Browse the evidence

Activation of Glucagon-Like Peptide-1 Receptors (GLP-1R) in the Gustatory Cortex (GC) reduces homeostatic food intake in mice.

This research identifies a specific brain region (Gustatory Cortex) where GLP-1 receptors are active and influence how much we eat. While this doesn't change current dietary advice, it explains part of the mechanism behind GLP-1 based weight loss drugs, suggesting they work by altering how the brain processes taste and hunger signals, not just by signaling fullness from the gut.

The effect of GC GLP-1R activation on food intake is conditional on the palatability and fat content of the food, particularly in mice chronically maintained on a high-fat diet.

If you are trying to lose weight, switching from a high-fat diet to a lower-fat diet might make appetite-suppressing medications (like GLP-1 agonists) more effective. The brain's response to these drugs seems to depend on the palatability of the food, and changing your diet may help reset these signals.

GIPR agonism in humans may not provide weight loss benefits and can negate the appetite-suppressing effects of GLP-1.

While GIPR agonists work in animals, human studies show that adding GIP to GLP-1 can actually stop GLP-1 from working as well for appetite control. This suggests the human body responds differently than mice.

DPP-4 inhibitors (specifically Saxagliptin and Alogliptin) may increase the risk of hospitalization for heart failure, whereas Sitagliptin and Linagliptin appear neutral.

If you have Type 2 Diabetes and Heart Failure, be cautious with DPP-4 inhibitors. Saxagliptin and Alogliptin have been linked to an increased risk of heart failure hospitalization. However, Sitagliptin and Linagliptin have shown neutral effects. Discuss the specific risks and benefits with your doctor to choose the safest option for your heart.

GLP1R-expressing neurons in the human hypothalamus, specifically those co-expressing POMC in the arcuate nucleus and AVP in the paraventricular/supraoptic nuclei, are the primary neural targets mediating the appetite-suppressing effects of GLP-1 receptor agonists like semaglutide.

If you are using a GLP-1 medication like semaglutide, its ability to reduce your appetite is biologically grounded in its action on specific neurons in your hypothalamus (brain). This confirms that the reduction in food intake is a direct neurological effect, not just a side effect of slower digestion.

GIPR (Gastric Inhibitory Polypeptide Receptor) is expressed in human hypothalamic ependymal cells surrounding the third ventricle, suggesting a potential mechanism for how GIPR-targeting drugs like tirzepatide access the brain.

This research suggests that drugs targeting the GIP receptor (like tirzepatide) may interact with cells lining the fluid spaces in your brain. This provides a biological basis for how these medications might influence brain function related to appetite, beyond just their effects on the stomach.

Rare deleterious variants in the gene CORO1A are significantly associated with changes in BMI at the population level, identifying it as a novel genetic factor in obesity risk.

Genetic testing may reveal variants in the CORO1A gene that predispose individuals to higher BMI. This is a newly identified genetic risk factor.

Joining US Free Trade Agreements (FTAs) causes a statistically significant increase in the per capita sales of ultra-processed foods, processed culinary ingredients, and infant formula.

If you are involved in policy or public health advocacy, recognize that Free Trade Agreements with the US are a key driver of increased ultra-processed food and infant formula sales in partner countries. To protect public health, advocate for health exemptions in trade agreements, similar to tobacco carve-outs, to allow governments to regulate or tax these products without fear of legal challenges from corporations.

Second-generation oral contraceptive pill phase (active vs. inactive) does not influence muscle protein synthesis or myofibrillar proteolysis at rest or in response to resistance exercise.

If you take second-generation birth control pills, you can train for muscle growth without worrying about your pill cycle. Your muscles build and break down protein at the same rate whether you are on the active pills or the placebo week. Focus on your training and nutrition; the pill phase does not matter for your results.

Adding the long-acting PYY3-36 analogue PYY1875 (1.0 mg/week) to semaglutide (2.4 mg/week) yields only modest, non-clinically meaningful additional weight loss in people with obesity and is poorly tolerated due to gastrointestinal adverse events.

For individuals already on semaglutide, adding PYY1875 at 1.0 mg weekly provides only a small, likely unnoticeable additional weight loss benefit while significantly increasing the risk of gastrointestinal side effects like nausea. The 2.0 mg dose was not tolerated. Current evidence suggests this combination is not a viable strategy for improving weight loss outcomes due to poor tolerability and lack of clinical significance.

Concerns about side effects, long-term health risks, and potential for weight regain are significant barriers to patient interest in incretin-based anti-obesity medications, with higher endorsement of these barriers associated with lower interest in using the therapies.

If you are considering incretin-based weight loss medications, know that your concerns about side effects, long-term risks, and weight regain are common and valid. These concerns directly impact your interest in the treatment. To overcome these barriers, engage in open discussions with your healthcare provider about the relative risks of the medication versus the risks of untreated obesity, and inquire about support for lifestyle programs designed for medication users.

Endogenous peripheral GLP-1 enhances glucose-induced insulin release primarily through a vago-vagal reflex mediated by GLP-1 receptors on vagal sensory fibers, rather than through direct endocrine action on pancreatic beta-cells.

Your body's natural response to eating involves a complex gut-brain-heart axis. GLP-1 released from your gut doesn't just float to your pancreas; it signals your vagus nerve to help manage insulin. This highlights the importance of the neural connection between digestion and metabolic control, suggesting that factors affecting nerve health or gut signaling might influence metabolic efficiency.

Central GLP-1 produced by hindbrain PPG neurons and peripheral GLP-1 from intestinal L-cells regulate food intake through independent pathways, rather than acting synergistically or additively.

Your body uses two separate GLP-1 systems—one in your gut and one in your brainstem—to control hunger. They don't necessarily rely on each other. This means issues with gut hormone production might not directly impair your brain's satiety signals, and vice versa.

Using percent body weight loss as the sole target for obesity management is not ideal because it is often not feasible or sustainable for most participants and fails to capture holistic health outcomes.

Stop fixating on a specific percentage of weight loss as the only measure of success. For many people, achieving even a modest weight loss is not sustainable. Instead, focus on patient-centered outcomes like improved blood pressure, better glycemic control, and increased quality of life, which can be achieved through various lifestyle changes regardless of the final number on the scale.

Hepatic protein kinase Cbeta (PKCβ) deficiency mitigates late-onset obesity in mice by increasing energy expenditure through β3-adrenergic receptor signaling, independent of FGF21.

This research suggests that as we age, our liver may produce more PKCβ, which can suppress our body's ability to burn fat and heat (thermogenesis). While you cannot change your genetics, maintaining liver health through regular physical activity—which is shown to repress PKCβ expression—may help preserve your metabolic rate and resistance to age-related weight gain.

Physiological levels of GIP promote fat accumulation and insulin resistance in the context of high-fat diets and aging, acting as a 'thrifty hormone' that stores nutrients.

In the context of a high-fat diet, your body's natural GIP hormone helps store fat and may contribute to insulin resistance. This is why blocking GIP (antagonism) can help reduce obesity, while stimulating it pharmacologically (agonism) works through different mechanisms like appetite suppression in the brain.

Utilization of newer non-insulin glucose-lowering drugs (SGLT2 inhibitors and GLP-1RAs) has increased significantly in Australia, driven by cardiovascular and renal benefits, while older agents (sulphonylureas, glitazones) have declined.

If you have Type 2 Diabetes, talk to your doctor about newer medications like SGLT2 inhibitors or GLP-1RAs. These drugs not only lower blood sugar but also protect your heart and kidneys. While they are more expensive than older medications, they are increasingly recommended as first-line treatments due to these additional benefits.

Tirzepatide (5-15 mg weekly) does not increase the risk of adjudication-confirmed pancreatitis compared to placebo, insulin, or GLP-1 receptor agonists, despite causing greater elevations in serum pancreatic amylase and lipase.

If you are prescribed Tirzepatide for weight loss or diabetes, do not panic if your blood tests show higher pancreatic enzymes. The data shows this is a common side effect of the drug's mechanism but does not translate to actual pancreatitis. Routine monitoring is still advised, but the risk of clinical pancreatitis is no higher than with other standard treatments.

Switching antipsychotics to Aripiprazole results in significant weight reduction, but adding Aripiprazole to an existing regimen is not recommended due to increased risks of agitation and akathisia.

If you are gaining weight on your current antipsychotic, switching to Aripiprazole can lead to significant weight loss. However, do not simply add Aripiprazole to your current medication, as this can cause agitation and anxiety. Switching must be done carefully with your doctor, weighing the mental health stability against the metabolic benefits.

Under volume-matched conditions, increasing resistance exercise training frequency from once per week to five times per week does not increase daily myofibrillar protein synthesis rates in young men.

If you are trying to build muscle, you do not need to train each muscle group every day. As long as you are doing the same total amount of work (volume) and lifting with sufficient intensity, training a muscle once a week will build muscle just as effectively as training it five times a week. Focus on getting your total reps and sets in, rather than worrying about frequency.

Vertical sleeve gastrectomy (VSG) induces durable metabolic benefits and weight loss in nonhuman primates that are independent of caloric intake, mediated by early increases in bile acids and short-chain fatty acids, reduced visceral adipose tissue inflammation, and a polarization of immune cells toward regulatory phenotypes.

Vertical sleeve gastrectomy (VSG) is a highly effective intervention for obesity that works through complex biological mechanisms beyond simple stomach size reduction. It triggers early increases in beneficial metabolites (bile acids, short-chain fatty acids) and shifts the immune system in fat tissue to reduce inflammation and improve insulin sensitivity. These changes occur even if caloric intake remains the same, indicating that VSG fundamentally alters how the body regulates energy and metabolism. For patients, this means VSG offers durable metabolic benefits, including improved glucose control and reduced visceral fat inflammation, which are critical for long-term health independent of weight loss alone.

Increasing resistance training volume from moderate (3 sets/exercise) to high (5 sets/exercise) does not improve lean mass or muscle thickness preservation during a moderate caloric deficit in trained males.

If you are dieting to lose fat but want to keep your muscle, you do not need to drastically increase your training volume. A moderate volume (e.g., 3 sets per exercise) is just as effective as high volume (5 sets) for preserving muscle mass, provided you are eating enough protein (approx. 2.8g/kg FFM) and maintaining a moderate caloric deficit. Focus on keeping weights heavy (close to failure) rather than adding extra sets.

Initiating insulin glargine in patients with type 2 diabetes is associated with a higher risk of gastroparesis, intestinal obstruction, and all-cause mortality compared to initiating SGLT2 inhibitors.

If you are considering insulin glargine for type 2 diabetes, know that it is associated with a higher risk of gastroparesis, intestinal obstruction, and death compared to SGLT2 inhibitors. This does not mean insulin is bad, but it highlights the importance of choosing the right medication for your specific health profile. If you are at risk for GI issues, SGLT2 inhibitors might be a safer choice.

Knockout of the microprotein encoded by Adipocyte-smORF-1183 significantly impairs adipocyte differentiation and reduces lipid droplet formation.

This research identifies a specific, previously unknown protein (Adipocyte-smORF-1183) in mouse fat cells that is essential for storing fat. Knocking out this protein reduces fat storage by about half in these cells. While this is a fundamental biological discovery that could lead to future therapies for obesity, it is currently limited to cell culture models and does not yet translate to a direct human treatment or lifestyle intervention.