GLP-1 (glucagon-like peptide-1) is a hormone-like substance that has recently gained attention as a treatment for diabetes and weight loss. Originally developed to control blood sugar in type 2 diabetes patients, recent clinical trials have confirmed significant weight loss effects, expanding its use to obesity treatment. However, like all medications, it comes with side effects alongside its benefits. This article provides information about GLP-1's mechanism of action, real-world effectiveness, potential side effects, and practical guidance for safe use.

What is GLP-1?

GLP-1 is a natural hormone secreted by the small intestine, and one of the incretin hormones that are automatically released when blood sugar levels rise after eating. Under normal circumstances, GLP-1's blood concentration drops rapidly within minutes, but GLP-1 in medication form remains in the body longer and provides sustained effects.

Currently used GLP-1 receptor agonists include Liraglutide, Semaglutide, and Dulaglutide. Among these, semaglutide is administered as a weekly injection and has demonstrated an average weight loss effect of over 15% in clinical trials. Each drug differs in administration method (injection vs. oral) and duration of action, so they are selected based on the patient's condition.

How GLP-1 Works

GLP-1 acts on the body through three main mechanisms. First, it stimulates the pancreas's beta cells to increase insulin secretion. Since this only works when blood sugar is high, the risk of low blood sugar is relatively low. Second, it slows gastric emptying, allowing food to pass through the digestive system more slowly. This prolongs feelings of fullness and decreases appetite.

Third, it directly acts on the satiety center in the brain to suppress appetite. By binding to receptors in the hypothalamus, it reduces the desire for food intake. Due to these combined effects, patients naturally consume fewer calories. Research on GLP-1 patients showed that average daily calorie intake decreased by 400-500 kcal.

Additionally, GLP-1 inhibits hepatic gluconeogenesis, which lowers blood sugar and prevents excessive glucose production in the liver. With long-term use, it improves insulin sensitivity, helping the body respond better to insulin, and in diabetic patients, it can slow disease progression.

Side Effects of GLP-1

The most common side effects of GLP-1 are gastrointestinal symptoms. Nausea appears in approximately 30-40% of patients at initial treatment, and generally improves within weeks. Other reported side effects include vomiting (5-10%), diarrhea (20-30%), constipation, and abdominal discomfort. These symptoms occur due to the drug's characteristic of slowing gastric emptying.

More serious side effects include the risk of acute pancreatitis. While extremely rare, it is a serious adverse effect that requires immediate medical attention if persistent abdominal pain, nausea, or vomiting occurs. Additionally, due to the risk of medullary thyroid carcinoma, patients with a personal or family history of thyroid disease must consult with a specialist before treatment.

Other side effects include dehydration symptoms (particularly with diarrhea or vomiting), hypoglycemia (when used with other diabetes medications), and worsening of gallbladder disease. Additionally, drug-induced worsening of diabetic retinopathy has been reported in some patients, so careful monitoring is needed for those with diabetic retinopathy.

Effectiveness of GLP-1

In terms of blood sugar control, GLP-1 reduces HbA1c (glycated hemoglobin) by an average of 1.0-1.8%. This significantly lowers the risk of long-term complications in diabetic patients. Effects are particularly greater when used in the early stages before type 2 diabetes is diagnosed.

Improvement in cardiovascular health is also an important benefit. In major clinical trials (SUSTAIN series, SELECT trial, etc.), GLP-1 reduced the incidence of heart attack, stroke, and cardiovascular death by approximately 26%. This is thought to be due not only to weight loss but also to the drug's own anti-inflammatory and anti-atherosclerotic effects.

Weight loss effects are the most dramatic. High-dose semaglutide (2.4mg) achieved an average weight loss of 15.3% (approximately 15kg), with some patients losing over 20% of their body weight. Liraglutide shows relatively lower weight loss of 5-7%.

Additionally, GLP-1 slightly lowers blood pressure, reduces inflammatory markers (CRP, interleukins, etc.), and improves fatty liver disease. It is particularly known to significantly reduce hepatic fat content in patients with non-alcoholic fatty liver disease (NAFLD).

Genetic Factors

Individual responses to GLP-1 vary significantly based on genetic background. Polymorphisms in the GLP-1 receptor gene (GLP1R) explain individual differences in drug effectiveness and side effects. Patients with certain genetic variations show better blood sugar control at the same dose, while those with different genetic backgrounds may experience more side effects.

Genes related to insulin secretion capacity (such as TCF7L2) are also important. Genetic variations in these genes influence how well GLP-1 can stimulate remaining beta cells. Additionally, variations in genes related to energy metabolism and weight control (FTO, MC4R, TMEM18, etc.) cause individual differences in weight loss following GLP-1 treatment.

Patients with high obesity-related polygenic risk scores—those with genetic vulnerability to obesity—tend to respond better to GLP-1. This interesting finding suggests that patients with genetically more severe metabolic issues may benefit more from the drug. In the future, personalized medicine that can predict GLP-1 treatment response through genetic testing is expected to advance.

How to Preserve Muscle Mass During Weight Loss

The primary concern during GLP-1 treatment is loss of muscle mass during weight loss. When rapid weight loss occurs (especially 3kg or more per month), 25-35% of total weight loss can come from muscle. This can lower metabolic rate long-term and increase rebound risk.

First, adequate protein intake is essential. During weight loss, consuming 1.6-2.2g of protein per kg of body weight minimizes muscle loss. With GLP-1 treatment causing quick satiety, food choices are important. Prioritize high-protein foods like eggs, Greek yogurt, lean meat, fish, and legumes.

Second, resistance training is essential. Resistance training 2-3 times per week can reduce muscle loss by 40-50% during weight loss. Heavy weights are not necessary; exercises using body weight (push-ups, squats, lunges) or light dumbbell work are also effective.

Third, appropriately limit aerobic exercise. Excessive aerobic exercise accelerates muscle loss. Moderate-intensity aerobic exercise for 30 minutes or less, 2-3 times per week is appropriate.

Fourth, losing weight slowly is important. Aiming for 1-1.5kg monthly weight loss minimizes muscle loss. Since GLP-1 greatly reduces appetite, avoid excessive calorie restriction itself. Consuming above basal metabolic rate while gradually reducing weight is more effective.

Fifth, monitoring specific nutrients is necessary. During GLP-1 treatment, gastrointestinal absorption changes, so watch for deficiencies in vitamin B12, iron, and calcium. Supplementation is recommended when needed.

Conclusion and Summary

GLP-1 is a revolutionary medication for type 2 diabetes treatment and weight loss. It has many proven benefits including blood sugar control, cardiovascular protection, and dramatic weight loss. However, there are risks of nausea, gastrointestinal symptoms, and rare but serious side effects (pancreatitis, thyroid issues).

GLP-1's effectiveness varies individually based on genetic background, and personalized medicine is expected to allow prediction of drug response in advance. Particularly, patients carrying many obesity-related genes tend to show better treatment responses.

To avoid muscle loss during weight loss, adequate protein intake, regular resistance training, appropriate weight loss pace, and nutrient monitoring are essential. To emphasize: GLP-1 is only a medication and cannot completely replace lifestyle changes.

Important Medical Notice: GLP-1 must be used only under a healthcare professional's prescription and guidance. Self-medication, online purchase, or use without medical consultation is dangerous. Especially if you have thyroid disease, history of pancreatitis, or diabetic retinopathy, consult with a specialist beforehand. If severe abdominal pain, persistent vomiting, or hypoglycemic symptoms occur during treatment, visit a medical facility immediately.