Glucagon-like peptide-1 (GLP-1) is a naturally occurring hormone produced in the gut, primarily by L-cells in the small intestine and colon, with smaller amounts from the pancreas and central nervous system. It is released in response to food consumption, typically within 10 to 15 minutes after eating. This hormone plays a role in regulating blood sugar levels by enhancing insulin secretion and reducing glucagon release in a glucose-dependent manner. Beyond its impact on blood sugar, GLP-1 also influences appetite and feelings of fullness, making it a focus for weight management.
How GLP-1 Contributes to Weight Loss
GLP-1 receptor agonists, which mimic natural GLP-1, promote weight loss through several physiological mechanisms. A primary way is by signaling to the brain to reduce hunger and increase satiety. This action occurs in brain regions that control appetite, such as the hypothalamus and brainstem, influencing neurotransmitter and peptide release.
Another mechanism involves delayed gastric emptying, which slows food movement from the stomach into the small intestine. This prolongs fullness after meals, leading to reduced caloric intake. The delay also helps control post-meal blood sugar spikes.
GLP-1 receptor agonists may also help reduce cravings for certain foods.
Achieving Weight Loss with GLP-1
GLP-1 peptides for weight loss lead to substantial reductions in body weight, as observed in clinical trials. For instance, studies have shown that semaglutide can result in approximately a 14.9% reduction in body weight over 68 weeks, while tirzepatide may lead to a 20.9% reduction over 72 weeks. Real-world data, however, indicates that average weight loss can be somewhat lower, with patients who maintained treatment for a year losing about 11.9% of their body weight, and those on high maintenance doses achieving 13.7% with semaglutide and 18.0% with tirzepatide.
GLP-1 medications are designed to be used in conjunction with lifestyle changes, not as a standalone solution. For optimal and sustainable results, a balanced diet focusing on protein, fiber, healthy fats, and regular physical activity is recommended. This combined approach supports muscle maintenance, helps manage appetite, and prevents weight regain.
Significant weight loss can be observed within six months to a year of consistent use. Long-term adherence to both the medication and lifestyle modifications is important for maintaining weight loss. Beyond weight reduction, individuals often experience other health improvements, such as better blood pressure, improved cholesterol levels, and reduced inflammation.
GLP-1 Medications and Their Use
GLP-1 receptor agonist medications approved for weight loss include liraglutide, semaglutide, and tirzepatide. Liraglutide is administered as a daily injection, while semaglutide and tirzepatide are typically given as once-weekly subcutaneous injections. Some formulations of semaglutide are also available as oral tablets.
These medications are prescription-only and require medical supervision. A healthcare professional will assess an individual’s suitability for these treatments, considering their overall health, medical history, and specific weight loss goals. Dosage is usually increased gradually over several weeks to help the body adjust and minimize side effects.
These medications are intended for individuals with a body mass index (BMI) of 30 or higher, or a BMI of 27 or higher with co-existing weight-related health conditions. They are part of a broader treatment plan that often includes dietary changes, exercise, and behavioral modification programs.
Important Safety Information and Considerations
GLP-1 medications are effective for weight loss but have associated side effects. Common side effects include gastrointestinal issues such as nausea, vomiting, diarrhea, constipation, and abdominal pain. These symptoms are often more pronounced when starting the medication or increasing the dose, but they tend to improve over time as the body adjusts.
More serious, rare side effects can occur. These include inflammation of the pancreas (pancreatitis), gallbladder problems such as gallstones, and kidney issues, particularly acute kidney injury. Dehydration due to severe gastrointestinal symptoms can worsen kidney problems. There is also a boxed warning regarding a potential risk of thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), observed in rodent studies, though human relevance is not definitively established.
GLP-1 medications are not suitable for everyone. They are contraindicated in individuals with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). They should also be used with caution or avoided in individuals with severe kidney impairment, a history of pancreatitis, or severe gastrointestinal diseases like gastroparesis.
Long-term use of GLP-1 medications is necessary for sustained weight management. Studies indicate that individuals who discontinue GLP-1 therapy may regain a significant portion of the weight they lost, with some studies showing two-thirds of lost weight returning within a year if lifestyle changes are not continued. Ongoing medical supervision is therefore essential for assessment, prescription, and continuous monitoring throughout the treatment period.