclerotic processes, inflammation, blood pressure, and lipid metabolism. The authors note that adipose tissue can begin to change biologically before its overall mass declines, which might also help explain the early cardiovascular benefits seen in the trial.
The results show that patients with cardiovascular disease may benefit from semaglutide regardless of how much weight they lose, challenging prescribing rules that rely on body mass index thresholds or weight-loss targets. Future studies are needed to identify which biological processes drive these improvements and to determine whether similar benefits apply to broader populations. In Aliquot #128, I discuss how the new weight loss drugs like Ozempic® and Mounjaro® work, their pros and cons, and lifestyle strategies to optimize their effects for long-term health.
- Semaglutide lowered the risk of MACE by about 20% versus placebo.
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Semaglutide use reduces biological age by 3.1 years on average, with a 9% slower pace of aging as measured by DNA methylation. www.medrxiv.org
The biology of aging is increasingly seen as treatable, and drugs like semaglutide—once solely used for diabetes and weight loss—may be part of the solution. A recent study found that people with HIV who took semaglutide for 32 weeks experienced up to a 4.9-year reduction in biological age, as measured by changes in DNA methylation.
The study involved 84 adults with HIV-associated lipohypertrophy—a condition marked by excess abdominal fat and faster biological aging. Participants received weekly semaglutide injections or a placebo for 32 weeks. Researchers collected blood samples at the beginning and end of the study and analyzed DNA methylation, a type of molecular tag that shifts predictably with age.
Compared to those on placebo, participants taking semaglutide showed consistent reductions across several established epigenetic clocks, which estimate biological age from DNA patterns. One clock showed an average drop of 3.1 years, while another suggested a 9% slower pace of aging. Aging signals linked to inflammation, brain health, and heart function also declined in the semaglutide group, though measures of overall physical capacity remained unchanged.
These findings suggest that semaglutide influences more than metabolism—it may also target the molecular hallmarks of aging. Learn more about drugs like semaglutide in Aliquot #128: The Expanding Role of Weight Loss Drugs
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Type 2 diabetes and obesity increase a person's risk of developing dementia and other forms of neurodegeneration, particularly when the two conditions occur together. However, newer antidiabetes drugs may mitigate this risk. A recent study found that people taking the antidiabetes drugs semaglutide or tirzepatide were 37% less likely to develop dementia than those taking other diabetes medications.
Researchers analyzed electronic health records from more than 60,000 adults in the United States who had both type 2 diabetes and obesity. All participants began treatment with semaglutide, tirzepatide, or another type of antidiabetic medication between late 2017 and mid-2024. The researchers matched participants in the different treatment groups by age, sex, and health status and tracked their health for up to seven years.
People who took semaglutide or tirzepatide had a 37% lower risk of dementia, a 19% lower risk of stroke, and a 30% lower likelihood of dying during the study period than those on other antidiabetic drugs. These benefits were even greater among people over age 60, women, and those with a body mass index between 30 and 40. However, the risk of Parkinson's disease and brain bleeds did not differ between the groups.
These findings suggest that antidiabetes drugs like semaglutide and tirzepatide offer protection against cognitive decline and stroke, possibly extending life expectancy in people with type 2 diabetes and obesity. Semaglutide and tirzepatide are GLP-1RA drugs. Learn more about this class of medication in Aliquot #128: The Expanding Role of Weight Loss Drugs
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Age-related macular degeneration, the leading cause of irreversible blindness in older adults, affects nearly 200 million people worldwide. This progressive disease erodes central vision, which is critical for reading, driving, and other daily activities. A recent study found that glucagon-like peptide-1 (GLP-1) receptor agonists, such as Ozempic, Wegovy, or others, may double the risk of developing neovascular age-related macular degeneration, the most serious form of the disease.
Researchers analyzed health records from more than 1.1 million people in Ontario, Canada, who had diabetes and were 66 or older. They created a matched study group of about 139,000 people, comparing those who used GLP-1 receptor agonists for at least six months to similar patients who didn’t use the drugs. The researchers tracked new cases of neovascular age-related macular degeneration over three years.
They found that people who used GLP-1 receptor agonists were more than twice as likely to develop neovascular age-related macular degeneration than those who didn’t use the drugs. About 0.2% (93) of the users developed the condition, compared to 0.1% (88) of non-users. Even after accounting for other risk factors, the difference remained consistent.
These findings suggest that while GLP-1 receptor agonists provide considerable health benefits, they may also pose an overlooked risk for serious vision problems. It’s noteworthy that diabetes is an independent risk factor for macular degeneration, and this study identified associations, not a cause-and-effect relationship. Learn more about GLP-1 drugs in Aliquot #128: The Expanding Role of Weight Loss Drugs
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GLP-1 receptor agonists may lower risks for major illnesses like dementia and seizures. www.nature.com
Ozempic, Wegovy, and other glucagon-like peptide-1 (GLP-1) drugs have catapulted into the mainstream of diabetes care, with more than 15 million people in the U.S. currently taking one. Evidence suggests GLP-1 drugs have many off-target effects—both good and bad—but healthcare providers don’t currently know the full extent of the drugs' effects. However, a recent analysis found that GLP-1s may reduce the risk of dementia, seizures, respiratory illnesses, cardiometabolic disorders, and certain infections more effectively than other diabetes drugs and typical care.
Using the U.S. Department of Veterans Affairs healthcare databases, researchers identified roughly two million people with diabetes who were using a GLP-1 drug, one of three common anti-diabetes drugs (sulfonylureas, DPP4 inhibitors, or SGLT2 inhibitors), or continuing their usual care without adding new therapies. They tracked the participants' health for about 3.6 years.
They found that GLP-1 use was associated with a reduced risk of dementia (8%), seizures (10%), respiratory illnesses (10% to 25%), cardiometabolic disorders (7% to 22%), and certain infections (12% to 25%). However, the drugs were associated with an increased risk of gastrointestinal issues (5% to 20%), low blood pressure (10%), kidney problems (10% to 15%), arthritic disorders (10% to 16%), and pancreatitis (15% to 20%).
These findings suggest that GLP-1 receptor agonists offer promising benefits for people with diabetes while highlighting potential risks. Further research will illuminate the full range of the drugs' effects. Learn more about GLP-1 drugs in this clip featuring Dr. Rhonda Patrick.
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Appetite control varies widely with different weight-loss interventions. onlinelibrary.wiley.com
The body’s appetite feedback circuit is a sophisticated system that regulates hunger and satiety to maintain energy balance. Suppressing this circuit is essential to successful weight loss before reaching a plateau. A recent study found that weight-loss interventions vary in their capacity to overcome the body’s appetite feedback circuits by as much as threefold.
A researcher used a validated mathematical model to simulate the body’s weight-loss response to calorie restriction, glucagon-like peptide receptor agonists (GLP-1 RAs, a class of drugs primarily used to treat type 2 diabetes and obesity), and bariatric (gastric bypass) surgery. The model predicted how these interventions influenced body weight by simulating changes in caloric intake, energy use, and appetite over time.
He found that weight loss plateaued at around 12 months with calorie restriction and at around 24 months with GLP-1 RAs or gastric bypass surgery. The drugs and surgery were between 40 and 70 percent more effective at suppressing appetite than calorie restriction, aligning with data indicating that most people find calorie restriction challenging to adhere to, especially for an extended period.
These findings suggest that weight-loss interventions vary in their capacity to overcome the body’s appetite feedback circuits, influencing their effectiveness. Unfortunately, many people regain weight after successful weight loss, possibly due to changes in their gut microbiome. Learn more in this episode featuring Dr. Eran Elinav.
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Impairment of associative learning caused by obesity and insulin insensitivity offset by anti-obesity drug liraglutide in recent study www.sciencedaily.com
Associative learning is a psychological process that occurs when two initially unrelated elements, such as objects, sights, sounds, ideas, or behaviors, become linked in the brain. Classic examples include associating pain with touching a hot stove or connecting foodborne illness with eating a particular food. People with obesity and poor insulin sensitivity have impaired associative learning. However, a recent study shows that liraglutide, a drug used to treat type 2 diabetes and obesity, restores associative learning capability in people with obesity.
The study involved 54 adults, half with normal body weight (high insulin sensitivity) and half with obesity (reduced insulin sensitivity). Researchers gave participants either liraglutide or a placebo in the evening and tested their learning abilities the next morning.
They found that people with obesity and reduced insulin sensitivity encountered difficulties when attempting to establish connections between sensory signals, and their brain activity related to learning was weaker than in normal-weight individuals. However, just one dose of liraglutide reversed these issues in people with obesity and reduced insulin sensitivity, exhibiting brain activity comparable to that of normal-weight participants, indicating that the drug improved their learning abilities.
Liraglutide is a glucagon-like peptide 1 receptor agonist (GLP-1RA), a type of drug used to treat type 2 diabetes, overweight, and obesity. GLP-1RA medications work in the pancreas to lower blood glucose levels by promoting the production and release of insulin. They also support beta cells synthesis, growth, and survival while reducing their apoptosis rate.
These findings suggest that liraglutide, an anti-obesity drug, affects brain activity in people with obesity and reduced insulin sensitivity. This study was small, however, so validating the results requires more research.