The Lesser-Known Side Effects of Weight-Loss Injections

Obesity is a major global health problem and a risk factor for many chronic diseases. A new generation of drugs, GLP-1 receptor agonists, has brought fresh hope in the fight against obesity by playing an important role in weight management. However, awareness and management of the rare and sometimes serious adverse effects associated with these drugs are critical to successful treatment. This article addresses the potential adverse effects of GLP-1 receptor agonists and their implications for healthcare professionals and patients.

January 2023: An Important Milestone

The approval of the GLP-1 receptor agonist semaglutide for weight management (weight loss) in January 2023 marked the beginning of a new era in obesity treatment. In recent months, however, drug regulators have also documented rare, sometimes serious adverse effects associated with these agents' use in diabetes treatment. Some doctors may be unaware of these effects.

The following injectable drugs are approved by the FDA (US Food and Drug Administration) and used for weight loss:

Weight-loss injections and other weight-loss drugs may not be suitable for everyone and have adverse effects.

The most commonly reported adverse effects of weight-loss injections (GLP-1 receptor agonists) are:

1. Nausea: The most common adverse effect, which may appear when treatment begins and decrease over time.
2. Vomiting: Some users may vomit because of nausea.
3. Diarrhea: Diarrhea is common during use of these drugs.
4. Constipation: The drugs may affect bowel movements and cause constipation in some users.
5. Headache: Headache is a known adverse effect of GLP-1 receptor agonists.
6. Fatigue: Some users may experience fatigue or weakness while taking these drugs.
7. Loss of Appetite: Because the drugs work by suppressing appetite, users may feel less desire to eat.
8. Abdominal Pain: Some users may experience abdominal pain associated with the drugs.

New Information About the Adverse Effects of Weight-Loss Injections

When millions of people are treated with drugs such as semaglutide, even relatively rare adverse effects can occur in large numbers of individuals.

Despite the rarity of these adverse events and the possibility that benefits outweigh risks in severe obesity, doctors and patients need to be aware of these serious adverse effects.

GLP-1 receptor agonists, such as semaglutide and liraglutide, produce a feeling of fullness by mimicking certain gut hormones. Their adverse effects are mostly gastrointestinal: nausea, vomiting, constipation, and diarrhea. However, these are not the rare, serious adverse effects causing increasing concern.

Serious Stomach Problems

JAMA published a recent analysis showing that GLP-1 receptor agonists increased the risk of pancreatitis ninefold compared with an older weight-loss drug, bupropion. Bowel obstruction occurred four times more often and delayed stomach emptying three times more often in patients receiving GLP-1 receptor agonists. However, the absolute annual risks of these complications were below 1%.

Nevertheless, the absolute annual risks of these serious health problems remain below one percent. Although these drugs have known adverse effects such as acute pancreatitis and gallbladder disease, their effectiveness in weight management should not be forgotten. Despite a marked increase in the relative risk of rare, serious adverse effects, the overall risk of these complications remains low.

Anesthetic Complications

In spring 2023, reports appeared in scientific journals of vomiting or aspiration under anesthesia in patients using GLP-1 receptor agonists.

Notably, some patients vomited abnormally large amounts despite following doctors' instructions not to eat before surgery.

These problems are thought to result from GLP-1 receptor agonists slowing gastric emptying. The American Society of Anesthesiologists recommends not taking these drugs on the day of surgery and stopping weekly medications 7 days before surgery.

Increased Suicide Risk?

In July, the European Medicines Agency began reviewing 150 potential cases of self-harm and suicidal thoughts following reports of depression and suicidal ideation in patients taking liraglutide or semaglutide. The review now includes other GLP-1 receptor agonists, with results expected this month.

It is not yet clear whether the drugs caused these cases. However, suicidal thoughts and behaviors had also been observed with other obesity drugs, such as rimonabant. The need for caution and close monitoring in patients with a history of suicide is emphasized.

Long-term, even lifelong use of GLP-1 receptor agonists may be needed to maintain their effects on body weight. There is currently insufficient information about adverse effects and complications that may emerge over time when they are used for weight loss.

Other Considerations

Rodent studies have shown that GLP-1 receptor agonists may increase the risk of medullary thyroid carcinoma. Whether humans face a similar risk may take years to establish. Dulaglutide, liraglutide, semaglutide, and tirzepatide (a dual GLP-1/GIP receptor agonist) are contraindicated in patients with a history of medullary thyroid carcinoma.

Patients taking dual agonists (such as tirzepatide) or triple agonists (GLP-1/GIP/glucagon agents such as retatrutide) may lose more weight than those taking semaglutide alone. However, gastrointestinal adverse effects were more frequent in trials of these dual agonists.

Below is a mind-map diagram summarizing the article:

Awaiting Guideline Updates

Guidelines for using new GLP-1 receptor agonists remain limited. Existing clinical guidelines for obesity treatment were prepared before these drugs entered the market. Medical societies are currently working intensively on new guidelines to help doctors use these drugs safely and effectively in clinical practice. Updating the guidelines will make an important contribution to the effective and safe use of GLP-1 receptor agonists.

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