In recent years, new injectable medications like semaglutide (Wegovy and Ozempic) and tirzepatide (Zepbound and Mounjaro) have become very popular for weight loss. Often referred to as “skinny shots”, these drugs are properly known as GLP-1 receptor agonists (GLP-1 RAs, typically shortened to “GLP-1s” in the popular press). They work by mimicking a hormone in our body called GLP-1, which helps control appetite and blood sugar. GLP-1 naturally rises when we eat; it sends signals to the brain to tell us we’re full and to slow down our stomach emptying, both of which help us stop eating more. GLP-1 RAs’ popularity is understandable, as they’ve shown impressive results in clinical trials, helping people with obesity lose 15-21% of their body weight over about a year and a half.1,2
But what happens if you need to stop taking these medications? Let's explore why people might stop, what to expect, and how to plan for it.
Why Do People Stop Taking GLP-1 RAs?
For those battling overweight and obesity, it’s usually a lifelong struggle—much like any other chronic disease such as hypertension or diabetes. So it’s reasonable that doctors expect their patients to require long-term use of GLP-1 RAs to help them reduce weight and then maintain that weight loss. However, the reality is that even people taking them for diabetes—a disease that many regard as a more serious condition than obesity—are more likely to stop GLP-1 RAs than other diabetes drugs.3 So what are the main reasons people stop them?
Side Effects: The most common reason is stomach and intestinal issues like nausea, diarrhea, and vomiting. Such side effects were 1.5 times more frequent in the main semaglutide clinical trial.4 They were also more common in the main tirzepatide clinical trial: nausea by 3 times (occurring in 30% of those getting tirzepatide) diarrhea by over 4 times (in 30%) and vomiting by 5 times (in 10%).5 Less commonly, more severe digestive problems such as bowel obstruction, inflammation of the pancreas and complete loss of stomach emptying have occurred.6
Other side effects that have nothing to do with the stomach or bowel have also been reported, including hair loss (in around 5%) and mood changes.7
Cost: These drugs are expensive! In the US, they can cost up to $16,000 per year, and even at maximum discount can be over $6,500.8 What’s more, the majority of insurance plans don't cover them for weight loss.9 These high costs have led to the creation of many sites offering lower-cost versions, but in many cases, these are actually counterfeits or completely different medications. Buyers from such sites in Europe and elsewhere have been hospitalized for extremely low blood sugar, after injecting what they thought was a GLP-1 but turned out to be insulin, prompting global warnings for consumers to be wary.10
Supply Problems: Up until very recently there was a shortage of supply of both semaglutide and tirzepatide, due to high demand. Tirzepatide is apparently no longer in short supply (for now) though semaglutide still is. The supply problems of both these GLP-1 RAs led the FDA to list them officially in their shortage database, which means that compounding pharmacies can make their own versions. However, even though these compounded versions are ‘legal’ they are not actually approved by the FDA, and in some cases may include ingredient variations that have never been properly studied.
Needle Phobia: These drugs are given by injection just under the skin, which many people find painful or inconvenient.11 Users also complain about the size of the needle or (not surprisingly) would prefer to take them by mouth.11
Reaching Goal Weight: Some people stop once they've lost the weight they wanted to lose, even though rebound weight gain is common with GLP-1 RAs.
What Happens When You Stop GLP-1 RAs?
The biggest effect is rebound weight gain. Studies show that people who stop taking these medications often regain about half of the weight they’d previously lost, even though they continued to receive lifestyle coaching.12,13 In another study of people who stopped taking semaglutide and didn’t receive any dietary or exercise advice, they gained back over two-thirds of the weight.14 This can be frustrating and disappointing.
There's also a theory that these drugs might temporarily reduce your body's natural production of GLP-1. They flood the body with very high levels of synthetic versions of GLP-1 for extended periods of time, so it’s reasonable to suggest that the body doesn’t see any ‘need’ to make its own. If true, this could make weight gain even more likely when you stop the medication, because you’ve not only taken away what helped you lose weight, but you’ve also damped down your body’s natural production of ‘stop eating’ GLP-1.
Given all that, many people who start GLP-1 RAs may be quite anxious about stopping them. Nevertheless, there are strategies to help manage the aftermath of giving up these drugs.
How to Plan for Stopping
If you're considering these medications, it's important to have an ‘exit strategy’ before you start, to help you deal with the consequences of stopping them and to reduce any anxiety you may have about them. Here are some tips:
Focus on Lifestyle Changes: While taking GLP-1 RAs, work on developing healthy eating habits, regular exercise, and good sleep patterns. These will help you maintain your weight loss once you no longer use the injectables.
Get Support: Consider joining a support group or seeing a therapist to help you navigate the challenges of stopping the medication.
Set Realistic Expectations: It’s important to understand the journey of weight loss and maintenance (that’s it’s not a short one!) and that some weight gain is normal. Accept that long-term treatment of some sort may be necessary. Try to focus on your overall health, not just the number on the scale.
Consider Alternatives: What if you could kick-start your body back into making its own GLP-1 after you stop the injectables and even increase the usual amount of GLP-1 your body makes in response to eating? Calocurb® is an all-natural, plant-based supplement that does exactly that. It contains Amarasate®, which is a substance extracted from hops grown in New Zealand, where it’s been studied for over 14 years in multiple clinical trials (in humans, not lab animals). In one study, Calocurb taken an hour before eating caused GLP-1 to rise to 6 times baseline and twice the usual amount seen with eating—which resulted in the participants eating almost 20% less at the subsequent meal.15 And during 24-hour water fasts, overall hunger was reduced by 25% in men and by 30% in women.16,17 It’s been sold in New Zealand for over 5 years, where people have reported weight loss of up to 30 kg (around 60 lbs). Now there’s a new study underway looking at weight loss after taking Calocurb for 6 months (and then following up for a further 3 months).
Side effects with Calocurb are rare, but because up to 10% of users may get diarrhea, in general it should be started at a low dose and gradually increased over a few days, aiming to get up to 2 capsules before 2 meals a day. Some obesity doctors have already been advising their patients to start Calocurb in the same week as their last dose of their GLP-1 RA, in which case it’s not necessary to start the Calocurb as slowly.
Conclusion
Remember, obesity is a chronic condition, like diabetes or high blood pressure. It often requires long-term management, which may include ongoing medication. If you're thinking about starting or stopping these weight loss drugs, talk to your doctor first to create a plan that's right for you.
