Glossary

A category of US pharmacy compounding regulated under section 503A of the Federal Food, Drug, and Cosmetic Act. Permits state-licensed pharmacies to compound drugs for individual patients with a valid prescription, under specific conditions.

A specialized connective tissue responsible for storing energy in the form of triglycerides and functioning as an endocrine organ that secretes hormones and signaling molecules (adipokines) involved in metabolism, inflammation, and insulin sensitivity.

Any unfavorable medical occurrence in a patient receiving a pharmaceutical product, whether or not it is considered related to the treatment. Adverse events are systematically tracked in clinical trials to establish a drug's safety profile.

A 37-amino-acid hormone co-secreted with insulin by pancreatic beta cells. Suppresses appetite, slows gastric emptying, and reduces post-meal glucagon secretion. The mechanistic basis for CagriSema and other amylin analogue therapies.

The complex physiological control of hunger and satiety involving hormonal signals (such as GLP-1, leptin, ghrelin, and insulin), neural circuits in the hypothalamus, and gastrointestinal feedback from nutrient intake.

Insulin-producing cells located in the pancreatic islets of Langerhans that regulate blood glucose levels by secreting insulin in response to rising glucose concentrations.

The proportion of an administered drug that reaches the systemic circulation in an unchanged, pharmacologically active form, expressed as a percentage of the total dose given, which determines the drug's therapeutic effectiveness.

A measure of body weight relative to height, calculated as weight in kilograms divided by height in meters squared (kg/m2), used to classify individuals as underweight, normal weight, overweight, or obese.

The combined probability of developing cardiovascular disease and metabolic disorders such as type 2 diabetes, driven by interconnected risk factors including obesity, dyslipidemia, hypertension, insulin resistance, and chronic inflammation.

A large clinical study designed to determine whether a diabetes or metabolic drug reduces or increases the risk of major cardiovascular events such as heart attack, stroke, or cardiovascular death.

The long-term medical management of obesity using lifestyle interventions, pharmacotherapy, and sometimes surgical approaches to achieve and maintain clinically meaningful weight reduction.

A clinical strategy of gradually increasing medication doses over time to identify the optimal therapeutic dose while minimizing the risk and severity of side effects.

The correlation between the amount of a drug administered and the magnitude of its therapeutic effect, used in clinical trials to identify optimal dosing that maximizes efficacy while maintaining acceptable safety.

A clinical trial design in which neither the participants nor the researchers and clinicians involved in the study know which treatment each participant is receiving, eliminating bias in treatment administration, data collection, and outcome assessment.

An abnormal sensation that may include tingling, numbness, burning, or altered touch perception, typically in the extremities. A safety signal reported in retatrutide's Phase 3 trials, not seen with semaglutide or tirzepatide.

The ability of a drug to produce the desired therapeutic effect under controlled conditions, as measured by predefined endpoints in clinical trials.

The estimated treatment effect under conditions of full adherence — what the drug does when actually taken as prescribed. Contrasts with the treatment-regimen estimand.

A measurable outcome in a clinical trial used to evaluate whether a treatment is effective. Primary endpoints are the main results a trial is designed to assess; secondary endpoints provide additional evidence of benefit.

The total amount of energy the body uses to maintain basic physiological functions, physical activity, and thermogenesis, often measured in metabolic studies to assess the impact of weight-loss therapies.

The regulatory authorization granted by the United States Food and Drug Administration that permits a new pharmaceutical drug to be marketed and sold in the United States, based on demonstrated evidence of safety and efficacy from clinical trials.

Brand name for orforglipron, Eli Lilly's once-daily oral GLP-1 receptor agonist. The first non-peptide oral GLP-1 agonist to receive FDA approval (April 2026), with no food or water timing restrictions.

The rate and process by which ingested food is broken down in the stomach and released into the duodenum (the first part of the small intestine), a key physiological process that influences postprandial glucose levels, nutrient absorption, and feelings of fullness.

Undesirable side effects affecting the digestive system, including nausea, vomiting, diarrhea, and constipation, which are the most commonly reported adverse events with incretin-based therapies.

A 28-amino-acid peptide hormone produced primarily by the stomach that stimulates appetite. Often called the 'hunger hormone'. Rises before meals and falls after eating; chronically suppressed after sleeve gastrectomy.

Glucose-dependent insulinotropic polypeptide, an incretin hormone produced by intestinal K-cells that enhances insulin secretion, influences lipid metabolism, and may play a role in energy balance and fat tissue regulation.

Glucagon-like peptide-1, an incretin hormone produced by intestinal L-cells that stimulates insulin secretion, suppresses glucagon release, slows gastric emptying, and promotes satiety.

A peptide hormone produced by pancreatic alpha cells that raises blood glucose levels, increases energy expenditure, promotes hepatic lipid oxidation, and is one of the three receptor targets of retatrutide.

A G-protein-coupled receptor expressed primarily in the liver that mediates the metabolic effects of glucagon, including stimulation of hepatic glucose production, fatty-acid oxidation, and increased energy expenditure.

The physiological process by which the body maintains blood glucose concentrations within a narrow, stable range through the coordinated action of insulin, glucagon, and other hormones.

The regulation of blood glucose concentrations within a target range over time, typically assessed using measures such as HbA1c, fasting glucose, and postprandial glucose levels.

The time required for the concentration of a drug in the body to decrease by half, which determines dosing frequency. Retatrutide has a half-life of approximately 6 days, enabling once-weekly administration.

Glycated hemoglobin, a blood test that reflects average blood glucose levels over the preceding 2-3 months, used as the primary measure of glycemic control in diabetes management and clinical trials.

The amount of triglyceride stored within liver cells, often measured by imaging techniques such as MRI-PDFF, which serves as an important marker of metabolic liver disease and insulin resistance.

The accumulation of excess fat (triglycerides) in liver cells, commonly associated with obesity and insulin resistance, which can progress to steatohepatitis (MASH/NASH), fibrosis, and cirrhosis.

A protein located on or within cells that binds specific signaling molecules such as hormones, triggering intracellular pathways that regulate physiological responses.

A class of gut-derived hormones, primarily GLP-1 and GIP, that are released after eating and stimulate insulin secretion in a glucose-dependent manner, forming the basis for a major class of diabetes and obesity medications.

The phenomenon whereby oral glucose ingestion stimulates a greater insulin response than intravenous glucose due to the release of incretin hormones such as GLP-1 and GIP from the gastrointestinal tract.

A pathological condition in which cells in the muscles, liver, and adipose tissue fail to respond effectively to insulin, impairing glucose uptake from the bloodstream and forcing the pancreas to produce increasingly higher levels of insulin to maintain normal blood sugar levels.

The release of insulin from pancreatic beta cells in response to elevated blood glucose or hormonal signals, a central mechanism targeted by incretin-based therapies.

The degree to which cells in muscle, liver, and adipose tissue respond effectively to insulin's signal to take up glucose from the bloodstream, with higher sensitivity indicating more efficient glucose disposal.

All body mass that is not fat, including muscle, organs, bone, connective tissue, and total body water. Often measured by DXA scan in clinical trials. Preserving lean mass during rapid weight loss is a critical safety endpoint.

An adipocyte-derived hormone that signals long-term energy stores to the brain. Falls during weight loss, contributing to increased appetite and reduced energy expenditure — a key driver of weight regain.

The metabolic process by which fatty acids are broken down within mitochondria to produce energy, often increased by glucagon receptor activation and associated with reductions in liver fat.

A long-term treatment strategy in which medication is continued at a sustained or reduced dose after the initial treatment phase to preserve therapeutic gains and prevent disease recurrence or relapse.

Physiological changes that occur during weight loss in which the body reduces energy expenditure and increases hunger signals, often contributing to weight regain after diet-based interventions.

A cluster of interconnected metabolic abnormalities — including elevated blood pressure, high blood sugar, excess abdominal body fat, and abnormal cholesterol or triglyceride levels — that together significantly increase the risk of cardiovascular disease, type 2 diabetes, and stroke.

A pharmacological agent designed to activate multiple hormone receptors simultaneously to produce synergistic metabolic effects, such as enhanced insulin secretion, appetite suppression, and increased energy expenditure.

An advanced stage of fatty liver disease characterized by inflammation and liver cell damage that can progress to fibrosis and cirrhosis.

A chronic, complex medical condition defined by a body mass index (BMI) of 30 kg/m2 or greater, characterized by excess accumulation of body fat that impairs health and increases the risk of numerous comorbidities including type 2 diabetes, cardiovascular disease, and certain cancers.

The use of medications to treat obesity by modifying appetite regulation, energy expenditure, or metabolic processes, typically prescribed alongside lifestyle interventions.

A class of medications composed of short chains of amino acids designed to mimic or modify natural hormonal signaling pathways.

The study of how a drug is absorbed, distributed, metabolized, and excreted by the body over time (often abbreviated as ADME), which determines dosing strategies and drug behavior in patients.

The first stage of clinical testing in humans, primarily designed to evaluate the safety, tolerability, and pharmacokinetics of a new drug, typically in a small number of healthy volunteers or patients.

The second stage of clinical testing, designed to evaluate a drug's efficacy, optimal dosing, and safety in a larger group of patients with the target condition, typically enrolling hundreds of participants.

Large-scale pivotal clinical trials designed to confirm a drug's efficacy and safety in thousands of patients, providing the definitive evidence required for regulatory approval by agencies such as the FDA.

An inactive substance or treatment designed to resemble the active drug being studied, used as a control in clinical trials to isolate the true pharmacological effects of the investigational agent.

Blood glucose levels measured after eating, commonly used to evaluate how effectively a treatment controls glucose spikes following meals.

The gold standard clinical study design in which participants are randomly assigned to receive either the investigational treatment or a control (such as placebo), enabling researchers to establish causal relationships between the intervention and observed outcomes.

A substance that binds to a specific receptor and activates it, mimicking the action of the body's natural signaling molecules to produce a biological response.

A thyroid hormone receptor beta agonist developed by Madrigal Pharmaceuticals. The first FDA-approved therapy for metabolic dysfunction-associated steatohepatitis (MASH), receiving accelerated approval in March 2024.

A bariatric surgical procedure that creates a small stomach pouch and connects it directly to a more distal segment of the small intestine, bypassing the rest of the stomach and the upper small intestine. Produces 25-35% total body weight loss on average at 1-2 years.

Age-related or weight-loss-related loss of skeletal muscle mass and strength. A clinical concern with high-magnitude weight loss therapy, particularly in older adults.

The physiological and psychological sensation of fullness and satisfaction that occurs during and after eating, which suppresses further food intake and is regulated by hormonal signals from the gut, adipose tissue, and central nervous system.

A bariatric surgical procedure that removes approximately 75-80% of the stomach, leaving a banana-shaped 'sleeve' of stomach roughly the size of a thumb. Produces 20-25% total body weight loss on average at 1-2 years.

A modern clinical term describing liver fat accumulation associated with metabolic dysfunction, replacing the older term non-alcoholic fatty liver disease (NAFLD).

A method of drug administration involving injection into the subcutaneous tissue, the fatty layer located between the skin and the underlying muscle, allowing for slow and sustained absorption into the bloodstream.

Eli Lilly's Phase 3 clinical development program for retatrutide in metabolic dysfunction-associated steatohepatitis (MASH) and related liver outcomes.

Diffuse hair shedding caused by a stressor that pushes a larger-than-normal fraction of scalp hair follicles into the resting (telogen) phase. Commonly reported after rapid weight loss, including with GLP-1-class therapies.

The production of heat by metabolic processes, particularly within brown adipose tissue, which contributes to total energy expenditure.

The degree to which patients can endure a drug's adverse effects, assessed by the rate and severity of side effects and the proportion of patients who discontinue treatment due to adverse events.

Eli Lilly's Phase 3 clinical development program for retatrutide in type 2 diabetes. Parallel to but separate from the TRIUMPH obesity program.

The estimated treatment effect including the impact of discontinuations and adherence variability — what the drug does at the policy level, regardless of whether participants stayed on it.

A molecule that activates three distinct receptor types simultaneously. In the context of retatrutide, a single peptide that agonizes GIP, GLP-1, and glucagon receptors to produce synergistic metabolic effects.

Eli Lilly's Phase 3 clinical development program for retatrutide in obesity and weight management. Comprises four pivotal trials (TRIUMPH-1 through TRIUMPH-4) plus the TRIUMPH-Outcomes cardiovascular outcomes trial.

A chronic metabolic condition characterized by insulin resistance and relative insulin deficiency, resulting in elevated blood glucose levels that, if uncontrolled, lead to serious complications affecting the cardiovascular system, kidneys, nerves, and eyes.

The partial or complete recovery of lost body weight following cessation of a weight loss intervention, driven by metabolic adaptation, hormonal changes, and the re-emergence of pre-treatment appetite patterns.

Western Ontario and McMaster Universities Osteoarthritis Index — a validated patient-reported questionnaire measuring pain, stiffness, and physical function in osteoarthritis, particularly of the knee and hip.