GLP-1 Medications: How They Work, Uses & Side Effects

Mechanism

How GLP-1 Medications Work

GLP-1 (glucagon-like peptide-1) is an incretin hormone secreted by intestinal L-cells after meals. It stimulates glucose-dependent insulin release, suppresses inappropriate glucagon, slows gastric emptying, and acts on central satiety pathways in the hypothalamus and brainstem [6].

GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide) are synthetic, long-acting versions of this hormone resistant to rapid breakdown. Dual incretin agonists (tirzepatide) add GIP receptor activation, which appears to enhance insulin sensitivity and energy expenditure.

Once-weekly injectables dominate the modern market. An oral semaglutide tablet (originally Rybelsus, with a higher-dose 25 mg weight-loss formulation approved in 2025) is now available for patients who cannot or will not inject.

Indications

What GLP-1s Are FDA-Approved For

Type 2 diabetes — Ozempic (semaglutide), Mounjaro (tirzepatide), Trulicity (dulaglutide), Victoza (liraglutide), and oral Rybelsus (semaglutide) are approved as adjuncts to diet and exercise for glycemic control. Several also have FDA-approved cardiovascular-risk-reduction indications in patients with established cardiovascular disease.

Chronic weight management — Wegovy (semaglutide 2.4 mg), Zepbound (tirzepatide), and Saxenda (liraglutide) are approved for adults with BMI ≥30 or ≥27 with comorbidity. Wegovy is also approved for adolescents 12+ with obesity; Zepbound carries an additional indication for moderate-to-severe obstructive sleep apnea in adults with obesity.

Cardiovascular and metabolic — Wegovy is approved to reduce major adverse cardiovascular events in adults with overweight or obesity and established cardiovascular disease, based on the SELECT trial. Other indications (heart failure with preserved ejection fraction, kidney disease in diabetes) are being evaluated.

Effect Sizes

What Magnitude of Weight Loss to Expect

• ·Semaglutide 2.4 mg (Wegovy): ~14.9% mean weight loss at 68 weeks in STEP 1.
• ·Tirzepatide 15 mg (Zepbound): ~20.9% mean weight loss at 72 weeks in SURMOUNT-1.
• ·Tirzepatide vs. semaglutide head-to-head (SURMOUNT-5): tirzepatide produced significantly greater weight loss over 72 weeks.
• ·Liraglutide 3 mg (Saxenda): ~8% mean weight loss at 56 weeks — meaningful but smaller than newer agents.

Individual response varies substantially. About 10–15% of patients are non-responders; another 10–15% respond exceptionally well.

Safety

Class-Wide Side Effects & Risks

GI effects (nausea, diarrhea, vomiting, constipation, reflux) are universal across the class and dose-related. They peak during titration and are the primary reason patients discontinue.

Less common but important: acute pancreatitis, gallbladder disease, acute kidney injury from dehydration, hypoglycemia when combined with insulin or sulfonylureas, and rare reports of severe gastroparesis and bowel obstruction. Diabetic retinopathy complications have been observed with rapid glycemic improvement.

Boxed warning for rodent thyroid C-cell tumors applies across the GLP-1 class; personal or family history of medullary thyroid carcinoma or MEN2 is an absolute contraindication.

Loss of lean body mass is a class effect of rapid weight loss. Without adequate protein intake and resistance training, 25–40% of weight lost can be lean mass — which is why every GLP-1 prescription should sit inside a physician-led program.

Compounded GLP-1s

Compounded vs. FDA-Approved Products

Compounded semaglutide and tirzepatide marketed through telehealth and med-spas are not FDA-approved. The FDA has documented dosing errors, adverse events, and salt-form substitutions (semaglutide sodium, semaglutide acetate) that are not the same active ingredient as the brand-name medications [5].

Compounding became widespread during the 2022–2024 shortages of semaglutide and tirzepatide. With both drugs now off the FDA shortage list, the legal basis for routine compounding has narrowed substantially. Patients should know what molecule, what salt form, and what manufacturer they are actually receiving — and a board-certified physician should supervise any GLP-1 therapy.

Haute MD Standard

Why Physician-Guided GLP-1 Care Matters

GLP-1 therapy reshapes appetite, body composition, and metabolic risk simultaneously. Each of those can be mismanaged. A Haute MD–standard GLP-1 program is built on baseline labs, body-composition assessment, individualized titration, nutrition therapy that protects lean mass, structured resistance training, and a maintenance plan for after the loss phase. That is the line between medicine and a subscription.