Glossary

US pharmacy compounding under section 503A of the Federal Food, Drug, and Cosmetic Act: state-licensed pharmacies may compound drugs for individual patients with a prescription, under set conditions.

Fat tissue. It stores energy as triglycerides and releases hormones (adipokines) that affect metabolism, inflammation and insulin sensitivity.

Any harmful medical event in someone taking a drug, whether or not the drug caused it. Trials track adverse events to build a drug's safety profile.

A 37-amino-acid hormone released with insulin by beta cells. It curbs appetite, slows stomach emptying and lowers glucagon after meals. CagriSema builds on it.

How the body controls hunger and fullness, through hormones (such as GLP-1, leptin, ghrelin and insulin), brain circuits in the hypothalamus and signals from the gut.

Insulin-making cells in the pancreatic islets of Langerhans. They control blood sugar by releasing insulin when glucose rises.

The share of a drug dose that reaches the bloodstream unchanged and active, given as a percentage of the dose. It shapes how well the drug works.

Weight in kilograms divided by height in meters squared (kg/m2). Used to class people as underweight, normal weight, overweight or obese.

The combined chance of heart disease and metabolic disorders such as type 2 diabetes, driven by obesity, abnormal lipids, high blood pressure, insulin resistance and inflammation.

A large trial that tests whether a diabetes or metabolic drug raises or lowers the risk of major heart events such as heart attack, stroke or cardiovascular death.

Long-term medical treatment of obesity with lifestyle changes, medication and sometimes surgery, to reach and keep a clinically meaningful weight loss.

Raising a drug's dose step by step over time, to reach the best treatment dose while keeping side effects as few and mild as possible.

How a drug's effect changes with its dose. Trials use it to find the dose that gives the most benefit with acceptable safety.

A trial in which neither participants nor researchers know who gets which treatment. This removes bias in how treatment is given, data collected and results judged.

Abnormal sensation such as tingling, numbness, burning or altered touch, usually in the hands and feet. A safety signal in retatrutide's Phase 3 trials, not seen with semaglutide or tirzepatide.

A drug's ability to produce the intended effect under controlled conditions, measured by endpoints set in advance in clinical trials.

The treatment effect estimated as if everyone took the drug as prescribed: what the drug does when actually taken. Compare the treatment-regimen estimand.

A measurable trial outcome used to judge whether a treatment works. The primary endpoint is the main result; secondary endpoints add supporting evidence.

The total energy the body uses for basic functions, physical activity and heat production. Metabolic studies measure it to see how weight-loss drugs act.

Authorization from the US Food and Drug Administration to market and sell a new drug in the United States, based on trial evidence that it is safe and effective.

Brand name for orforglipron, Eli Lilly's once-daily GLP-1 pill. The first non-peptide oral GLP-1 agonist approved by the FDA (April 2026), with no food or water timing rules.

How fast the stomach breaks down food and passes it into the small intestine. It affects blood sugar after meals, nutrient absorption and how full you feel.

Digestive side effects such as nausea, vomiting, diarrhea and constipation. They are the most common adverse events with incretin-based drugs.

A 28-amino-acid hormone made mainly by the stomach that drives appetite, the 'hunger hormone'. It rises before meals, falls after eating and stays low after sleeve gastrectomy.

Glucose-dependent insulinotropic polypeptide: a gut hormone (incretin) from intestinal K-cells that boosts insulin release, affects fat metabolism and may help regulate energy balance.

Glucagon-like peptide-1: a gut hormone (incretin) from intestinal L-cells that boosts insulin, lowers glucagon, slows stomach emptying and increases fullness.

A hormone from pancreatic alpha cells that raises blood sugar, increases energy use and burns liver fat. One of retatrutide's three receptor targets.

A receptor found mainly in the liver that carries out glucagon's effects: raising liver glucose output, burning fat and increasing energy use.

How the body keeps blood sugar in a narrow, stable range, through insulin, glucagon and other hormones working together.

Keeping blood sugar within a target range over time, usually judged by HbA1c, fasting glucose and glucose levels after meals.

The time it takes for the amount of a drug in the body to fall by half, which sets how often it is dosed. Retatrutide's is about 6 days, so it is given once a week.

Glycated hemoglobin: a blood test showing average blood sugar over the past 2-3 months. The main measure of blood sugar control in diabetes care and trials.

The amount of fat (triglyceride) stored in liver cells, often measured by MRI-PDFF. A key marker of metabolic liver disease and insulin resistance.

Excess fat (triglycerides) in liver cells, often linked to obesity and insulin resistance. It can progress to steatohepatitis (MASH/NASH), fibrosis and cirrhosis.

A protein on or inside cells that binds a specific hormone or signal molecule and triggers pathways inside the cell that control its response.

Gut hormones, mainly GLP-1 and GIP, released after eating that boost insulin when glucose is high. The basis for a major class of diabetes and obesity drugs.

Glucose taken by mouth triggers more insulin than the same glucose given into a vein, because the gut releases incretin hormones such as GLP-1 and GIP.

When muscle, liver and fat cells respond poorly to insulin, so glucose leaves the blood less easily and the pancreas must make more and more insulin to keep blood sugar normal.

The release of insulin by pancreatic beta cells in response to rising blood sugar or hormone signals. A central target of incretin-based drugs.

How well muscle, liver and fat cells respond to insulin's signal to take up glucose from the blood. Higher sensitivity means glucose is cleared more efficiently.

All body mass that is not fat: muscle, organs, bone, connective tissue and body water. Trials often measure it by DXA. Keeping it during fast weight loss is a key safety endpoint.

A hormone from fat cells that tells the brain how much energy is stored. It falls during weight loss, raising appetite and lowering energy use, a key driver of weight regain.

Breaking down fatty acids inside mitochondria to make energy. Glucagon receptor activation often increases it, and it is linked to lower liver fat.

Continuing a drug long term, at the same or a lower dose, after the first phase of treatment to keep the gains and prevent relapse.

Changes during weight loss in which the body burns less energy and sends stronger hunger signals. A common cause of weight regain after dieting.

A cluster of linked problems (high blood pressure, high blood sugar, excess belly fat and abnormal cholesterol or triglycerides) that together raise the risk of heart disease, type 2 diabetes and stroke.

A drug designed to activate several hormone receptors at once for combined metabolic effects, such as more insulin release, less appetite and higher energy use.

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

A chronic disease defined by a BMI of 30 kg/m2 or more: excess body fat that harms health and raises the risk of type 2 diabetes, heart disease and some cancers.

Using medicines to treat obesity by changing appetite, energy use or metabolism, usually alongside lifestyle changes.

A medicine made of short chains of amino acids, designed to mimic or change the body's natural hormone signals.

How the body absorbs, distributes, breaks down and removes a drug over time (ADME). It shapes dosing and how a drug behaves in patients.

The first stage of testing a new drug in people. It checks safety, tolerability and pharmacokinetics, usually in a small number of healthy volunteers or patients.

The second stage of testing. It checks a drug's efficacy, best dose and safety in a larger group of patients with the target condition, usually hundreds of people.

Large pivotal trials that confirm a drug's efficacy and safety in thousands of patients and give regulators such as the FDA the definitive evidence for approval.

An inactive substance made to look like the drug being tested. Trials use it as a control to show the drug's true effect.

Blood sugar measured after eating. Used to judge how well a treatment controls blood sugar spikes after meals.

The gold-standard study design: people are randomly assigned to the treatment or a control (such as placebo), so researchers can show the treatment caused the results.

A substance that binds to a specific receptor and switches it on, copying the body's own signaling molecules to produce a biological response.

A thyroid hormone receptor beta agonist from Madrigal Pharmaceuticals. The first FDA-approved drug for MASH, given accelerated approval in March 2024.

Bariatric surgery that makes a small stomach pouch joined to a lower part of the small intestine, bypassing the rest of the stomach. Average weight loss 25-35% at 1-2 years.

Loss of skeletal muscle mass and strength with age or weight loss. A clinical concern with treatments that cause large weight loss, especially in older adults.

The feeling of fullness after eating that holds off further eating. Hormone signals from the gut, fat tissue and brain control it.

Bariatric surgery that removes about 75-80% of the stomach, leaving a thumb-width, banana-shaped 'sleeve'. Average weight loss 20-25% at 1-2 years.

The current term for fat build-up in the liver linked to metabolic problems. It replaces the older name non-alcoholic fatty liver disease (NAFLD).

An injection into the fatty layer between the skin and the muscle, from which the drug is absorbed slowly and steadily into the blood.

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

Widespread hair shedding after a stressor pushes more scalp hair follicles than usual into the resting (telogen) phase. Common after rapid weight loss, including on GLP-1 drugs.

Heat produced by metabolism, especially in brown fat. It adds to the body's total energy use.

How well patients can put up with a drug's side effects, judged by how common and severe they are and how many people stop treatment because of them.

Eli Lilly's Phase 3 program for retatrutide in type 2 diabetes. It runs alongside, but separately from, the TRIUMPH obesity program.

The treatment effect including people who stopped or skipped doses: what starting the drug achieves overall, whether or not participants stayed on it.

A molecule that activates three receptor types at once. Retatrutide is one peptide that activates the GIP, GLP-1 and glucagon receptors for combined metabolic effects.

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

A chronic condition in which insulin resistance and too little insulin raise blood sugar. Uncontrolled, it damages the heart, blood vessels, kidneys, nerves and eyes.

Getting back some or all of the lost weight after a weight-loss treatment stops, driven by metabolic adaptation, hormone changes and the return of old appetite patterns.

Western Ontario and McMaster Universities Osteoarthritis Index: a validated patient questionnaire on pain, stiffness and physical function in knee and hip osteoarthritis.