Browse the evidence

Tirzepatide is associated with a significantly increased risk of composite gallbladder or biliary diseases (including cholelithiasis, cholecystitis, and other gallbladder disorders) compared to placebo or basal insulin, but not compared to GLP-1 RAs.

Tirzepatide increases the risk of gallbladder or biliary issues (like gallstones or inflammation) compared to placebos or insulin. However, this risk appears similar to other GLP-1 medications. Be aware of symptoms like abdominal pain and report them to your doctor promptly, as early detection is key.

Use of GLP-1 receptor agonists (GLP1-RAs) is not associated with an increased risk of thyroid cancer compared to DPP-4 inhibitors in patients with type 2 diabetes.

If you have type 2 diabetes and are considering a GLP-1 medication like Ozempic or Wegovy, current large-scale evidence suggests it does not increase your risk of thyroid cancer compared to other common diabetes drugs. While rodent studies showed thyroid effects, this has not been observed in human population studies.

Administration of the ketone metabolite BHB-Phe (N-beta-hydroxybutyryl phenylalanine) suppresses food intake and reduces body weight in obese mice.

This research identifies a specific metabolite, BHB-Phe, which is naturally produced during ketosis and actively suppresses hunger. While the study used high-dose injections in obese mice, it suggests that maintaining ketosis may naturally elevate this compound, contributing to reduced food intake. For now, this is a mechanistic insight rather than a direct supplement recommendation, as oral bioavailability and dosing in humans are not established.

GLP-1 receptor agonists delay gastric emptying, increasing the risk of aspiration during anesthesia, necessitating specific preoperative discontinuation guidelines.

If you take Ozempic and have surgery, tell your surgeon. You likely need to stop the drug 1-7 days before surgery to prevent vomiting during anesthesia. Follow your doctor's specific instructions.

Dapagliflozin (SGLT2 inhibitor) lowers systolic blood pressure through an initial plasma volume contraction followed by a sustained reduction in sympathetic nervous system activity.

If you have type 2 diabetes and high blood pressure, dapagliflozin 10mg daily can help lower your blood pressure. It works by initially reducing blood volume and, over time, by calming the nervous system's stress response on your blood vessels. This happens even after the initial fluid loss stops.

Combining Dapagliflozin and Exenatide results in a synergistic blood pressure reduction that exceeds the sum of their individual effects, driven by plasma volume contraction and potentially other mechanisms beyond SNS reduction.

For patients with type 2 diabetes and obesity, combining dapagliflozin and exenatide offers a stronger blood pressure reduction than using either drug alone. This synergy helps achieve better cardiovascular protection, though the exact mechanism beyond fluid loss is still being studied.

Exenatide (GLP-1 RA) reduces parasympathetic nervous system activity, which may contribute to an increase in heart rate, but does not significantly lower systolic blood pressure on its own in this population.

Exenatide alone may not significantly lower blood pressure in people with type 2 diabetes and obesity, but it does reduce parasympathetic nervous system activity, which can increase heart rate. It is often used in combination with other drugs for better cardiovascular outcomes.

Tirzepatide does not increase the risk of major adverse cardiovascular events (MACEs) in patients with type 2 diabetes.

Tirzepatide does not increase the risk of major adverse cardiovascular events (MACEs) in patients with type 2 diabetes. This makes it a safe option for cardiovascular risk management.

SGLT2 inhibitors and GLP-1 receptor agonists reduce arrhythmia risk in diabetic patients by ameliorating intracellular sodium and calcium dysregulation and reducing fibrosis.

If you have type 2 diabetes, ask your doctor about SGLT2 inhibitors or GLP-1 agonists. These drugs do more than lower blood sugar; they help stabilize the electrical activity of your heart and reduce scarring, lowering your risk of sudden cardiac death.

Older anti-obesity medications (Orlistat, Sibutramine, Phentermine, Naltrexone/Bupropion, Phentermine/Topiramate) achieve mean weight loss between 5-10%, which is often insufficient to meet patient expectations and leads to lower long-term adherence.

Older anti-obesity medications (like Orlistat, Sibutramine, and combination drugs) typically produce 5-10% weight loss, which is beneficial but often fails to meet patient expectations, leading to higher discontinuation rates compared to newer agents.

Semaglutide is associated with an increased incidence of neoplasms (cancer) in clinical trials, specifically involving the thyroid, bladder, colorectal, and pancreas, although the absolute number of cases is often low and causality is not conclusive.

If you are taking semaglutide (Ozempic/Wegovy), be aware that clinical trials showed a small number of cancer cases, particularly in the thyroid, bladder, and pancreas. However, the paper notes this is not conclusive proof that the drug causes cancer, as obesity and diabetes themselves increase cancer risk. You should discuss your personal risk factors (especially family history of thyroid cancer) with your doctor.

GLP-1 receptor agonists (GLP-1RAs) cause a significantly higher rate of intolerable gastrointestinal adverse reactions leading to drug withdrawal compared to other hypoglycemic agents (Insulin, SGLT2i, DPP4i, TZD) and placebo.

If you are considering a GLP-1RA, expect a higher likelihood of gastrointestinal side effects (nausea, vomiting, diarrhea) compared to other common diabetes drugs like Metformin or SGLT2 inhibitors. These side effects are the most common reason for stopping the medication. However, not all GLP-1RAs carry the same risk; Dulaglutide appears to have the lowest risk of intolerable GI reactions, while Semaglutide and Liraglutide have higher risks, especially at higher doses.

Leptin analogs (metreleptin) are effective for treating obesity only in patients with generalized lipodystrophy or congenital leptin deficiency, but are ineffective and contraindicated for general diet-based obesity due to leptin resistance.

Leptin analogs like metreleptin are not for general weight loss. They are reserved for rare genetic conditions like generalized lipodystrophy where the body cannot produce leptin. For most people with obesity, leptin levels are already high, and adding more does not help.

MC4R agonists (setmelanotide) are effective for treating obesity in individuals with specific genetic deficiencies (POMC, PCSK1, LEPR) or Bardet-Biedl syndrome, but are not approved for general obesity.

If you have a rare genetic condition like POMC deficiency or Bardet-Biedl syndrome, ask your doctor about setmelanotide. It is a daily injection approved for these specific conditions. It is not approved for general obesity.

The association between ultra-processed food consumption and colorectal cancer risk is significant in men but not in women, and there is no significant association with prostate, rectal, pancreatic, or central nervous system cancers.

If you are male, be particularly mindful of UPF intake as it is linked to a higher risk of colorectal cancer. For women, the link to colorectal cancer was not statistically significant in this study. There was no significant link found for prostate, rectal, pancreatic, or brain cancers.

In individuals with type 2 diabetes and obesity, treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA) does not increase the risk of suicidal ideation or self-injury (SIS) compared to sodium-glucose cotransporter 2 inhibitors (SGLT-2i).

If you have type 2 diabetes and obesity, current evidence suggests that GLP-1RA medications do not increase your risk of suicidal thoughts or self-harm compared to other common diabetes drugs like SGLT-2 inhibitors. While regulators are reviewing safety data based on early reports, this large study found no such link. However, because these events are rare, the possibility of a small increased risk cannot be completely excluded, so monitoring your mental health remains important.

High-dose GLP-1 receptor agonists and treatment of patients with higher baseline BMI are associated with a significantly increased risk of ventricular arrhythmias (VAs).

If you are taking a high dose of a GLP-1 medication (like the maximum weight-loss doses of Ozempic or Saxenda), especially if you have a higher body weight, there is a slightly increased risk of ventricular arrhythmias. Doctors should monitor these patients more closely. However, this risk is specific to high doses and higher BMI, not the standard doses used for diabetes.

Oral semaglutide is associated with a significantly lower risk of incident atrial fibrillation (AF), while dulaglutide shows an increasing trend toward higher AF risk compared to controls.

Among GLP-1 medications, oral semaglutide (Rybelsus) may actually lower the risk of atrial fibrillation, while dulaglutide (Trulicity) might slightly increase it. This difference is drug-specific and not seen with all GLP-1s. If you have a history of AF, discuss the specific drug choice with your doctor.

GLP-1 receptor agonists (GLP-1 RAs) significantly increase the risk of gastrointestinal adverse events, specifically intestinal obstruction and perioperative aspiration, due to delayed gastric emptying.

If you are taking a GLP-1 medication (like Ozempic or Wegovy) and have surgery or an endoscopy, tell your medical team. You may need to adjust your fasting time or pause the medication to prevent stomach contents from entering your lungs, which is a known risk of these drugs.

GLP-1 receptor agonists are associated with an increased risk of gallbladder and biliary tract diseases, particularly with weight-loss focused dosing and specific agents like liraglutide.

Be aware that GLP-1 medications can increase the risk of gallstones, especially if you are losing weight rapidly. Report any abdominal pain to your doctor. This risk is higher with weight-loss doses compared to diabetes doses.

Current evidence does not support a significant increased risk of acute pancreatitis or pancreatic cancer associated with GLP-1 receptor agonists in human populations, despite early animal studies and spontaneous reports.

You do not need to worry about developing pancreatitis or pancreatic cancer from GLP-1 medications. Large studies have confirmed they are safe in this regard, although you should stop the medication if you experience severe abdominal pain.

Beta cell reserve and function are critical determinants of whether type 2 diabetes remission can be achieved and sustained, regardless of the amount of weight loss.

Even if you lose weight, your body's ability to produce insulin (beta cell function) determines if your diabetes goes into remission. This is why early intervention is crucial. If you have had diabetes for a long time, your beta cells may be too damaged to recover, even with significant weight loss.

Women experience a higher incidence of gastrointestinal adverse events (nausea, vomiting) from GLP-1 receptor agonists compared to men, even at similar drug exposure levels.

Women are more likely to experience nausea and vomiting from GLP-1 drugs than men. This is a known side effect. Use the recommended slow titration schedule to minimize these symptoms.

Tirzepatide 10mg and 15mg doses are associated with significantly higher rates of discontinuation due to adverse events compared to GLP-1 receptor agonists, primarily driven by gastrointestinal adverse events.

If you are using Tirzepatide at 10mg or 15mg, be aware that you are more likely to stop the medication due to side effects (like nausea or diarrhea) compared to using other GLP-1 drugs like semaglutide or dulaglutide. This risk is dose-dependent. If side effects become intolerable, discuss dose reduction or switching with your provider.