Pros and cons of GLP-1 agonists for weight loss
8/14/2025 by David Brennan, M.D.
When you struggle to lose weight through diet and exercise alone, GLP-1 receptor agonists, medications like semaglutide (Wegovy) and tirzepatide (Zepbound), offer a powerful new tool. But before starting any treatment, it's important to weigh the benefits, drawbacks and alternatives to find what best fits your health goals and budget.
Pros:
- Effective, clinically-proven weight loss: People typically lose 10% to 15% of their body weight over several months, with some tirzepatide trials showing up to 20% at the highest doses.
- Better blood sugar control and metabolic health as these drugs mimic a hormone that boosts insulin release, reduces glucagon and slows gastric emptying, resulting in improved HbA1c, lowering insulin resistance, blood pressure and cholesterol.
- Appetite regulation and satiety: By acting on brain and gut receptors, GLP-1 agonists curb cravings and help you eat smaller, more satisfying meals, supporting long-term habit change. By decreasing "food chatter," many people find that they can better sustain healthy habits when willpower starts to wane.
Cons:
- High cost: Out-of-pocket expenses often run $800 to $1200 monthly, and weight-loss insurance coverage is inconsistent. Various direct-to-consumer programs, such as those offered by the drug makers, can lower the cost to around $500 per month. Other online companies offer "compounded" versions of the medications, but this is not a recommended route to obtain weight-loss medications.
- Potential for lifelong use: Studies have shown that most people who start weight-loss medications regain their weight after stopping the drug. Weight regain can be prevented or slowed by adherence to a healthy diet and regular exercise, but this doesn't work for everyone.
- Short-term gastrointestinal side effects: Medication initiation and dose increases commonly trigger nausea and vomiting, diarrhea or constipation, bloating and stomach discomfort, fatigue, dizziness, headaches, and injection-site redness or itching. These symptoms often improve as the body adapts to the treatment.
- Long-term side effects: Emerging data and concerns include:
- Loss of muscle mass: Over 30% of weight loss on medications can be from muscle. This is not too different from what is observed with any weight-loss method, but scientists are concerned that muscle is not always regained when weight is regained after stopping treatment.
- Reduced bone density: Sustained weight loss can accelerate bone mineral loss, raising fracture risk.
- Rare but serious risks: Pancreatitis, gallbladder disease, acute kidney injury and thyroid C-cell changes have been seen in animal studies.
- Uncharted decades-long effects: Potential neurocognitive, ocular (NAION optic neuropathy) or other organ-system impacts may only emerge with widespread, prolonged use.
Comparison to surgical and endoscopic weight loss
- Bariatric surgery, including gastric bypass and sleeve gastrectomy, achieves weight loss by 20% to 30%. This often leads to diabetes remission and improves comorbidities. Despite the $18,000 to $23,000 procedure cost, surgery is usually more cost-effective in the long term than GLP1 use.
- Endoscopic intragastric balloons are less invasive and have lower upfront costs with a 10% to 15% weight loss. Still, the benefits are typically temporary and not as cost-effective as surgery or combined approaches.
A personalized decision
GLP-1 agonists are revolutionizing obesity care but are not a one-size-fits-all solution. In primary care, clinicians partner with each patient to evaluate:
- Medication history and weight-related condition.
- Treatment goals (short-term versus long-term).
- Financial considerations and insurance coverage.
- Willingness to commit to lifestyle support (e.g., nutrition, exercise, behavior).
Whether you are exploring medication, surgery or non-surgical devices, talk to your primary care clinician to find the path that's right for you.
David Brennan, M.D., is a primary care physician in the Division of Community Internal Medicine, Geriatrics, and Palliative Care in Rochester, Minnesota. He focuses on prevention and treatment of a wide variety of common diseases.