Browse the evidence

Circadian disruption of clock genes (e.g., Bmal1, Per, Cry loss) leads to abnormal metabolic phenotypes, including hyperlipidaemia, hepatic steatosis, and impaired glucose tolerance.

Maintain a regular sleep-wake cycle and consistent meal times to support your body's internal clock. Disrupting this rhythm (e.g., through chronic shift work or erratic eating) may negatively impact your lipid and glucose metabolism.

Increasing age is inversely associated with cardiorespiratory fitness (CRF).

As you age, your cardiorespiratory fitness tends to decline. This is a common trend, but it is not a life sentence. You can counteract this decline by maintaining regular physical activity, which helps preserve your fitness levels and overall health as you get older.

Genetic disruption of core clock genes (e.g., Clock, Bmal1, Per) in mice leads to obesity, hyperphagia, and metabolic disorders, demonstrating a direct genetic link between circadian regulation and energy homeostasis.

Understand that your genetics play a role in how your body handles time and food. If you have a family history of metabolic issues, strict adherence to circadian hygiene (regular sleep/eating times) may be even more critical for you.

Peptide 20, a GIPR/GLP-1R/GCGR tri-agonist, achieves balanced potency across all three receptors through specific structural modifications, including lipidation of K10P, which stabilizes binding and enhances receptor-mediated cAMP accumulation.

Peptide 20 is a complex drug that activates three metabolic receptors (GIP, GLP-1, Glucagon) simultaneously. Its effectiveness relies on specific chemical modifications (lipidation) that stabilize the drug's binding to these receptors, leading to significant improvements in blood sugar, weight, and glucose tolerance in animal models.

Glucagon emergency kits (subcutaneous, intramuscular, or intranasal) are the standard of care for rapidly reversing severe hypoglycaemia in Type 1 Diabetes, with newer formulations offering faster resolution and ease of use.

If you have Type 1 Diabetes, keep a glucagon emergency kit (like Baqsimi or Zegalogue) accessible. In a severe low blood sugar emergency where the person cannot eat or drink, this medication rapidly raises blood sugar by signaling the liver to release glucose. Newer nasal and auto-injector versions are easier to use and work faster than older injection kits.

Leptin signaling via hypothalamic LepRbGlp1r neurons is the primary driver of food intake suppression, as ablating this receptor causes hyperphagic obesity without impairing energy expenditure.

This research identifies a specific brain pathway (LepRbGlp1r neurons) that leptin uses to tell you to stop eating. When this pathway is broken or ignored, you eat more regardless of how much energy you burn. This explains why some obesity treatments focus on mimicking these signals (like GLP-1 drugs) to restore the 'stop eating' signal rather than just forcing exercise.

SGLT2 inhibitors provide significant cardiovascular and renal protection in patients with type 2 diabetes, heart failure, and chronic kidney disease, independent of glycemic control.

If you have Type 2 Diabetes along with heart failure or kidney disease, SGLT2 inhibitors (like Jardiance, Farxiga, or Trulicity's cousin) are now a standard, first-line treatment. They protect your heart and kidneys regardless of your blood sugar numbers. Discuss starting one with your doctor immediately, as guidelines strongly recommend it for this specific patient profile.

Sodium glucose cotransporter 2 inhibitors (SGLT2i) significantly reduce the composite risk of cardiovascular death or heart failure hospitalization in patients with heart failure with preserved ejection fraction (HFpEF), regardless of diabetes status.

If you have HFpEF, ask your doctor about SGLT2 inhibitors (like empagliflozin or dapagliflozin). These drugs are proven to reduce the risk of heart failure hospitalization and cardiovascular death, even if you do not have diabetes. They are a standard part of modern treatment.

GLP-2 analogs are effectively used in the management of short bowel syndrome, reducing the need for parenteral support and improving patient quality of life.

For patients with short bowel syndrome, GLP-2 analogs are an effective treatment that can reduce the need for intravenous nutrition (parenteral support) and improve quality of life.

Glucagon remains essential for emergency hypoglycemia treatment.

Glucagon is an essential emergency treatment for severe hypoglycemia. Patients at risk should have access to glucagon kits and be trained in their use to ensure rapid and effective treatment of low blood sugar episodes.

Intensive glycemic control (targeting HbA1c ≤ 6.5%) does not significantly reduce cardiovascular events or all-cause mortality in patients with Type 2 Diabetes compared to standard control, and may increase mortality risk.

If you have Type 2 Diabetes, aiming for extremely low blood sugar (like an A1c under 6.5%) may not protect your heart and could actually increase your risk of death or severe low-blood-sugar episodes. Focus on standard control targets (around 7%) and managing blood pressure and cholesterol instead, unless your doctor advises otherwise based on your specific health history.

Intensive blood pressure control (targeting systolic BP < 120 mmHg) does not reduce fatal or nonfatal major cardiovascular events in patients with Type 2 Diabetes compared to standard control (< 140 mmHg) and increases adverse events.

If you have Type 2 Diabetes and high blood pressure, aiming for very low blood pressure (under 120 systolic) does not protect your heart more than standard targets (under 140) and may cause side effects like dizziness or kidney issues. Stick to standard guidelines unless your doctor specifies otherwise.

High-dose omega-3 carboxylic acid formulation (4 g/d) does not reduce major adverse cardiovascular events in high-risk patients with atherogenic dyslipidemia compared to corn oil.

For high-risk patients with high triglycerides and low HDL, adding 4g/day of omega-3 carboxylic acid to statin therapy does not reduce the risk of heart attack, stroke, or cardiovascular death compared to a placebo. This specific formulation and dose should not be relied upon for cardiovascular risk reduction in this population.

Empagliflozin (10 mg/day) does not significantly reduce the primary composite endpoint of hospitalization for heart failure or death from any cause in patients hospitalized with acute myocardial infarction.

Empagliflozin (10 mg daily) did not significantly reduce the risk of heart failure hospitalization or death in patients recently hospitalized for a heart attack, according to the EMPACT-MI trial. However, secondary analyses suggested some benefits in reducing heart failure events.

Overexpression of caveolin-1 in adipocytes increases caveolae density, enhances insulin-stimulated glucose uptake, and allows for larger lipid droplet storage.

This paper explains the cellular machinery behind fat storage. High levels of caveolin-1 help fat cells store more fat and process glucose better. This is a biological mechanism, not a direct advice for humans to manipulate, but it explains why some people store fat more easily than others.

A 12-week treatment with dulaglutide (1.5 mg weekly) does not improve long-term smoking abstinence rates compared to placebo when used as an adjunct to standard cessation therapy.

If you are trying to quit smoking, taking dulaglutide (Trulicity) alongside standard treatment (like Chantix/varenicline) will not increase your chances of staying smoke-free compared to standard treatment alone. Do not expect dulaglutide to help you quit smoking.

Obesity is a chronic disease driven by hypothalamic dysregulation of body fat mass set points, not by individual neglect of eating habits or exercise.

Stop blaming yourself for your weight. Your body is biologically defending a higher fat mass set point due to hypothalamic dysregulation. This is a chronic disease, not a moral failing. Effective treatment requires addressing this biology (e.g., via medications or surgery that target these pathways) rather than relying solely on willpower or calorie counting, which often fail because they trigger metabolic adaptation.

SGLT2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with type 2 diabetes, regardless of baseline ejection fraction or diabetes status.

If you have Type 2 Diabetes and Heart Failure (or are at high risk), ask your doctor about SGLT2 inhibitors (like Jardiance or Farxiga). These drugs are proven to significantly reduce the risk of being hospitalized for heart failure and dying from cardiovascular causes, regardless of your heart's pumping ability. They are now considered a standard part of treatment for this condition.

Resmetirom is the first FDA-approved drug for treating noncirrhotic nonalcoholic steatohepatitis (NASH) with moderate to advanced liver fibrosis, demonstrating efficacy in resolving NASH without worsening fibrosis and improving fibrosis by at least one stage without worsening NASH.

Resmetirom is now the first approved medication for NASH with fibrosis. It works by targeting thyroid hormone receptors to reduce liver fat and inflammation. Patients should discuss eligibility, specifically regarding fibrosis stage, with their healthcare provider, keeping in mind the high cost and the need for ongoing monitoring.

Thiazolidinediones (TZDs) increase the risk of hospitalization for heart failure through fluid retention mediated by sodium reabsorption.

If you have Type 2 Diabetes and Heart Failure, especially if it is moderate to severe (NYHA class III or IV), you should likely avoid Thiazolidinediones (like Actos or Avandia). These drugs cause fluid retention and significantly increase the risk of being hospitalized for heart failure. Your doctor will likely choose a different medication.

Females exhibit higher GLP-1 receptor (GLP1R) expression in specific brain regions (PBN, AP/NTS) involved in processing aversive stimuli, which may explain their heightened sensitivity to GLP-1 agonist-induced nausea.

This finding suggests that women's brains may have more 'targets' for GLP-1 drugs in areas that control nausea, which is why side effects are more common. This is a biological fact, not a personal failing.

SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) significantly slow the progression of diabetic kidney disease (DKD) and reduce cardiovascular events in patients with chronic kidney disease (CKD), regardless of baseline glycemic control or diabetes status.

If you have diabetes and kidney disease (or high cardiovascular risk), ask your doctor about SGLT2 inhibitors (like Jardiance, Farxiga, or Trjendi). These drugs protect your kidneys and heart, even if your blood sugar is already well-controlled. They are taken once daily. Be aware of potential genital yeast infections or, rarely, ketoacidosis, but these risks are generally manageable and outweighed by the protection they offer to your kidneys.

Sibutramine, a serotonin-norepinephrine reuptake inhibitor, was withdrawn from the European market because it significantly increases the risk of serious cardiovascular events (stroke, heart attack, cardiac arrest) without providing sufficient long-term benefit.

Sibutramine is no longer available in Europe because it was found to increase the risk of heart attacks and strokes. If you encounter it in illicit products imported from outside the EU, be aware that these products may be unsafe and unregulated. Always inform your doctor about any weight loss supplements you are taking.

GLP-1 receptor agonists induce nausea and vomiting primarily by binding to GLP-1 receptors in the dorsal vagal complex (brainstem) and stimulating peripheral vagal nerve fibers, leading to delayed gastric emptying and increased gut-to-brain signaling.

Nausea from GLP-1 medications is not a sign of toxicity or damage. It is a predictable side effect caused by how the drug interacts with your brain and gut nerves. This is why starting with a low dose helps your body adapt. The feeling is temporary and manageable, and it does not mean the medication is harming you.