Safety, Benefits and Side Effects of GLP-1 Weight Loss Medications 
According to a Pharmacist

GLP-1 medications, such as semaglutide in Ozempic/Wegovy and the newer GLP/GIP medication tirzepatide (Mounjaro/Zepbound), were originally developed to lower blood glucose in patients with type 2 diabetes. In addition to their significant A1C-lowering effects, the landmark clinical trials for these respective agents found substantial appetite suppression, less feeling of "reward" after eating, and subsequent weight loss. This led to further double-blinded, randomized, placebo-controlled trials examining the effects of semaglutide and tirzepatide in patients with obesity, but who did not have type 2 diabetes.

Research has shown GLP-1 medications caused side effects in both groups in the clinical trials and in patients after they entered the market. The most common side effects are nausea/vomiting, diarrhea and constipation. These tend to improve with extended use, yet can resurface as the doses of the medication are increased.

It must be said that there is no one-size-fits-all diet that must be prescribed when a patient is offered therapy with a GLP-1 or GLP/GIP medication. However, what one eats and how much one eats will likely affect the efficacy and tolerability of the medication. Given that these medications slow the speed at which stomach contents are moved farther down the gastrointestinal tract, bothersome side effects can be reduced by consuming smaller, though perhaps more frequent, meals. These new medications increase satiety, meaning the feeling of fullness or satisfaction after a meal. Eating past this point of satiety will likely lead to feelings of nausea and bloating.

It has also been observed that patients taking GLP-1 or GLP/GIP medications are at risk of losing lean muscle mass during weight loss, so it is important for patients to maintain adequate sources of protein in their diets.

Lastly—and this may be most important—it is essential to stay hydrated while taking one of these new medications, consuming at least two liters of water daily (unless otherwise directed by a physician). Not only will dehydration worsen side effects, such as constipation, acute dehydration can significantly harm one's kidneys, especially if he or she is already experiencing the early stages of chronic kidney disease.

Clinical trials have shown that after stopping the weight loss medication, patients tend to regain two-thirds of their weight back in one year. This is likely due to the fact that once the weight loss medication is stopped, patients do not feel satiated as quickly, frequent hunger returns, and previous food cravings come back.

There are a few conditions that would make a medication unsafe for a patient to take, when it comes to GLP-1s and GLP/GIP medications. The most commonly advertised contraindication is a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2. MTC is a rare thyroid cancer, and while a causative relationship between these medications and MTC has not been proven, MTC did develop in animals at clinically relevant doses during drug development.

These medications should also be avoided in patients with a history of acute or chronic pancreatitis, which is a painful and potentially fatal inflammation of the pancreas. If a patient already has slow stomach emptying, known as gastroparesis, a GLP or GLP/GIP should likely be avoided, as this condition will only worsen when the medication is started, often leading to intolerable side effects.

Lastly, if a patient is already experiencing damage to his or her eyes due to high blood sugar (called diabetic retinopathy), one should consult with their eye doctor before starting a GLP-1, especially semaglutide. Clinical trials have shown that rapidly improving blood sugar levels can worsen the existing eye damage in some patients.

GLP-1 and GLP/GIP medications differ from older weight loss drugs in many ways, but the most dramatic difference is in efficacy. Older weight loss medications would rarely result in more than 5% of weight loss from baseline and are typically not recommended to be taken for longer than three months. The new weight loss medications commonly result in weight loss ranging anywhere from 10% to 20% from baseline, with 25% weight loss observed in some of the latest clinical trials. Other key differences center around the way the medications work.

Many older weight loss medications tended to be stimulants, meaning they would suppress appetite by stimulating the central nervous system. This stimulation can lead to undesirable side effects such as insomnia, anxiety, and cardiovascular issues, including elevated heart rate and blood pressure.

To date, the only advantage possessed by older weight loss medications is that they are often more accessible and affordable, though they are accompanied with varied side effects and decreased efficacy compared to GLP-1 and GLP/GIP medications.