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Review · tirzepatide and the GLP-1 receptor agonists · sources read October 3, 2026

Tirzepatide and the GLP-1 class ​

Tirzepatide has beaten every comparator it has been tested against on both glucose and weight, and its limits are now as well measured as its effects. In type 2 diabetes it lowers HbA1c by about two points; in obesity it takes off a fifth of body weight, half as much again as semaglutide in a direct comparison. The weight returns when the drug is stopped, a quarter of what is lost is lean mass, and its one cardiovascular outcome trial showed it to be no worse than an established GLP-1 drug, not better.

−20.9%
body weight on tirzepatide 15 mg at 72 weeks
SURMOUNT-1 · placebo −3.1%
−2.30
HbA1c points on 15 mg at 40 weeks
SURPASS-2 · semaglutide 1 mg −1.86
0.92
hazard ratio for MACE against dulaglutide
SURPASS-CVOT · 95.3% CI 0.83–1.01
+14.0%
regained in a year after switching to placebo
SURMOUNT-4 · continued drug −5.5%

This review covers tirzepatide in depth and the other GLP-1 based drugs as context. It is built from primary sources: the trial reports, their ClinicalTrials.gov results records and the US prescribing information. Of the 46 papers cited, 13 were read as open full text and the rest as abstracts checked against the registry and the label; the reference list marks which. Every chart is a Holochart example that runs live in your browser. Some redraw a published figure from its reported values; others put results from several trials side by side. None of this is medical advice.

One point of method matters throughout. These trials report two estimands. The treatment-regimen (or treatment-policy) estimand is the effect in everyone randomised, whether or not they stayed on the drug. The efficacy (or trial-product) estimand is the effect had everyone stayed on it, and runs one to three percentage points of body weight larger. Press coverage usually quotes the second. This review uses the first unless it says otherwise.

From one receptor to two ​

GLP-1 is a gut hormone released after meals. It raises insulin secretion when glucose is high, suppresses glucagon, slows gastric emptying and reduces appetite through receptors in the brainstem and hypothalamus. Native GLP-1 lasts minutes; the drug class exists because chemists extended that to a day (liraglutide) and then a week, by attaching a fatty acid that binds albumin (semaglutide) or fusing the peptide to an antibody fragment (dulaglutide).

Tirzepatide adds a second hormone. It is a 39-amino-acid peptide built on the sequence of GIP, the other incretin, modified to activate the GLP-1 receptor as well, with a C20 fatty diacid that gives 99% albumin binding and a half-life of about five days (Coskun 2018; Mounjaro label). It is injected once a week, started at 2.5 mg and raised by 2.5 mg every four weeks to 5, 10 or 15 mg.

The two activities are not equal. In the discovery paper's assays tirzepatide bound the GIP receptor about 30 times more tightly than the GLP-1 receptor, and at the GLP-1 receptor it was some 16 times less potent than semaglutide.

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Mean and SEM, human receptors in HEK293 cells, albumin-free. Circles are binding affinity, diamonds are potency for cAMP production. Source: Coskun 2018, section 3.2.

A weak GLP-1 agonist that outperforms a strong one needs explaining. Willard and colleagues (2020) showed that at the GLP-1 receptor tirzepatide is also a biased agonist: it drives cAMP signalling but recruits little β-arrestin (under 10% of GLP-1's maximum) and internalises the receptor less, which may keep more receptor on the cell surface. Whether GIP receptor agonism itself adds weight loss in humans, or mainly improves tolerability, is still argued; no trial has separated the two components.

Type 2 diabetes: the SURPASS trials ​

Five phase 3 trials tested three doses against placebo, semaglutide 1 mg and two basal insulins, across the range from drug-naive patients to those already on insulin. The result was nearly the same in each: HbA1c fell by about two percentage points from a baseline near 8%, more than with any comparator. Switch the chart to body weight to see the second effect: losses of 5 to 11 kg that rise with dose, against gains on insulin.

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Treatment-regimen estimand at week 40 or 52, as tabulated in section 14 of the Mounjaro label, so all five trials use one analysis. Sources: Rosenstock 2021, Frías 2021, Ludvik 2021, Del Prato 2021, Dahl 2022.

SURPASS-2 is the most informative of the five because its comparator was the strongest: 1,879 patients on metformin, randomised to tirzepatide or semaglutide 1 mg for 40 weeks. All three doses were superior on HbA1c and on weight, with a clear dose response in the differences.

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After Figures 1A and 2A of Frías 2021, redrawn from the values in the paper's Results and Table 2.

Two caveats belong with this figure. Semaglutide was given at 1 mg, not the 2 mg diabetes dose approved later, so the trial compares tirzepatide's full range with a mid-range comparator. And the gains were not free: adverse events led 8.5% to stop tirzepatide 15 mg against 4.1% on semaglutide, although rates of nausea (22.1% and 17.9%) and vomiting were similar.

Obesity: the SURMOUNT trials ​

SURMOUNT-1 established the obesity indication: 2,539 adults without diabetes, mean weight 104.8 kg and BMI 38, treated for 72 weeks. Weight fell 15.0% on 5 mg, 19.5% on 10 mg and 20.9% on 15 mg, against 3.1% on placebo.

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After Figure 1A of Jastreboff 2022. Treatment-regimen estimand with 95% confidence intervals, from the abstract.

Means hide the spread. On 15 mg, 57% of participants lost at least a fifth of their body weight, a range previously associated with bariatric surgery; on placebo 3% did. About one in ten did not reach 5%.

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After Figure 1B of Jastreboff 2022. Proportions from the Zepbound label, Study 1.

The rest of the programme varied the population. Weight loss was smaller in people with type 2 diabetes (SURMOUNT-2), as it is with every drug in the class. It added to, and did not replace, what an intensive lifestyle programme had already achieved (SURMOUNT-3: a further 18.4% after an initial 6.9%). It held up in older, sicker groups with sleep apnoea and heart failure.

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Highest dose or maximum tolerated dose against the comparator; hover a point for the trial's size, duration and estimand. SUMMIT's values are the registry's efficacy estimand. Sources: Jastreboff 2022, Garvey 2023, Wadden 2023, Aronne 2024, Aronne 2025, Malhotra 2024, Packer 2025.

Against semaglutide ​

Comparing SURMOUNT-1 with semaglutide's STEP 1 across trials was never satisfactory. SURMOUNT-5 randomised 751 adults with obesity to the maximum tolerated dose of either drug for 72 weeks. Tirzepatide took off 20.2% of body weight and semaglutide 13.7%, a difference of 6.5 percentage points, with a larger fall in waist circumference and more participants at every threshold.

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Means with 95% CIs from the abstract of Aronne 2025. Threshold proportions are the ClinicalTrials.gov observed-case values (318 per arm) and may differ slightly from the paper's.

The trial was open label and funded by tirzepatide's maker, which matters more for reported symptoms than for weight on a scale. Gastrointestinal events were about as common with either drug; vomiting was reported by 15.0% on tirzepatide and 21.3% on semaglutide.

Stopping ​

The weight loss lasts as long as the treatment does. SURMOUNT-4 gave everyone tirzepatide for 36 weeks, by which point they had lost 20.9%, then randomised them to continue or to switch to placebo. Over the next year those who continued lost a further 5.5% and those switched regained 14.0%. Of those who continued, 89.5% kept at least four fifths of their initial loss, against 16.6%.

Semaglutide behaves the same way. In the STEP 1 extension, participants had regained two thirds of their loss a year after stopping, and in STEP 4 those switched to placebo after a 20-week run-in regained 6.9% while those who continued lost another 7.9%.

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This chart plots only the values the papers report in text: the start, the stopping point and the end. The published figures show smooth per-visit curves between them, which are available only as images and were not traced, so the straight lines here are connectors, not data. Sources: Aronne 2024 (Figure 2), Wilding 2022 (Figure 1).

Longer treatment does not change this. In the three-year extension of SURMOUNT-1, weight loss at 176 weeks was 19.7% on 15 mg, close to the 72-week figure, so the effect neither grows nor fades. Among the 1,032 participants who began with prediabetes, 1.3% on tirzepatide developed type 2 diabetes against 13.3% on placebo (hazard ratio 0.07). Seventeen weeks after stopping, the figures were 2.4% and 13.7%: the protection had begun to erode. Obesity treatment with these drugs is, on current evidence, indefinite.

What is lost ​

A DXA substudy of SURMOUNT-1 measured body composition in 160 participants. On tirzepatide, fat mass fell 33.9% and lean mass 10.9%. Of the weight lost, about 74% was fat and 26% lean, the same split as in the placebo group's much smaller loss, and the same across doses, sexes and age groups.

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Week 72 (SURMOUNT-1) and week 68 (STEP 1). The two substudies are separate trials, and the STEP 1 values come from a conference abstract that gives no placebo figures for these measures. Sources: Look 2025, Wilding 2021b.

The placebo group lost weight in the same proportions, so the drug does not appear to take lean tissue selectively. But a quarter of 20% is a large absolute amount, 5.6 kg on average here, which matters most for older patients. DXA lean mass includes water and organ tissue as well as muscle, and trials with direct measures of muscle and function are still few.

Lipids and blood pressure move in the expected direction. Triglycerides fell by up to 29% and systolic pressure by about 7.4 mmHg on 15 mg.

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Percent change from baseline at week 72, SURMOUNT-1. Source: Zepbound label, Table 3.

Beyond weight ​

Three trials tested whether the weight loss translates into benefit in specific diseases of obesity.

Liver. SYNERGY-NASH was a phase 2 trial in 190 people with biopsy-proven steatohepatitis and moderate or advanced fibrosis. After 52 weeks the disease had resolved in 44 to 62% on tirzepatide and 10% on placebo. Fibrosis improved in about half of treated participants at every dose against 30% on placebo, with wide confidence intervals and no dose response, so the effect on scarring is less certain than the effect on inflammation.

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Source: abstract of Loomba 2024.

Sleep apnoea. In the two SURMOUNT-OSA trials, participants began with about 50 breathing interruptions an hour. Tirzepatide reduced that by 25 to 29, placebo by about 5. This became the first drug indication for obstructive sleep apnoea.

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Treatment-regimen estimand with 95% confidence intervals. Source: Malhotra 2024, Tables 2 and 3.

Heart failure. SUMMIT enrolled 731 people with obesity and heart failure with preserved ejection fraction. Over a median of two years, cardiovascular death or worsening heart failure occurred in 9.9% on tirzepatide and 15.3% on placebo (hazard ratio 0.62 (0.41–0.95)). The benefit came entirely from fewer heart-failure events (0.54 (0.34–0.85)); cardiovascular deaths were few and numerically higher on tirzepatide, 8 against 5. Symptom scores improved by 6.9 points more than on placebo.

Hard outcomes ​

The case that GLP-1 receptor agonists prevent cardiovascular events rests on a decade of placebo-controlled trials in type 2 diabetes, extended to obesity without diabetes by SELECT in 2023 and to kidney disease by FLOW in 2024. Tirzepatide's evidence is of a different kind.

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Primary endpoint of each trial: three-point MACE except where labelled. Hover a square for the population, follow-up and event counts. This is a display of separate trials, not a meta-analysis.

SURPASS-CVOT randomised 13,299 people with type 2 diabetes and cardiovascular disease to tirzepatide or to dulaglutide, a GLP-1 drug with proven benefit, in place of placebo. The hazard ratio for MACE was 0.92 (0.83–1.01): tirzepatide met the test of noninferiority and narrowly missed superiority.

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Primary endpoint from the abstract of Nicholls 2025 (a 95.3% interval); other outcomes from section 14.6 of the Mounjaro label and the trial's open-access secondary report. Only the primary endpoint was controlled for multiplicity.

Read strictly, the trial shows tirzepatide is at least as good as dulaglutide for cardiovascular protection. Death from any cause was lower (0.84 (0.75–0.94)), as was the kidney composite, but these were not part of the formal testing sequence and should be taken as supporting, not confirmatory. There is still no placebo-controlled cardiovascular outcome trial of tirzepatide in obesity without diabetes, the question SELECT answered for semaglutide.

The rest of the class ​

Tirzepatide was the first of several attempts to improve on GLP-1 alone by adding a second or third hormone. The chart ranks each agent's main obesity trial; they are separate trials with different populations and lengths, so the ranking is indicative only.

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Highest dose, treatment-policy estimand, adults without diabetes. Sources: Pi-Sunyer 2015 and the Saxenda label, Wharton 2025, le Roux 2026, Wilding 2021, Knop 2023, Garvey 2025, Jastreboff 2022, Jastreboff 2026. All except the label were read as abstracts.

Three things stand out. Adding amylin (cagrilintide with semaglutide) or GIP (tirzepatide) to GLP-1 gives about 20%, and adding glucagon as well (retatrutide) gives 25%, in a trial published days before this review was written. Survodutide, which adds glucagon without GIP, came in below semaglutide. And the oral small molecule orforglipron trades efficacy for convenience: 11% from a daily tablet.

Safety ​

The common adverse effects are gastrointestinal, dose related and concentrated in the weeks of dose escalation. On tirzepatide 15 mg, 28% reported nausea, 23% diarrhoea and 13% vomiting, and 4.3% stopped treatment because of them, against 0.5% on placebo.

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Pooled placebo-controlled obesity trials from each US label. The pools differ in trials, length and titration, so compare each drug with its own placebo (use the toggle), not with the others. Sources: Saxenda, Wegovy, Zepbound and Foundayo labels.

The rarer risks are less settled, and for several the evidence conflicts:

  • Gallbladder disease. A meta-analysis of 76 randomised trials found a relative risk of 1.37 (95% CI 1.23 to 1.52), higher in weight-loss trials (2.29), about 27 extra events per 10,000 patients a year (He 2022). Rapid weight loss itself causes gallstones.
  • Pancreatitis. Confirmed cases were equally rare on tirzepatide and placebo in the obesity trials (0.2% each), and pooled outcome trials show no excess (odds ratio 1.05, 0.78 to 1.40; Cao 2020). One claims-database study reported a ninefold higher rate than with another weight-loss drug, with an interval from 1.25 to 66 (Sodhi 2023). Labels carry a warning.
  • Thyroid C-cell tumours. All labels carry a boxed warning based on rodent studies. In humans a French case-control study found more thyroid cancer after one to three years of use (hazard ratio 1.58; Bezin 2023); a larger Scandinavian cohort did not (0.93, 0.66 to 1.31; Pasternak 2024).
  • Optic neuropathy (NAION). A single-centre study reported a four- to sevenfold higher rate with semaglutide (Hathaway 2024); national cohorts found a two- to threefold increase, roughly one extra case per 10,000 person-years (Simonsen 2025). The European regulator listed it as a very rare effect of semaglutide in 2025. No estimate specific to tirzepatide was found, and the US labels do not mention it.
  • Aspiration under anaesthesia. Delayed gastric emptying can leave food in the stomach after a normal fast; US labels added a warning in late 2024.
  • Suicidal thoughts. Early case reports were not borne out by cohort studies (for suicide death, hazard ratio 1.25, 0.83 to 1.88, against another diabetes drug class; Ueda 2024) or by the regulators' reviews, and in January 2026 the FDA asked for the warning to be removed from the obesity labels.

What is still unknown ​

  • Whether tirzepatide prevents cardiovascular events in people with obesity but not diabetes.
  • Whether GIP agonism contributes to efficacy, or whether a biased GLP-1 agonist alone would do as well.
  • How to stop. No trial has tested tapering, lower maintenance doses or intermittent treatment against continuous therapy for long-term weight.
  • What the lean mass lost means for strength, fracture and frailty over decades, particularly through cycles of loss and regain.
  • How the newer agents compare directly. Only tirzepatide and semaglutide have been tested head to head.

Methods and limits of this review ​

Sources were gathered on October 3, 2026 from PubMed, PubMed Central and Europe PMC, journal sites where the article is free, ClinicalTrials.gov results records and DailyMed labels. Trials were chosen for being the registration or outcome trial of each agent, which are also the most cited. Where the full text was not open, values come from the abstract and were checked against the registry and the label; where sources disagreed, the difference is recorded in the source notes.

Three limits follow. First, 33 of the 46 papers were not read in full, so secondary results, subgroup analyses and supplementary safety tables from those papers are absent. Second, no values were read off figures, so time courses appear only as reported landmarks. Third, comparisons across trials are descriptive: populations, durations and analysis methods differ, and no pooled estimates were calculated. Results available only as company press releases were left out.

References ​

  1. Coskun 2018. Coskun T, Sloop KW, Loghin C, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol Metab 2018;18:3-14. doi:10.1016/j.molmet.2018.09.009. PMID 30473097. Read as: full text.
  2. Willard 2020. Willard FS, Douros JD, Gabe MB, et al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight 2020;5(17):e140532. doi:10.1172/jci.insight.140532. PMID 32730231. Read as: full text.
  3. Rosenstock 2021. Rosenstock J, Wysham C, Frías JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1). Lancet 2021;398:143-155. doi:10.1016/S0140-6736(21)01324-6. PMID 34186022. Read as: abstract.
  4. Frías 2021. Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2). N Engl J Med 2021;385:503-515. doi:10.1056/NEJMoa2107519. PMID 34170647. Read as: full text.
  5. Ludvik 2021. Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3). Lancet 2021;398:583-598. doi:10.1016/S0140-6736(21)01443-4. PMID 34370970. Read as: abstract.
  6. Del Prato 2021. Del Prato S, Kahn SE, Pavo I, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4). Lancet 2021;398:1811-1824. doi:10.1016/S0140-6736(21)02188-7. PMID 34672967. Read as: abstract.
  7. Dahl 2022. Dahl D, Onishi Y, Norwood P, et al. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes (SURPASS-5). JAMA 2022;327:534-545. doi:10.1001/jama.2022.0078. PMID 35133415. Read as: full text.
  8. Nicholls 2025. Nicholls SJ, Pavo I, Bhatt DL, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes (SURPASS-CVOT). N Engl J Med 2025;393:2409-2420. doi:10.1056/NEJMoa2505928. PMID 41406444. Read as: abstract.
  9. Jastreboff 2022. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med 2022;387:205-216. doi:10.1056/NEJMoa2206038. PMID 35658024. Read as: abstract.
  10. Jastreboff 2025. Jastreboff AM, le Roux CW, Stefanski A, et al. Tirzepatide for obesity treatment and diabetes prevention (SURMOUNT-1, 176 weeks). N Engl J Med 2025;392:958-971. doi:10.1056/NEJMoa2410819. PMID 39536238. Read as: abstract.
  11. Look 2025. Look M, Dunn JP, Kushner RF, et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes Obes Metab 2025;27:2720-2729. doi:10.1111/dom.16275. PMID 39996356. Read as: full text.
  12. Garvey 2023. Garvey WT, Frias JP, Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2). Lancet 2023;402:613-626. doi:10.1016/S0140-6736(23)01200-X. PMID 37385275. Read as: abstract.
  13. Wadden 2023. Wadden TA, Chao AM, Machineni S, et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity (SURMOUNT-3). Nat Med 2023;29:2909-2918. doi:10.1038/s41591-023-02597-w. PMID 37840095. Read as: full text.
  14. Aronne 2024. Aronne LJ, Sattar N, Horn DB, et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity (SURMOUNT-4). JAMA 2024;331:38-48. doi:10.1001/jama.2023.24945. PMID 38078870. Read as: full text.
  15. Aronne 2025. Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). N Engl J Med 2025;393:26-36. doi:10.1056/NEJMoa2416394. PMID 40353578. Read as: abstract.
  16. Malhotra 2024. Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA). N Engl J Med 2024;391:1193-1205. doi:10.1056/NEJMoa2404881. PMID 38912654. Read as: full text.
  17. Packer 2025. Packer M, Zile MR, Kramer CM, et al. Tirzepatide for heart failure with preserved ejection fraction and obesity (SUMMIT). N Engl J Med 2025;392:427-437. doi:10.1056/NEJMoa2410027. PMID 39555826. Read as: abstract.
  18. Loomba 2024. Loomba R, Hartman ML, Lawitz EJ, et al. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis (SYNERGY-NASH). N Engl J Med 2024;391:299-310. doi:10.1056/NEJMoa2401943. PMID 38856224. Read as: abstract.
  19. Pi-Sunyer 2015. Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management (SCALE). N Engl J Med 2015;373:11-22. doi:10.1056/NEJMoa1411892. PMID 26132939. Read as: abstract.
  20. Wilding 2021. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med 2021;384:989-1002. doi:10.1056/NEJMoa2032183. PMID 33567185. Read as: abstract.
  21. Wilding 2022. Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab 2022;24:1553-1564. doi:10.1111/dom.14725. PMID 35441470. Read as: full text.
  22. Wilding 2021b. Wilding J, Batterham R, Calanna S, et al. Impact of semaglutide on body composition in adults with overweight or obesity: exploratory analysis of the STEP 1 study. J Endocr Soc 2021;5(Suppl 1):A16-A17. doi:10.1210/jendso/bvab048.030. Read as: abstract.
  23. Rubino 2021. Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity (STEP 4). JAMA 2021;325:1414-1425. doi:10.1001/jama.2021.3224. PMID 33755728. Read as: abstract.
  24. Knop 2023. Knop FK, Aroda VR, do Vale RD, et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1). Lancet 2023;402:705-719. doi:10.1016/S0140-6736(23)01185-6. PMID 37385278. Read as: abstract.
  25. Wharton 2025. Wharton S, Aronne LJ, Stefanski A, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1). N Engl J Med 2025;393:1796-1806. doi:10.1056/NEJMoa2511774. PMID 40960239. Read as: abstract.
  26. Garvey 2025. Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1). N Engl J Med 2025;393:635-647. doi:10.1056/NEJMoa2502081. PMID 40544433. Read as: abstract.
  27. le Roux 2026. le Roux CW, Wharton S, Startseva E, et al. Survodutide once weekly for the treatment of adults with obesity (SYNCHRONIZE-1). N Engl J Med 2026;395:776-787. doi:10.1056/NEJMoa2600751. PMID 42253238. Read as: abstract.
  28. Jastreboff 2026. Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1). N Engl J Med 2026; published online 29 September. doi:10.1056/NEJMoa2604169. PMID 42814954. Read as: abstract.
  29. Marso 2016a. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER). N Engl J Med 2016;375:311-322. doi:10.1056/NEJMoa1603827. PMID 27295427. Read as: full text.
  30. Marso 2016b. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6). N Engl J Med 2016;375:1834-1844. doi:10.1056/NEJMoa1607141. PMID 27633186. Read as: abstract.
  31. Holman 2017. Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes (EXSCEL). N Engl J Med 2017;377:1228-1239. doi:10.1056/NEJMoa1612917. PMID 28910237. Read as: full text.
  32. Hernandez 2018. Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes). Lancet 2018;392:1519-1529. doi:10.1016/S0140-6736(18)32261-X. PMID 30291013. Read as: abstract.
  33. Gerstein 2019. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND). Lancet 2019;394:121-130. doi:10.1016/S0140-6736(19)31149-3. PMID 31189511. Read as: abstract.
  34. Husain 2019. Husain M, Birkenfeld AL, Donsmark M, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes (PIONEER 6). N Engl J Med 2019;381:841-851. doi:10.1056/NEJMoa1901118. PMID 31185157. Read as: abstract.
  35. Gerstein 2021. Gerstein HC, Sattar N, Rosenstock J, et al. Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes (AMPLITUDE-O). N Engl J Med 2021;385:896-907. doi:10.1056/NEJMoa2108269. PMID 34215025. Read as: abstract.
  36. Lincoff 2023. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). N Engl J Med 2023;389:2221-2232. doi:10.1056/NEJMoa2307563. PMID 37952131. Read as: abstract.
  37. McGuire 2025. McGuire DK, Marx N, Mulvagh SL, et al. Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes (SOUL). N Engl J Med 2025;392:2001-2012. doi:10.1056/NEJMoa2501006. PMID 40162642. Read as: abstract.
  38. Perkovic 2024. Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes (FLOW). N Engl J Med 2024;391:109-121. doi:10.1056/NEJMoa2403347. PMID 38785209. Read as: abstract.
  39. Cao 2020. Cao C, Yang S, Zhou Z. GLP-1 receptor agonists and pancreatic safety concerns in type 2 diabetic patients: data from cardiovascular outcome trials. Endocrine 2020;68:518-525. doi:10.1007/s12020-020-02223-6. PMID 32103407. Read as: abstract.
  40. He 2022. He L, Wang J, Ping F, et al. Association of glucagon-like peptide-1 receptor agonist use with risk of gallbladder and biliary diseases: a systematic review and meta-analysis of randomized clinical trials. JAMA Intern Med 2022;182:513-519. doi:10.1001/jamainternmed.2022.0338. PMID 35344001. Read as: abstract.
  41. Sodhi 2023. Sodhi M, Rezaeianzadeh R, Kezouh A, Etminan M. Risk of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists for weight loss. JAMA 2023;330:1795-1797. doi:10.1001/jama.2023.19574. PMID 37796527. Read as: full text.
  42. Bezin 2023. Bezin J, Gouverneur A, Pénichon M, et al. GLP-1 receptor agonists and the risk of thyroid cancer. Diabetes Care 2023;46:384-390. doi:10.2337/dc22-1148. PMID 36356111. Read as: abstract.
  43. Pasternak 2024. Pasternak B, Wintzell V, Hviid A, et al. Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study. BMJ 2024;385:e078225. doi:10.1136/bmj-2023-078225. PMID 38683947. Read as: full text.
  44. Hathaway 2024. Hathaway JT, Shah MP, Hathaway DB, et al. Risk of nonarteritic anterior ischemic optic neuropathy in patients prescribed semaglutide. JAMA Ophthalmol 2024;142:732-739. doi:10.1001/jamaophthalmol.2024.2296. PMID 38958939. Read as: abstract.
  45. Simonsen 2025. Simonsen E, Lund LC, Ernst MT, et al. Use of semaglutide and risk of non-arteritic anterior ischemic optic neuropathy: a Danish-Norwegian cohort study. Diabetes Obes Metab 2025. doi:10.1111/dom.16316. PMID 40098249. Read as: abstract.
  46. Ueda 2024. Ueda P, Söderling J, Wintzell V, et al. GLP-1 receptor agonist use and risk of suicide death. JAMA Intern Med 2024. doi:10.1001/jamainternmed.2024.4369. PMID 39226030. Read as: abstract.
  47. Zepbound label. Zepbound (tirzepatide) injection: US prescribing information, revised 08/2026. DailyMed set ID 487cd7e7-434c-4925-99fa-aa80b1cc776b. Read as: label.
  48. Mounjaro label. Mounjaro (tirzepatide) injection: US prescribing information, effective 2026-08-27. DailyMed set ID d2d7da5d-ad07-4228-955f-cf7e355c8cc0. Read as: label.
  49. Wegovy label. Wegovy (semaglutide): US prescribing information, revised 06/2026. DailyMed set ID ee06186f-2aa3-4990-a760-757579d8f77b. Read as: label.
  50. Saxenda label. Saxenda (liraglutide) injection: US prescribing information, revised 02/2026. DailyMed set ID 3946d389-0926-4f77-a708-0acb8153b143. Read as: label.
  51. Foundayo label. Foundayo (orforglipron) tablets: US prescribing information. DailyMed set ID 8ac446c5-feba-474f-a103-23facb9b5c62. Read as: label.

Chart sources and data: examples/demos/tirzepatide.

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