GLP-1 and Incretin Medications

Medical Disclaimer: This content is for educational purposes only and does not constitute medical advice, diagnosis, or treatment. Information is based on current medical literature and clinical guidelines but may not apply to your specific situation. Individual responses vary based on personal medical history and concurrent conditions. Always consult qualified healthcare providers for medical decisions. Never delay seeking medical care based on content you’ve read. If experiencing a medical emergency, seek immediate medical attention.

These articles provide education to enhance your healthcare partnership. All treatment decisions should involve your healthcare team. Use this knowledge to have informed discussions, not replace medical care.

In Brief

A class of medications originally developed for type 2 diabetes has changed what obesity treatment can achieve. GLP-1 receptor agonists such as semaglutide, and the dual GIP/GLP-1 agonist tirzepatide, produce average weight loss well beyond earlier drugs — roughly 15% with semaglutide and about 20% with tirzepatide in trials of people without diabetes.¹,⁴ But weight loss and cardiovascular benefit are not the same thing, and the evidence is not identical across agents. Semaglutide has been shown in a large placebo-controlled trial to reduce heart attacks, strokes, and cardiovascular death in people with obesity and existing cardiovascular disease but without diabetes — the first weight medication proven to do so.⁹ Tirzepatide produces greater weight loss, and its cardiovascular evidence is emerging, but the trial designed to test it directly in the obesity population has not yet reported.¹¹,¹²

Two further truths shape how these drugs actually perform. First, average results from tightly run trials are not what everyone experiences: outside the trials, weight loss varies widely and depends heavily on whether a person stays on treatment and reaches an effective dose.¹⁶,¹⁷ Second, obesity behaves as a chronic condition — appetite and weight tend to return when the medication stops.⁸ These drugs also carry real costs, uneven access, common gastrointestinal side effects, and a smaller set of more serious risks. This article explains how they work, what the trials show for each agent and population, how that compares with real-world use, and how to weigh the benefits against the limits honestly — including the fast-growing and thinly evidenced practice of “microdosing,” and the additional risks introduced by compounded and unapproved products, dosing errors, and poorly supervised use — which are separate from, and add to, the intrinsic effects of the molecules themselves.

How These Medications Work

GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) are incretin hormones — signals released by the gut after eating. Article 1 introduced the incretin effect in the context of diabetes; the same biology underlies these drugs. Incretins prompt the pancreas to release insulin in a glucose-dependent way (mainly when blood sugar is elevated), restrain the release of glucagon (a hormone that raises blood sugar), and slow the rate at which the stomach empties. Just as important for weight, they act on appetite centers in the brain, reducing hunger and increasing fullness, so people tend to eat less without deliberately restricting. Because the insulin effect is glucose-dependent, these medications used on their own carry a relatively low risk of hypoglycemia (low blood sugar); that risk rises when they are combined with insulin or insulin-secretagogue medications such as sulfonylureas, which may need to be adjusted and monitored by the treating clinician.

The medications are engineered versions of these signals, modified to last far longer than the natural hormones. A GLP-1 receptor agonist (such as semaglutide or liraglutide) activates the GLP-1 receptor. Tirzepatide is a single molecule that activates both the GIP and GLP-1 receptors, which is why it is called a dual incretin agonist; the greater weight loss seen with it is generally attributed to this dual action, though exactly how the GIP component contributes is still being studied.

The practical consequence is that these are not stimulants or fat-burners. They work primarily by changing appetite and energy intake through the same appetite-regulating biology described in Articles 1 and 4 — which is also why appetite, and often weight, return when the drug is stopped.

The Medications and What They Are Approved For

Several agents share this mechanism but differ in receptor targets, dosing, and approved uses. The table summarizes the main ones; approved indications reflect United States regulatory status and continue to expand.

Two points matter for reading this table. First, the same molecule can carry different brand names, formulations, and indications: semaglutide is Ozempic (diabetes injection), Rybelsus (diabetes tablet), and Wegovy (weight-management injection or tablet), while tirzepatide is Mounjaro for diabetes and Zepbound for weight management and sleep apnea. Second, an approval for weight management is not the same as an approval to reduce cardiovascular events; among the weight-management products, Wegovy carries the cardiovascular indication for people with cardiovascular disease and overweight or obesity, based on the trial described below.⁹,¹⁰

This field is moving quickly: since 2025, an oral semaglutide tablet (Wegovy pill, 25 mg) and a higher-dose semaglutide injection (Wegovy HD, 7.2 mg) have been approved for weight management, and further formulations and next-generation agents are in development.²⁵,²⁶ Indications, formulations, and doses therefore change often; current prescribing information and a clinician are the right sources for what applies to a given person.

A pill is now an option. Oral semaglutide for weight management (the Wegovy pill, 25 mg once daily) became available in the United States in 2026, and its approval also includes cardiovascular risk reduction.²⁵ The active molecule is the same as the injection, but oral delivery is not simply “the injection in a tablet”: peptide absorption from the gut is low, so the tablet must be taken on an empty stomach with specific timing to work. Convenience, adherence, tolerability, cost, and the ability to follow those dosing instructions all influence which formulation is practical for a given person.

What the Trials Show: Weight

The weight-loss results are the reason these drugs drew attention, and they are substantial. The figures below come from randomized trials; the most conservative reading of each — the effect regardless of whether participants stayed on treatment — is used where trials report more than one.

Read together, these show a clear gradient: the incretin agents produce substantially greater average loss than older drugs such as liraglutide. In the one direct head-to-head trial, SURMOUNT-5, tirzepatide produced greater average weight loss than semaglutide 2.4 mg. Higher-dose semaglutide 7.2 mg has since been approved on the basis of separate trials, but it has not been tested against tirzepatide in the same randomized trial, so the two highest doses have not been compared directly. Keep one phrase — average loss — in mind throughout. It is the single most misread number in this field, and the next section explains why.

Trial Results Versus the Real World

Trial averages describe a group under close supervision, with structured dose escalation, free medication, and staff following up. They do not describe every individual, and they do not fully describe routine care. Two kinds of real-world data make the gap concrete.

Among people who stay on treatment, real-world results approach the trials. In a 2025 analysis of United States claims data, patients without diabetes who remained on continuous treatment for a year lost about 14.1% of body weight with semaglutide 2.4 mg and about 16.5% with tirzepatide — close to trial figures.¹⁶

But most of the difference between trials and everyday care comes from what happens when treatment is not continuous. In a separate 2025 cohort of 7,881 adults treated for obesity in ordinary practice, mean weight loss at one year was 8.7% — lower than the trials — and the reason was straightforward: many people stopped early or stayed on low doses.¹⁷ Weight loss tracked closely with persistence: 3.6% with early discontinuation, 6.8% with later discontinuation, and 11.9% among those who continued. Those who continued and reached higher maintenance doses did best, losing 13.7% with semaglutide and 18.0% with tirzepatide.¹⁷

Two lessons follow. First, a reported average of 15% or 20% does not mean most people lose that much; response and persistence vary substantially, some people lose considerably more, some lose much less, and some stop before achieving meaningful benefit. This is one of the most important facts to discuss before starting. Second, staying on treatment and reaching an effective dose are among the major factors separating trial-like results from disappointing ones in routine care.

It also helps to remember that “discontinuation” is not one phenomenon. In routine care people stop for very different reasons — adverse effects, cost, insurance changes, supply problems, pregnancy planning, an inadequate response, or simple preference — and those situations are not clinically equivalent; each may call for a different next step.

That last reason matters, because “what if it isn’t working?” is a common and reasonable question. Not everyone responds adequately, and the right reaction is reassessment rather than indefinite escalation or unsupervised dose experimentation. A clinician can reconsider whether the person has actually reached and tolerated an effective maintenance dose, whether treatment has been interrupted, whether another medication is contributing to weight, and whether continuing the same strategy is justified. A disappointing response should prompt that kind of reassessment, not indefinite dose escalation or unsupervised experimentation.

What the Trials Show: Cardiovascular Outcomes

Weight loss is a means, not the destination. What most matters for the heart is whether a medication reduces actual events — heart attack, stroke, and cardiovascular death — and whether it has been proven to in the population taking it. Here the evidence diverges sharply from the weight-loss picture, and conflating the two is the most common error in coverage of these drugs.

The weight-loss hierarchy and the cardiovascular-outcomes hierarchy are not the same. Tirzepatide currently produces greater average weight loss than semaglutide, but semaglutide has the strongest direct evidence for reducing major cardiovascular events in people with overweight or obesity and established cardiovascular disease without diabetes.⁹ Tirzepatide’s cardiovascular result so far comes from a diabetes population and shows it was as good as — not better than — an active comparator, without a placebo group.¹¹ Its dedicated obesity cardiovascular-outcomes trial has not yet reported.¹²

It also helps to translate SELECT’s result into absolute terms. The reduction from 8.0% to 6.5% is a 1.5-percentage-point drop in the primary outcome over the trial period — about 15 fewer primary cardiovascular events for every 1,000 people treated, in a high-risk group that already had cardiovascular disease.⁹ That absolute benefit should not be assumed to apply to lower-risk people without established cardiovascular disease, in whom the same relative reduction would translate into far fewer events prevented.

Observational studies are also beginning to compare these drugs head-to-head in routine care. A large 2025 analysis using US insurance data and target-trial-emulation methods found that semaglutide and tirzepatide produced broadly similar reductions in cardiovascular events among people at elevated risk, including those with type 2 diabetes and obesity.²⁹ Such real-world analyses are useful, but treatment choice, adherence, insurance coverage, and differences between patients can introduce confounding that randomized trials are designed to minimize. They are best read as supportive and hypothesis-generating, not as substitutes for the dedicated randomized cardiovascular-outcomes trials — which is why they are noted here rather than placed in the table above.

One further distinction matters. Analyses that estimate how much a drug should lower cardiovascular risk, based on the risk-factor improvements it produces, are useful but are not the same as counting real events. A post-hoc analysis of the semaglutide-versus-tirzepatide trial, for instance, projected a greater ten-year cardiovascular risk reduction with tirzepatide — but this was a prediction from a risk model, not observed heart attacks, strokes, or deaths.¹³ Predicted cardiovascular-risk reductions are not the same as proven reductions in cardiovascular events.

Heart-Failure Symptoms in Selected Populations

Beyond general cardiovascular events, two trials tested these drugs in a specific, obesity-related form of heart failure — heart failure with preserved ejection fraction (HFpEF) — where excess weight is a major driver. In people with obesity-related HFpEF and no diabetes, semaglutide improved heart-failure symptoms, physical function, and weight (STEP-HFpEF).¹⁴ Tirzepatide, in a related HFpEF-and-obesity population, reduced a composite of cardiovascular death or worsening heart-failure events — a benefit driven by fewer worsening-heart-failure events — and improved symptoms (SUMMIT).¹⁵ These are meaningful findings, but they apply to defined heart-failure populations and should not be generalized to everyone taking these drugs.

The reach of these medications is also widening beyond weight and general cardiovascular risk. Tirzepatide, for instance, is now approved for moderate-to-severe obstructive sleep apnea in adults with obesity, based on a trial showing improved sleep-apnea severity alongside weight loss,³³ and in 2025 semaglutide (Wegovy) received accelerated FDA approval for metabolic dysfunction–associated steatohepatitis (MASH) with moderate-to-advanced fibrosis; kidney outcomes are also under study.³⁷ The unifying theme is that these are increasingly investigated as treatments for obesity-related disease, not merely as appetite suppressants — but benefit is indication- and population-specific, and improvement in one condition should not be generalized to every disease or every patient. How weight and weight loss interact with specific heart conditions — coronary disease, atrial fibrillation, sleep apnea, and the several types of heart failure — is the subject of Article 9.

Alternative Dosing: Titration, Lower Doses, and “Microdosing” — Ahead of the Evidence?

Public conversation increasingly lumps together three different things that should be kept separate:

1. Clinician-directed slower titration, or pausing the dose increase, because a person cannot tolerate the standard escalation.
2. Remaining at an effective lower approved dose because it is working and tolerated, rather than automatically escalating.
3. True experimental “microdosing” — using doses below the studied therapeutic range, splitting doses, or stretching the interval beyond the studied weekly schedule.

The first is a familiar clinical strategy — slowing escalation to manage side effects. The second may be appropriate for selected patients, depending on the medication, indication, response, tolerability, and which doses are approved for maintenance rather than only for titration. Neither should be automatically conflated with the third. “Microdosing” itself is not a standardized medical term, the popular regimens are used inconsistently, and they have not been evaluated in the large randomized trials that established the approved doses.²⁰

The evidence here is genuinely thin, and it is best presented as a hierarchy. Its strongest form is still weak: pharmacokinetic modeling, supported by small case experience, has explored giving a full dose less often — for example every two weeks instead of weekly. Because these drugs persist in the body for weeks, such modeling predicts that stretching the interval might retain much of the effect.¹⁸,¹⁹ But a model of virtual patients, or a handful of cases, is not an outcomes trial, and the authors themselves note the approach lacks validation and call for randomized studies.¹⁸ True sub-therapeutic microdosing — very small weekly amounts — is weaker still: these regimens have not been shown in robust clinical trials to produce reliable long-term weight loss or health outcomes.²⁰

A pharmacokinetic hypothesis and limited case experience exist; randomized evidence does not; and whether any lower-exposure regimen preserves the cardiovascular benefit shown with the trial-tested doses is entirely untested. Lower exposure may reduce side effects, but that is not the same as established long-term safety or efficacy.

Side Effects and More Serious Risks

Most adverse effects are gastrointestinal and mild to moderate, particularly during dose escalation. For a minority of people, however, gastrointestinal symptoms can be severe or persistent, and occasionally lead to dehydration, kidney injury, emergency evaluation, hospitalization, or stopping the drug.³⁶ The table presents the range with the calibration the evidence supports — distinguishing common from rare, and established from still-being-studied.

Because “common” can hide how different two experiences are — occasional early nausea versus stopping the drug — representative trial figures help. The proportions below are the share of participants who reported each symptom at any point during treatment; most such symptoms were mild to moderate and clustered around dose increases.

Two cautions on reading this. First, reporting a symptom is not the same as stopping treatment: far fewer people discontinue because of gastrointestinal effects. In the pooled semaglutide trials about 4% stopped specifically because of gastrointestinal side effects,³⁵ and in the one head-to-head trial (SURMOUNT-5) gastrointestinal-related discontinuation was lower with tirzepatide (2.7%) than semaglutide (5.6%).⁵ Second, the two columns come from different trials and populations, with different ways of counting symptoms; they show the general texture, not a precise head-to-head comparison.

One point sits outside the table and deserves an update. Early reports had raised concern about mood changes and suicidal thoughts. After a comprehensive review, the FDA concluded that the available studies do not support a causal relationship and, in 2026, requested removal of that warning from GLP-1 labeling, while noting that clinical monitoring continues.²⁴ This is a genuine de-escalation of an earlier concern rather than a dismissal of it.

When Symptoms Should Not Be Dismissed as “Just Side Effects”

Because nausea and abdominal discomfort are common early on, there is a real risk of waving away a symptom that is not routine. A small number of symptoms warrant prompt medical attention rather than watchful waiting. In January 2026, UK regulators (the MHRA) strengthened warnings across this drug class after reports of severe acute pancreatitis, including rare necrotising and fatal cases, and specifically advised urgent evaluation for severe, persistent abdominal pain that may radiate to the back, with or without nausea and vomiting.²⁸ These warnings reflect the seriousness of the reported cases and the need to recognize them quickly; they do not mean pancreatitis is common, and the size of any class-wide increase in risk remains debated across different forms of evidence.²⁰,²⁸

Seek prompt medical care for any of the following while taking these medications:

• Severe, persistent abdominal pain, especially pain that radiates to the back (possible pancreatitis).
• Repeated vomiting, or an inability to keep down fluids.
• Signs of dehydration or a marked drop in urine output.
• Severe abdominal swelling with pain and vomiting, or an inability to pass stool or gas (possible bowel obstruction).
• Right-upper-abdominal pain, fever, or yellowing of the skin or eyes (possible gallbladder problem).
• Sudden painless loss of vision or rapidly worsening eyesight.
• Signs of a severe allergic reaction, such as swelling of the face or throat or difficulty breathing.

None of these is common, and listing them is not a prediction that they will happen. The point is narrower: these particular symptoms should prompt a call or a visit rather than being attributed to expected side effects.

What Rare Case Reports Can — and Cannot — Tell Us

Alongside the trials and large databases, the medical literature includes individual case reports of serious events occurring in people on these medications — for example, severe gastroparesis (profound slowing of the stomach), bowel obstruction, retained stomach contents around anesthesia, and severe or necrotising pancreatitis. These reports are worth understanding correctly, because they are easy to misuse in both directions.

A case report cannot establish how often something happens, and it cannot prove that the medication caused the event; the people described often have other contributing conditions. What case reports do well is different and valuable: they flag unusual patterns that warrant closer study. The anesthesia example shows how this matures into useful guidance. Because these drugs slow stomach emptying, case reports and then larger studies documented retained gastric contents in some patients before sedation despite appropriate fasting — a concern now reflected in the medications’ own labeling.³¹,³⁶ Whether that increased residual content translates into more actual aspiration is genuinely debated: large studies have reached differing conclusions, and absolute aspiration rates are low. Partly for that reason, 2024 multi-society guidance moved away from blanket cessation toward individualized, risk-based management — with most patients able to continue, and extra precautions reserved for higher-risk situations.³² The practical takeaway for a reader is simply to tell any anesthesia or procedure team well in advance that they take one of these medications, and to let that team decide.

Pregnancy and Reproductive Considerations

These medications are not used for weight loss during pregnancy. Anyone who is pregnant, planning a pregnancy, or breastfeeding should discuss timing and alternatives with their clinician, since product-specific guidance differs — including how long before a planned pregnancy a given medication should be stopped.³⁰

One point is specific to tirzepatide: because it slows gastric emptying, it may reduce the absorption and effectiveness of oral hormonal contraceptives, an effect that is largest after the first dose and after each dose increase. The tirzepatide labeling advises using a non-oral contraceptive method, or adding a barrier method, for four weeks after starting and for four weeks after each dose increase; non-oral hormonal methods are not affected. Semaglutide labeling does not carry this specific requirement.³⁰

Dosing Errors and Compounded Products

A reader’s actual risk depends not only on the molecule, but on what product they received, who prescribed it, how it was dispensed, and whether anyone is monitoring them. This is where much avoidable harm has occurred.

FDA-approved semaglutide and tirzepatide are dosed in milligrams at standard concentrations, largely in prefilled pens. Compounded versions — custom-prepared, non-FDA-approved products — are often supplied in multi-dose vials at varying concentrations, with instructions sometimes given in “units” rather than milligrams. The FDA has received reports of overdoses, some requiring hospitalization, when patients or clinicians miscalculated doses while converting between milligrams, milliliters, and “units,” in some cases administering five to twenty times the intended amount.²¹ This is a far more consequential hazard for a real reader than another paragraph about nausea.

The commercial ecosystem around these drugs adds a second layer of risk. The FDA has issued repeated waves of warning letters to telehealth companies — continuing through 2026 — over false or misleading marketing of compounded GLP-1 products, including claims implying the products are FDA-approved, “generic,” or equivalent to the branded drugs.²² Compounded and unapproved products should not be assumed equivalent to FDA-approved ones; they have not undergone the same review for quality, safety, or effectiveness.²⁰,²² None of this makes appropriate, clinician-supervised treatment unsafe — it means the source and supervision of a product matter as much as its name.

When Treatment Stops: Weight Regain

Because these medications work by changing appetite biology, appetite and weight tend to return when they are stopped. In the STEP 1 trial extension, participants regained about two-thirds of their lost weight within a year of stopping semaglutide, and much of the cardiometabolic improvement reversed alongside it.⁸ The maintenance trials tell the same story from the other direction: continuing treatment preserved the loss, while switching to placebo led to regain (STEP 4, SURMOUNT-4).⁶,⁷ This is not a failure of willpower or of the drug; it reflects the body’s defense of its weight, and it is the central reason obesity is increasingly treated as a long-term condition. Why the body defends a higher weight, and what that means for planning, is the subject of Article 8.

Maintenance After Major Weight Loss: An Unanswered Practical Question

Suppose someone reaches their goal — a 15% or 20% reduction. A reasonable next question is: now what? This is precisely where the dose-spacing and microdosing trends arise, and it is where the evidence is thinnest. Several approaches are used in practice: continuing the full therapeutic dose; moving, under clinician direction, to a lower maintenance dose where an approved one exists and the response holds; adjusting the dose for tolerability; stopping the medication and accepting the likelihood of some regain; or experimentally extending the interval between doses. Around any of these, the non-medication foundations — food quality, resistance exercise, sleep, and daily movement — remain important, though they have not been shown to fully substitute for the medication’s effect on appetite.

The honest bottom line is that robust evidence has not identified the optimal maintenance strategy for every responder, and the withdrawal trials are the main reason anyone hesitates to simply stop.⁶,⁷,⁸ This is a decision to make with a clinician rather than by following an online protocol; how to build and sustain such a plan is the subject of Article 11.

Cost and Access

Even where these drugs are appropriate, cost and coverage shape who can actually use them. List prices are high, insurance coverage for weight management is uneven, and interruptions in supply or coverage are common — all of which feed the discontinuation that, as shown above, drives real-world results below trial results.¹⁷,²⁰ The affordability problem is also what fuels the compounded-product market and the interest in lower-dose regimens. These are real pressures, and they are best navigated with a clinician and, where relevant, a pharmacist — not resolved by unsupervised improvisation.

What We Know, What We Suspect, and What We Do Not Know

The GLP-1 conversation is often polarized between “miracle drug” and “dangerous poison.” Neither description captures the evidence. The reality is more specific, and it fits in one table.

How to Think About the Decision

Much of this article can be distilled into a sequence of questions worth carrying into a conversation with a clinician:

• What is the actual goal — weight, a specific health outcome, or both?
• What would count as meaningful success — a defined amount of weight, better blood sugar or sleep, improved function, or a specific cardiovascular benefit in an eligible person — so that treatment has a target rather than an open-ended chase for more weight loss?
• What benefit has actually been proven for someone with this particular risk profile, as opposed to predicted or hoped for?
• How long is treatment likely to continue, given that stopping usually brings weight back?
• What happens if the response is inadequate?
• Which side effects are acceptable, and which symptoms would prompt a call?
• What is the plan after substantial weight is lost — and what is the plan if the medication becomes unaffordable or unavailable?

None of these has a universal answer, and that is the point: the right decision depends on the person, not on the drug’s reputation.

Who These Medications Are For

These medications are tools, and the right question is not whether they “work” but whether they are appropriate for a specific person and goal. Eligibility and appropriateness are not the same thing. Eligibility depends on the specific product, and on factors such as age, body-mass index, weight-related conditions, and the approved indication — the precise thresholds differ by drug and change over time, so current prescribing information and a clinician are the reference. Appropriateness is a further question that a label cannot answer: whether the expected benefit justifies the burden, risks, cost, and likely open-ended duration of treatment for that particular person.

The strongest cardiovascular case exists for a defined group — people with established cardiovascular disease and overweight or obesity, in whom semaglutide has proven benefit.⁹ Extending that proven benefit to a young, otherwise low-risk person seeking to lose ten or twenty pounds is not something the trials support; the appropriate expectation there is weight and risk-factor improvement, not a demonstrated reduction in heart attacks or strokes. Matching the medication, the dose, and the expectation to the individual — and monitoring over time — is a decision for a person and their clinician together, and it is where Article 11 (building a plan) returns.

Clinical Bottom Line

GLP-1 and dual-incretin medications produce the largest average weight loss of any drugs approved for obesity — roughly 15% with semaglutide and about 20% with tirzepatide in trials — but average is not everyone: real-world results depend heavily on staying on treatment and reaching an effective dose.¹,⁴,¹⁶,¹⁷ Weight loss and cardiovascular benefit are not the same claim; to date only semaglutide has been shown to reduce major cardiovascular events, and only in people with established cardiovascular disease and overweight or obesity but without diabetes, while tirzepatide’s dedicated obesity cardiovascular-outcomes trial has not yet reported.⁹,¹¹,¹² Because these drugs act on appetite biology, appetite and weight tend to return when they stop, which is why obesity is treated as a long-term condition and treatment is usually ongoing.⁸ Set against real benefits are common gastrointestinal effects, a smaller set of serious risks, high cost, uneven access, and the added hazards of compounded and unsupervised products. The right question is never whether these drugs “work,” but whether a specific agent, dose, and expectation fit a specific person — a decision for that person and their clinician.

What Comes Next

This article covered the incretin-based medications — the most effective drugs currently approved for weight management. They are not, however, the only medications that matter, and they are not right for everyone. Article 6 turns to the rest of the landscape: the older anti-obesity medications, the drugs prescribed mainly for diabetes, heart failure, or kidney disease that also affect weight, the medications that quietly cause weight gain, and what the history of withdrawn weight-loss drugs teaches about judging a treatment by more than the number on the scale.

Key Terms

Incretin — a gut hormone (such as GLP-1 or GIP) released after eating that helps regulate insulin, glucagon, stomach emptying, and appetite.

GLP-1 receptor agonist — a medication that activates the GLP-1 receptor (for example, semaglutide, liraglutide).

Dual incretin (GIP/GLP-1) agonist — a single molecule that activates both the GIP and GLP-1 receptors (tirzepatide).

Major adverse cardiovascular events (MACE) — a combined measure of serious cardiovascular outcomes, typically cardiovascular death, heart attack, and stroke.

Non-inferior vs superior — “non-inferior” means a treatment was shown to be not meaningfully worse than a comparator; “superior” means it was shown to be better. They are different claims.

Compounded product — a custom-prepared medication that is not FDA-approved and has not been reviewed by the FDA for safety, effectiveness, or quality.

Persistence — staying on a medication over time; a major driver of how much benefit is actually achieved.

References

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7. Aronne LJ, Sattar N, Horn DB, et al; SURMOUNT-4 Investigators. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38–48. https://doi.org/10.1001/jama.2023.24945
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10. US Food and Drug Administration. FDA approves first treatment to reduce risk of serious heart problems specifically in adults with obesity or overweight. March 8, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-reduce-risk-serious-heart-problems-specifically-adults-obesity-or
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