References

Website References

References Weight Loss vs. GLP-1

Novo Nordisk says that compound pharmacy semaglutides up to 33% impurities

Mechanisms of Action:

Delayed gastric emptying (feel full, not hungry)
Binds to and activates the GLP-1 receptor:
- Stimulates insulin secretion and inhibits the production of glucagon from pancreatic alpha cells if blood sugar levels are high
- Decreases pancreatic beta-cell apoptosis while promoting their proliferation. The consequences of this disruption of normal pancreas homeostasis is unknown.

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used to control high blood sugar in people with type 2 diabetes ¹. It works by mimicking the action of GLP-1, a naturally occurring hormone that helps to regulate blood glucose levels. By binding to and activating the GLP-1 receptor, it stimulates insulin secretion and lowers glucagon secretion when blood glucose levels are high. It also causes a slowing down in how fast the stomach empties ². This medication, administered through injection, helps people feel full for longer, helps regulate appetite, and reduces hunger and cravings.

However, semaglutide can have some side effects. The most common ones include ¹ ⁴ ⁵ ⁶:

Anxiety
Blisters on the skin
Bloating
Blurred vision
Chills
Cold sweats
Confusion
Cool, pale skin
Cough
Darkened urine
Depression
Diabetic Retinopathy
Difficulty swallowing
Dizziness
Extreme vomiting
Fast heartbeat
Fever
Gallbladder Disease
Gastroparesis (delayed emptying of the stomach)
Increased hunger
Large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
Loss of appetite
Nervousness
Nightmare
Pain in the stomach, side, or abdomen, possibly radiating to the back
Pancreatitis
Seizures
Skin rash
Slurred speech
Tightness in the chest
Trouble breathing
Unusual tiredness or weakness
Vomiting
Yellow eyes or skin

The EU has begun a probe into increased suicidal tendencies

Some Reference Articles and Summaries

Here are the key highlights from the article in bullet points:

GLP-1 receptor agonists like semaglutide have become hugely popular for weight loss and diabetes treatment due to their efficacy. However, as more people use them, rare but serious adverse effects are emerging.

A JAMA study found people taking GLP-1 agonists had a higher risk of pancreatitis, bowel obstruction, and gastroparesis compared to other weight loss medications. The GLP-1 group had a 9 times greater risk of pancreatitis, a 4 times greater risk of bowel obstruction, and a more than 3 times greater risk of gastroparesis, which causes stomach paralysis.

Reports of people aspirating or regurgitating food under anesthesia despite fasting prompted new guidance from anesthesiologists to stop GLP-1 agonists before surgery. Delayed stomach emptying and ileus may be contributing factors.

The European regulator is reviewing around 150 cases of possible self-injury and suicidal thoughts in GLP-1 agonist users to evaluate this potential safety signal.

Long-term risks like cancer are still unknown since these are meant for lifelong use, but rodent studies raise concern about medullary thyroid cancer.

Key takeaways for clinicians include starting low doses and slowly titrating up, monitoring for adverse effects, and engaging in shared decision making given the drugs don’t work for all.

As the class expands, more guidance is needed on safe use from professional societies.

Supply issues are prompting some to seek compounded versions, but these may not be safe or effective and the FDA warns against their use.

Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss

Here are the key highlights from the article in bullet points:

This study evaluated the risk of gastrointestinal adverse events associated with GLP-1 receptor agonists (semaglutide, liraglutide) used for weight loss compared to bupropion-naltrexone.

It used data from a large US health claims database including over 4,000 liraglutide users, over 600 semaglutide users, and over 650 bupropion-naltrexone users.

The outcomes examined were biliary disease, pancreatitis, bowel obstruction, and gastroparesis.

Incidence rates of all outcomes except biliary disease were higher in the GLP-1 agonist groups compared to bupropion-naltrexone.

GLP-1 agonist use was associated with a 9 times higher risk of pancreatitis, 4 times higher risk of bowel obstruction, and over 3 times higher risk of gastroparesis.

No significant increased risk was found for biliary disease with GLP-1 agonist use.

Sensitivity analyses excluding covariates or including GLP-1 agonist users without obesity diagnosis did not change the results.

Rare but serious gastrointestinal adverse events should be considered in discussions with patients given risks may differ for weight loss vs diabetes use.

The so called “miracle” weight loss drug not so miraculous after all

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