GLP-1 glossary

503A compounding pharmacies operate under section 503A of the Federal Food, Drug, and Cosmetic Act. They prepare medications for individual patients in response to a valid prescription and are regulated primarily by state boards of pharmacy, with FDA oversight on quality. 503A pharmacies cannot legally compound copies of commercially available FDA-approved drugs except in narrow circumstances — historically including when the drug is on the FDA Drug Shortage List, or when there is a documented clinical need (e.g., patient allergy to an excipient).

503B outsourcing facilities are registered with the FDA under section 503B of the FD&C Act (added by the Drug Quality and Security Act of 2013). Unlike 503A pharmacies, they may produce compounded medications in bulk without patient-specific prescriptions for distribution to hospitals, clinics, and prescribers. They are subject to FDA inspection and current good manufacturing practice (cGMP) requirements. Many large telehealth platforms sourced compounded GLP-1s from 503B facilities during the shortage; this practice was sharply curtailed after the FDA shortage resolution in 2024-2025.

An autoinjector is a single-use, single-dose injection device that simplifies subcutaneous delivery. The user removes a cap, presses the device against the skin, and triggers the injection — typically completing in 5-10 seconds. Wegovy and Zepbound use single-dose disposable autoinjectors; Mounjaro uses a similar device. Ozempic and Saxenda use multi-dose refillable pens that require dialing the correct dose. Autoinjectors typically need refrigeration before use but can be at room temperature for a limited number of days (manufacturer-specific).

Beyond-use date (BUD) is the date or time after which a compounded sterile preparation should not be administered, set per USP <797> sterile compounding standards. Unlike commercial drug expiration dates that may extend years out, BUDs are typically 14, 28, or 45 days depending on the category of sterile compounding and storage temperature. Compounded semaglutide and tirzepatide multi-dose vials typically carry 28-45 day BUDs under refrigeration. Using a compounded medication past its BUD raises safety concerns including microbial contamination and potency loss.

BMI categorizes adults as underweight (<18.5), normal (18.5-24.9), overweight (25-29.9), obesity class I (30-34.9), class II (35-39.9), or class III (40+). FDA labels for chronic-weight-management GLP-1s (Wegovy, Zepbound, Saxenda) require BMI 30+ OR BMI 27+ with at least one weight-related comorbidity (hypertension, T2D, dyslipidemia, OSA, cardiovascular disease). BMI has known limitations — it does not differentiate fat from lean mass and misclassifies muscular individuals. Modern obesity medicine increasingly supplements BMI with waist circumference, body composition, and metabolic markers.

Body composition refers to the breakdown of body mass into compartments — fat mass, lean (skeletal muscle and organ) mass, bone mineral, and water. It is measured via DEXA scan, BIA, hydrostatic weighing, or air displacement plethysmography. With GLP-1-induced weight loss, fat:lean ratio of loss is roughly comparable to other caloric restriction methods (60-75% fat / 25-40% lean), though this remains an active research area. Resistance training and adequate protein intake (1.2-1.6 g/kg/day) are widely recommended to preserve lean mass during GLP-1 therapy.

A boxed warning (sometimes called a 'black box warning') is the most prominent warning the FDA can require on a drug label, highlighting serious or life-threatening risks. All currently marketed GLP-1 receptor agonists carry a boxed warning about thyroid C-cell tumors — specifically medullary thyroid carcinoma — observed in rodent studies. The clinical significance for humans remains unclear, but the warning contraindicates use in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN2).

Compounded semaglutide is semaglutide prepared by a 503A or 503B compounding pharmacy, often combined with vitamin B12, B6, or glycine. It is NOT FDA-approved as a finished product. Compounding was permissible while semaglutide was on the FDA Drug Shortage List (May 2023 to February 2025). Once the FDA declared the shortage resolved in February 2025, mass compounding by 503B outsourcing facilities was phased out by April 22, 2025, and most 503A pharmacy compounding was tightly restricted to bona fide patient-specific clinical needs. Some semaglutide salts (semaglutide sodium, semaglutide acetate) were specifically flagged by FDA as unsuitable. Quality, sterility, and potency vary by pharmacy.

Compounded tirzepatide is tirzepatide prepared by a 503A or 503B compounding pharmacy. It is NOT FDA-approved as a finished product. Tirzepatide was on the FDA Drug Shortage List from December 2022 to October 2024. Following the FDA's October 2024 declaration that the shortage was resolved, 503B outsourcing facilities were prohibited from compounding tirzepatide after March 19, 2025, with 503A pharmacies subject to tighter scrutiny. Eli Lilly has actively pursued legal action against pharmacies and telehealth platforms continuing to distribute compounded tirzepatide.

Cost per pound (lost) is a back-of-envelope economic comparison metric calculated as total medication and program cost divided by total weight loss in pounds. At full retail (no insurance, no manufacturer savings), Wegovy at roughly $1,350/month and 14.9% TBWL gives a cost per pound of about $250-400 depending on starting weight. Tirzepatide tends to score better per pound due to greater efficacy. Compounded versions can be substantially cheaper per pound but carry quality and regulatory uncertainty. The metric does not capture quality of life, comorbidity reduction, or long-term value.

Dipeptidyl peptidase-4 is a serine exopeptidase expressed on cell surfaces and circulating in plasma. It cleaves the N-terminal dipeptide from incretin hormones, inactivating GLP-1 and GIP within 1-2 minutes of release. DPP-4 inhibitor drugs (the 'gliptins' — sitagliptin/Januvia, linagliptin/Tradjenta, saxagliptin) modestly increase endogenous incretin levels but do not produce the supraphysiologic GLP-1 effect of injectable GLP-1 RAs, and their weight and HbA1c effects are smaller.

A dual agonist is a single molecule that binds and activates two distinct receptors. Tirzepatide is the first FDA-approved dual GIP/GLP-1 receptor agonist, leveraging both incretin pathways. Multiple dual and triple agonists are in development, including retatrutide (GIP/GLP-1/glucagon triple agonist by Eli Lilly, phase 3) and survodutide (GLP-1/glucagon by Boehringer/Zealand). These next-generation incretin-based therapies aim to push weight-loss efficacy further while potentially preserving lean mass.

The FDA Drug Shortage List identifies drug products that are in supply shortage, as defined under the Food and Drug Administration Safety and Innovation Act. Inclusion on the list provides certain regulatory flexibilities, including allowing 503A and 503B compounding pharmacies to compound copies of those drugs during the shortage period. Tirzepatide was removed from the shortage list in October 2024; semaglutide was removed in February 2025. Removal triggered phased deadlines for compounders to cease production, with 503B facilities subject to faster deadlines than 503A pharmacies.

Food noise is the colloquial term for persistent, intrusive cognitive preoccupation with food — thoughts about what to eat next, cravings, planning meals, and difficulty disengaging from food cues. While not a formal clinical construct, it overlaps with concepts of hedonic hunger, reward-driven eating, and food cue reactivity. Patients on GLP-1 RAs widely report that food noise quiets dramatically within days to weeks of starting, and that it returns when the medication is stopped. Researchers are increasingly studying this phenomenon as a potential mediator of GLP-1 weight-loss efficacy.

A formulary is the list of prescription drugs covered by a health insurance plan, organized into tiers determining patient cost-sharing. Tier 1 (generic) has the lowest copay; Tier 4-5 (specialty) the highest. GLP-1 RAs are typically Tier 2 (preferred brand) or Tier 3 (non-preferred brand), often with prior authorization, step therapy, and quantity limits. Formularies update annually (sometimes quarterly) — drugs may move tiers, be added, or be removed. Patients should verify formulary placement before assuming coverage.

Gastric emptying is the gradual passage of partially digested food (chyme) from the stomach into the duodenum. Normal half-emptying time is roughly 30-90 minutes depending on meal composition. GLP-1 RAs significantly slow gastric emptying, an effect strongest at initiation and partially attenuated with chronic dosing. Slowed emptying contributes to satiety and post-meal glucose smoothing but also drives nausea, bloating, early satiety, and in rare cases gastroparesis. The American Society of Anesthesiologists issued guidance (2023) on holding GLP-1s before elective procedures due to aspiration risk.

Gastroparesis is a chronic motility disorder characterized by delayed gastric emptying without mechanical obstruction, producing nausea, vomiting, bloating, early satiety, and abdominal pain. GLP-1 RAs slow gastric emptying as part of their pharmacology, and a subset of patients develop severe, prolonged delayed emptying that meets clinical gastroparesis criteria. The FDA updated Ozempic labeling in 2023 to note potential ileus/severe gastric emptying issues. Patients with pre-existing gastroparesis or severe GI motility disorders may be at higher risk and should discuss alternatives with a physician.

Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino-acid incretin hormone secreted by intestinal K-cells in response to nutrient intake. GIP stimulates insulin secretion in a glucose-dependent manner and influences lipid metabolism in adipose tissue. Together with GLP-1, GIP accounts for the incretin effect — the amplified insulin response to oral vs IV glucose. Tirzepatide is the first FDA-approved dual GIP/GLP-1 receptor agonist; pure GIP agonists and antagonists are in pipeline development.

Glucagon-like peptide-1 is a 30-amino-acid incretin hormone secreted by intestinal L-cells in response to food intake. It binds the GLP-1 receptor on pancreatic beta cells to stimulate glucose-dependent insulin secretion, suppresses glucagon from alpha cells, slows gastric emptying, and acts on hypothalamic centers to promote satiety. Native GLP-1 is degraded in 1-2 minutes by DPP-4. Pharmaceutical GLP-1 receptor agonists are modified to resist degradation, extending half-life from minutes to days.

GLP-1 receptor agonists (GLP-1 RAs) are synthetic peptides that bind and activate the GLP-1 receptor with much longer half-lives than native GLP-1. The class includes semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), and exenatide (Byetta, Bydureon). Most are once-weekly subcutaneous injections; Rybelsus is oral; liraglutide and exenatide are daily/twice-daily. Several have FDA-approved cardiovascular outcomes indications.

Glucose-dependent insulin release is a property of incretin hormones (GLP-1, GIP) and their pharmaceutical mimetics — they amplify insulin secretion from pancreatic beta cells only when blood glucose is elevated. This contrasts with sulfonylureas (glipizide, glimepiride), which trigger insulin release regardless of glucose level. The glucose-dependent mechanism explains why GLP-1 RAs as monotherapy carry very low hypoglycemia risk, while combination with insulin or sulfonylureas substantially increases that risk.

Hemoglobin A1c is the percentage of hemoglobin molecules with glucose attached, reflecting average blood glucose exposure over the lifespan of red blood cells (about 120 days). It is the standard diagnostic test for diabetes (HbA1c 6.5%+), prediabetes (5.7-6.4%), and ongoing glycemic monitoring. GLP-1 RAs lower HbA1c through glucose-dependent insulin release, glucagon suppression, and weight loss — typical reductions are 1.0-1.5 percentage points for semaglutide and up to 2.3 points for tirzepatide at maximum doses.

Hypoglycemia is blood glucose below the normal range, typically defined as <70 mg/dL, presenting with shakiness, sweating, palpitations, confusion, and in severe cases loss of consciousness. GLP-1 RAs work in a glucose-dependent manner — they amplify insulin release only when glucose is elevated — so monotherapy hypoglycemia is rare. However, combination with insulin or insulin secretagogues (sulfonylureas like glipizide, glimepiride) substantially increases hypoglycemia risk. Dose reductions of insulin or sulfonylurea are typically recommended when initiating a GLP-1.

Incretins are a class of metabolic hormones secreted by intestinal endocrine cells in response to nutrient ingestion. The two principal incretins are GLP-1 and GIP, which together account for 50-70% of post-prandial insulin release in healthy individuals. The incretin effect is blunted in type 2 diabetes. The therapeutic recognition of this physiology spawned the entire GLP-1 RA drug class as well as DPP-4 inhibitors (which prolong native incretin action).

Insulin resistance is reduced cellular sensitivity to insulin's signal, leading to compensatory hyperinsulinemia and eventually beta-cell exhaustion. It is measured indirectly via HOMA-IR (fasting insulin x fasting glucose / 405) or glucose tolerance testing. Insulin resistance is the central physiological derangement in metabolic syndrome, PCOS, NAFLD, and prediabetes/T2D. GLP-1 therapy improves insulin sensitivity through weight loss and direct hormonal effects, typically reducing HOMA-IR scores by 30-50% in trial populations.

Lean body mass (LBM) is total body mass minus adipose tissue, encompassing skeletal muscle, organs, bones, blood, and lymphatic tissue. Skeletal muscle alone is sometimes reported as fat-free mass (FFM) or lean muscle mass. During any significant weight loss — surgical, dietary, or pharmacologic — some lean mass is lost. To minimize lean mass loss on GLP-1 therapy, clinical guidance suggests 1.2-1.6 g/kg/day of dietary protein and 2-3 resistance training sessions per week. Aging adults are at higher risk of sarcopenia and may need additional monitoring.

LillyDirect is Eli Lilly's direct-to-consumer platform offering Zepbound, Mounjaro, and other Lilly medications. It includes a telehealth pathway via independent providers, direct pharmacy dispensing, and the 'Zepbound vial program' launched in 2024 — single-dose vials at lower prices for self-pay patients (starting around $349/month for 2.5 mg and scaling with dose). LillyDirect explicitly does not accept insurance for the vial program, which is positioned as a competitor to compounded tirzepatide.

Liraglutide is a long-acting GLP-1 analog with a half-life of approximately 13 hours, requiring once-daily subcutaneous injection. Victoza is FDA-approved for type 2 diabetes in adults and children 10+; Saxenda is approved for chronic weight management in adults (BMI 30+ or 27+ with comorbidity) and pediatric patients 12+. Liraglutide produces less weight loss (5-8% TBWL) than semaglutide or tirzepatide. A generic version of liraglutide became available in 2024.

The maintenance dose is the steady, ongoing dose a patient continues after titration is complete. For Wegovy, maintenance is 2.4 mg subcutaneously once weekly (with 1.7 mg as a fallback for tolerability). For Zepbound, maintenance is individualized at 5, 10, or 15 mg once weekly. For Ozempic in T2D, maintenance is 0.5, 1, or 2 mg weekly. Some patients respond well at lower maintenance doses; others require the maximum. Reaching maintenance does not mean weight loss is complete — the plateau effect typically arrives 12-18 months in.

Manufacturer savings cards are direct-to-patient copay assistance programs that reduce out-of-pocket cost for commercially insured patients. Novo Nordisk's Wegovy and Ozempic savings cards can reduce eligible patients' copay to as low as $0-25/month (with annual caps and coverage requirements). Eli Lilly's Zepbound and Mounjaro savings cards work similarly. Federal-payer (Medicare, Medicaid, TRICARE, VA) patients are excluded by federal anti-kickback rules. Eligibility, caps, and terms change frequently — verify current details on the manufacturer's website.

Multiple Endocrine Neoplasia type 2 (MEN2) is an autosomal dominant disorder caused by mutations in the RET proto-oncogene. It predisposes to medullary thyroid carcinoma (nearly 100% lifetime risk), pheochromocytoma, and (in MEN2A) parathyroid adenoma. Because all GLP-1 RAs carry a boxed warning about thyroid C-cell tumors observed in rodents, personal or family history of MEN2 (or medullary thyroid carcinoma) is a labeled contraindication for all currently marketed GLP-1 receptor agonists.

NovoCare is Novo Nordisk's umbrella patient support program covering Ozempic, Wegovy, Rybelsus, Saxenda, and other Novo medications. It includes manufacturer savings cards for commercially insured patients, patient assistance programs for low-income/uninsured patients meeting income criteria, and starting in 2025, a direct-pay option for Wegovy at $499/month for cash-pay patients via NovoCare Pharmacy. The direct-pay channel was Novo's response to compounded competition.

Off-label use refers to prescribing an FDA-approved medication for a use not explicitly stated on the approved labeling. This is legal under US law and is widely practiced — particularly common in oncology, pediatrics, and obesity medicine. For GLP-1s, common off-label uses include Ozempic or Mounjaro prescribed for weight loss (only Wegovy and Zepbound have weight-management labels), and any GLP-1 prescribed for PCOS, NAFLD, or post-bariatric weight regain. Off-label prescribing is acceptable when supported by evidence and patient-specific justification, but insurance coverage for off-label use is typically denied.

Pancreatitis is inflammation of the pancreas presenting with severe epigastric pain, often radiating to the back, with nausea and vomiting. Acute pancreatitis has been reported in patients taking GLP-1 receptor agonists, and the FDA labels include warnings instructing patients to discontinue the medication and seek care for persistent severe abdominal pain. Causal relationship remains debated — large-scale meta-analyses have not consistently demonstrated significantly elevated pancreatitis risk above background, though signals exist. History of pancreatitis is a relative caution; gallstone disease is a related risk factor.

Pharmacy benefit managers (PBMs) administer prescription drug benefits on behalf of insurers, self-funded employers, Medicare Part D plans, and Medicaid programs. PBMs negotiate rebates with manufacturers, set formularies, contract pharmacy networks, and process claims. The three largest PBMs — CVS Caremark (owned by CVS Health/Aetna), Express Scripts (owned by Cigna/Evernorth), and OptumRx (owned by UnitedHealth Group) — collectively process roughly 80% of US prescriptions. PBM rebate structures and formulary decisions significantly shape which GLP-1s a plan covers and at what tier.

Prior authorization (PA) is a utilization management process by which insurers require providers to obtain approval before dispensing covered medications. For GLP-1 RAs, PA typically requires documented diagnosis (T2D HbA1c, BMI plus comorbidity for obesity), prior trial of formulary alternatives (step therapy), labs, and ongoing demonstration of benefit (HbA1c reduction or 5%+ weight loss at re-authorization). PA denials can be appealed. Average GLP-1 PA approval rates vary by plan, indication, and documentation quality.

Risk Evaluation and Mitigation Strategy (REMS) is an FDA-required safety strategy for drugs whose serious risks warrant additional measures beyond standard labeling. REMS programs may include medication guides, communication plans, elements to assure safe use (ETASU), and prescriber/dispenser certification. As of 2026, no commercially available GLP-1 RA carries a REMS program, though all carry a boxed warning regarding the risk of thyroid C-cell tumors observed in rodent studies (relevance to humans remains unclear).

Satiety is the post-meal state of feeling full, which suppresses hunger and reduces food intake until the next eating occasion. It is regulated by gut hormones (GLP-1, PYY, CCK, leptin), gastric distension signals via the vagus nerve, and central nervous system processing in the hypothalamus and brainstem. GLP-1 receptor agonists enhance satiety through both peripheral (slowed gastric emptying) and central (direct receptor binding in arcuate nucleus) mechanisms.

Semaglutide is a 31-amino-acid GLP-1 analog modified at positions 8 and 34 and conjugated to a fatty acid chain that binds albumin, giving it a half-life of approximately 165 hours (about one week). It is dosed once weekly subcutaneously (Ozempic up to 2 mg, Wegovy up to 2.4 mg) or once daily orally (Rybelsus up to 14 mg). FDA-approved indications include T2D (Ozempic, Rybelsus), chronic weight management (Wegovy), and reduction of major adverse cardiovascular events in adults with established CVD and overweight/obesity (Wegovy, 2024).

Semaglutide acetate and semaglutide sodium are salt forms of the semaglutide molecule that some compounding pharmacies used during the shortage period. The FDA issued multiple statements (2023-2024) clarifying that these salt forms are NOT the same as the active pharmaceutical ingredient in FDA-approved Ozempic, Wegovy, or Rybelsus, and they have not been demonstrated safe or effective. The FDA warned consumers about adverse events linked to these compounded products, and Novo Nordisk pursued legal action against pharmacies distributing them.

A single-dose vial (SDV) contains one dose of injectable medication, usually preservative-free. In GLP-1 contexts, compounded semaglutide and tirzepatide from 503A and 503B pharmacies are often dispensed in multi-dose vials (MDVs, 30-day supply) that the patient draws into an insulin syringe. This requires more user dexterity than an autoinjector. Brand-name Zepbound also became available in single-dose vial form in 2024 at a lower direct-pay price through LillyDirect (the so-called 'vial program' for cash-pay patients).

Step therapy (also called 'fail first') is an insurance utilization management technique requiring patients to first try and fail (or have a contraindication to) less expensive medications before the plan will cover a more expensive option. For weight-loss GLP-1s, step therapy commonly requires a documented trial of phentermine, orlistat, naltrexone-bupropion (Contrave), or Saxenda (liraglutide) before approving Wegovy or Zepbound. Documentation must show inadequate efficacy or intolerance. Step therapy exception requests can sometimes be filed for medical contraindications.

Subcutaneous (SC or SubQ) injection delivers medication into the adipose tissue beneath the dermis using a short, fine needle. SC injection provides slower, more sustained absorption than intravenous or intramuscular routes — ideal for peptide drugs like GLP-1 RAs. Most GLP-1s use pre-filled disposable autoinjectors (Wegovy, Zepbound, Mounjaro pens) or multi-dose pens (Ozempic). Common injection sites are abdomen (avoid 2 inches from navel), front of thigh, or back of upper arm; rotate sites to prevent lipohypertrophy.

Telehealth prescribers are licensed clinicians who evaluate, diagnose, and prescribe via telehealth — typically a synchronous video visit, asynchronous questionnaire review, or both. State scope-of-practice laws govern what NPs and PAs may prescribe independently. For GLP-1s, most major direct-to-consumer platforms (Hims, Ro, Henry Meds, Eden, Mochi, etc.) use independent contractor prescribers licensed in the patient's state. Quality of evaluation, follow-up cadence, and clinician oversight vary widely across platforms.

Tirzepatide is a 39-amino-acid synthetic peptide that activates both the GIP and GLP-1 receptors, providing dual incretin agonism. It has a half-life of about 5 days and is dosed once weekly subcutaneously at 2.5, 5, 7.5, 10, 12.5, or 15 mg. Marketed as Mounjaro for type 2 diabetes (FDA approval May 2022) and Zepbound for chronic weight management (Nov 2023) and moderate-to-severe obstructive sleep apnea in adults with obesity (Dec 2024). In SURPASS-2 it outperformed semaglutide on HbA1c and weight loss.

Titration is the stepwise increase in GLP-1 dose over weeks to months, designed to allow GI tolerance to develop. For Wegovy, the standard schedule is 0.25 mg weekly for 4 weeks, then 0.5, 1.0, 1.7, and 2.4 mg, escalating every 4 weeks (full titration = 16-20 weeks). For Mounjaro/Zepbound, the schedule is 2.5 mg weekly for 4 weeks, then 5, 7.5, 10, 12.5, and 15 mg. Some patients tolerate faster escalation; others need extended pauses at a tolerated dose. Skipping titration steps substantially increases nausea, vomiting, and discontinuation risk.

USP General Chapter <797> is the United States Pharmacopeia's enforceable standard for pharmaceutical compounding of sterile preparations. It sets requirements for cleanrooms (ISO classifications), garbing, hand hygiene, environmental monitoring, personnel competency, beyond-use dating, and labeling. Compliance is required for both 503A and 503B compounders preparing sterile products. A revised version became official in November 2023 with updated air-quality and competency requirements. Failures of <797> compliance have been cited in numerous compounding-related sterility incidents.

Weight regain is the recovery of lost weight after discontinuing weight-loss treatment, a phenomenon seen with surgery, diet, and pharmacotherapy. For GLP-1 RAs, the STEP 4 trial (2021) showed patients who stopped semaglutide after 20 weeks regained about two-thirds of lost weight within 48 weeks. SURMOUNT-4 showed similar patterns after tirzepatide withdrawal. Mechanisms include restoration of appetite drive, return of pre-treatment metabolic adaptations, and behavioral pattern reversion. This finding drives the framing of obesity as a chronic disease requiring chronic therapy, similar to hypertension.

A weight-loss plateau is a sustained period during which weight stops decreasing despite ongoing GLP-1 therapy and stable dose. Clinical trial data show mean weight loss continues for 12-18 months on Wegovy and Zepbound, then stabilizes. Plateaus reflect a new energy balance equilibrium — reduced fat mass means lower resting energy expenditure, and behavioral compensation may also occur. Strategies include dose optimization (if not already at max), reinforcing dietary and exercise behaviors, evaluating sleep and stress, and considering combination therapy. Plateaus do not necessarily mean treatment failure.