Claim Checker · The GLP-1 Answer Companionglp1.nexagenlabs.com/claims
Look things up
Claim Checker
Look up a claim and see its grade, its sources and the date it was last reviewed.
Every graded claim in the book, with its grade, what it rests on, and the page it is printed on. The letter answers one question only: how strong is the evidence that this particular statement is true? It is not a measure of how big an effect is, how safe something is, or whether it is right for you.
What the grades mean
| Grade | What the claim rests on | How to treat it |
|---|---|---|
| A | An FDA-approved drug label, or several large randomized trials that agree | Solid. Still ask how it applies to you. |
| B | One large randomized trial, or a pooled analysis of large trials | Strong, but not yet repeated or fully checked. |
| C | Small or early randomized trials, observational studies, expert consensus, or a company describing its own data | Worth discussing. Not settled. |
| D | Mechanism (how something should work), or evidence borrowed from a different condition | An idea, not a result. |
| E | Testimonials, social media, or animal studies only | Treat as unknown. |
The rules behind the letters
- A claim can rise no higher than the best evidence you could read for yourself. A result announced in a press release but not yet published is graded on what has actually been shown.
- Without a comparison group, nothing rises above C. People often feel better after starting anything, and only a comparison shows how much of that is the treatment.
- A company describing its own product stays at C until the data are published in full and others can check them.
- Mechanism on its own never rises above D, however convincing it sounds. Biology is full of good explanations that failed in people.
- Evidence from a different condition stays at D. Evidence from animals alone stays at E.
- The grade belongs to the claim, not to the product. The same substance can hold an A for one statement and an E for another.
- Every grade has a date. When new evidence arrives the grade can move, up or down, and the companion site records the change.
Chapter 2: Why Weight Is Biology, Not Willpower
All 13 sources for this chapter
- Stunkard AJ, Harris JR, Pedersen NL, McClearn GE. The body-mass index of twins who have been reared apart. New England Journal of Medicine 1990;322(21):1483–1487. doi:10.1056/NEJM199005243222102.
- Yazdi FT, Clee SM, Meyre D. Obesity genetics in mouse and human: back and forth, and back again. PeerJ 2015;3:e856. doi:10.7717/peerj.856. PMID 25825681. Summarizes twin, adoption and family studies placing 40 to 70 percent of BMI variation on genetic factors.
- Fryar CD, Afful J, Saif NT. Prevalence of overweight, obesity, and severe obesity among adults age 20 and older: United States, 1960–1962 through August 2021–August 2023. NCHS Health E-Stat 2026 Feb;(111):1–7. doi:10.15620/cdc/174643. Table 1.
- Hall KD, Ayuketah A, Brychta R, et al. Ultra-processed diets cause excess calorie intake and weight gain: an inpatient randomized controlled trial of ad libitum food intake. Cell Metabolism 2019;30(1):67–77. doi:10.1016/j.cmet.2019.05.008.
- Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425–432. doi:10.1038/372425a0. PMID 7984236.
- Zimmet P, Collier GR. Of mice and (wo)men: the obesity (ob) gene, its product, leptin, and obesity. Medical Journal of Australia 1996;164(7):393– 394. Editorial summarizing the leptin injection studies in mice.
- Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J. Long-term persistence of hormonal adaptations to weight loss. New England Journal of Medicine 2011;365(17):1597–1604. doi:10.1056/NEJMoa1105816. ClinicalTrials.gov NCT00870259.
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 12.1 and 14.2 (Study 2, Table 8; Study 5, Table 9).
- Fothergill E, Guo J, Howard L, Kerns JC, Knuth ND, Brychta R, Chen KY, Skarulis MC, Walter M, Walter PJ, Hall KD. Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity 2016;24(8):1612–1619. doi:10.1002/oby.21538.
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Section 14.1 (Study 1, Table 2; Study 3, Table 4; Study 4, Table 6).
- Anderson JW, Konz EC, Frederich RC, Wood CL. Long-term weight-loss maintenance: a meta-analysis of US studies. American Journal of Clinical Nutrition 2001;74(5):579–584. doi:10.1093/ajcn/74.5.579.
- Rubino F, Puhl RM, Cummings DE, et al. Joint international consensus statement for ending stigma of obesity. Nature Medicine 2020;26(4):485– 497. doi:10.1038/s41591-020-0803-x.
- King’s College London. Scientific community pledges to end obesity stigma. News release, 3 March 2020; and University College Dublin, Conway Institute, summary of the four-point Pledge to Eradicate Weight Stigma, 2020.
- C
Genes explain roughly 40 to 70 percent of weight differences
- C
Rising obesity reflects changed surroundings
- A
Hormones from the gut and fat help regulate appetite
- A
Weight returns when GLP-1 treatment stops
- C
Appetite hormones stay changed a year after dieting
- C
The body burns less after large weight loss
- C
Most weight lost through diet alone is regained
- D
The body defends one fixed, precise weight
- A
Diet and exercise alone give modest weight loss
- C
Weight stigma harms health and care
Chapter 3: How GLP-1 Works in Your Gut, Brain and Pancreas
All 7 sources for this chapter
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 5.4, 5.9, 5.10, 6.1 (hypoglycemia; heart rate), 7.1, 12.1, 12.2 and 12.3.
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Sections 5.7, 5.9, 6.1 (hypoglycemia; heart rate), 7.1, 12.1, 12.2 and 12.3.
- Friedrichsen M, Breitschaft A, Tadayon S, Wizert A, Skovgaard D. The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Diabetes, Obesity and Metabolism 2021;23(3):754–762. doi:10.1111/dom.14280. Trial conducted by Novo Nordisk.
- Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). New England Journal of Medicine 2025;393(1):26–36. doi:10.1056/NEJMoa2416394. ClinicalTrials.gov NCT05822830; sponsor Eli Lilly and Company.
- US Food and Drug Administration. SAXENDA (liraglutide) injection: Prescribing Information. Novo Nordisk; revised 02/2026 (Reference ID 5751134). Drugs@FDA. Section 12.2.
- Eli Lilly and Company. FDA approves Lilly’s Foundayo (orforglipron). Press release, 1 April 2026 [company].
- Pharmacy Times. Oral GLP-1 orforglipron is approved for obesity. August 2026. Describes orforglipron as a nonpeptide GLP-1 receptor agonist.
- A
The medicines act on the stomach, brain and pancreas
- A
Stomach slowing is strongest early and fades
- C
Stomach slowing is not the main reason for weight loss
- A
The medicines reduce hunger and calorie intake
- C
Fewer food cravings (“food noise”)
- E
Which brain cells respond
- A
Insulin rises mainly when blood sugar is high
- A
Low blood sugar is more likely with insulin or sulfonylureas
- B
Tirzepatide produced more weight loss than semaglutide
- E
GIP explains the difference
- A
Resting heart rate rises slightly
Chapter 4: Semaglutide, Tirzepatide and the New Pills Compared
All 8 sources for this chapter
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 1, 2.1, 6.1, 7.2, 8.2, 8.3, 8.6, 12.3 and 14.2 (Study 2, Table 7; Study 7, Table 10).
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Sections 1, 2.4, 6.1, 7.2, 8.1, 8.3, 12.3 and 14.1 (Study 1, Table 2).
- US Food and Drug Administration. FOUNDAYO (orforglipron) tablets: Prescribing Information. Eli Lilly and Company; revised 07/2026 (Reference ID 5842935). Drugs@FDA. Sections 1, 2.1, 6.1, 7.1 to 7.3, 8.1, 8.3, 8.6, 12.3, 14 (Trial 1, Table 6) and 16.2.
- US Food and Drug Administration. SAXENDA (liraglutide) injection: Prescribing Information. Novo Nordisk; revised 02/2026 (Reference ID 5751134). Drugs@FDA. Sections 1, 2.1, 5.5, 6.1, 8.1, 12.1, 12.3 and 14.1 (Study 1, Table 4).
- Eli Lilly and Company. Lilly’s tirzepatide delivered up to 22.5% weight loss in adults with obesity or overweight in SURMOUNT-1. Press release, 2022. Reports 22.5 percent for participants who stayed on treatment and 20.9 percent for all randomized participants [company].
- Eli Lilly and Company. FDA approves Lilly’s Foundayo (orforglipron), the only GLP-1 pill for weight loss that can be taken any time of day without food or water restrictions. Press release, 1 April 2026. Reports 12.4 percent for participants who stayed on treatment and 11.1 percent regardless of trial completion [company].
- Novo Nordisk. Wegovy® pill approved in the US as first oral GLP-1 for weight management. Company announcement, 22 December 2025. Reports 16.6 percent mean weight loss “when treatment was adhered to” [company].
- Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). New England
- A
Five products are approved for weight management
- A
Average trial weight loss ranges from about 7 to 21 percent
- A
Trial results cannot be reliably compared across labels
- B
Tirzepatide produced more weight loss than semaglutide
- A
Company headline figures run higher than label figures
- A
Side effects are similar in kind across these medicines
- A
Each pill has its own rules and interactions
- A
Prescribing a diabetes brand for weight is permitted off-label
Chapter 5: What Results to Expect
All 11 sources for this chapter
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 8.6 and 14.2 (Table 8, Studies 2 and 3; Table 9, Study 5; Table 11, Study 7).
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Section 14.1 (Tables 2, 3 and 6).
- US Food and Drug Administration. FOUNDAYO (orforglipron) tablets: Prescribing Information. Eli Lilly and Company; revised 07/2026 (Reference ID 5842935). Drugs@FDA. Section 14 (Tables 6 and 7).
- US Food and Drug Administration. SAXENDA (liraglutide) injection: Prescribing Information. Novo Nordisk; revised 02/2026 (Reference ID 5751134). Drugs@FDA. Sections 2.2 and 14.1 (Table 4).
- Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). New England Journal of Medicine 2025;393(1):26–36. doi:10.1056/NEJMoa2416394.
- American College of Cardiology. SURMOUNT-5: greater loss of weight, waist circumference with tirzepatide than semaglutide. Journal Scan, 10 July 2025. Summarizes the trial’s finding that weight loss was about 6 percent lower in men than in women in both groups.
- Ard J, Lee CJ, Gudzune K, et al. Weight reduction over time in tirzepatide- treated participants by early weight loss response: post hoc analysis in SURMOUNT-1. Diabetes, Obesity and Metabolism 2025;27(9):5064–5071. doi:10.1111/dom.16554. PMID 40677091.
- Kokkinos A, Thethi T, Lee CJ, et al. Tirzepatide efficacy and tolerability according to early weight response: a post hoc analysis of the SURMOUNT-1 and SURMOUNT-2 trials. Diabetes, Obesity and Metabolism 2026. doi:10.1111/dom.71009.
- Horn DB, et al. Time to weight plateau with tirzepatide treatment in the SURMOUNT-1 and SURMOUNT-4 clinical trials. Clinical Obesity 2025. doi:10.1111/cob.12734.
- Garvey WT, Batterham RL, Bhatta M, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine 2022;28(10):2083–2091. doi:10.1038/s41591-022-02026-4.
- Jastreboff AM, le Roux CW, Stefanski A, et al. Tirzepatide for obesity treatment and diabetes prevention. New England Journal of Medicine 2025;392(10):958–971. doi:10.1056/NEJMoa2410819. Funded by Eli Lilly.
- A
Results vary widely; most people lose at least 5 percent
- A
People with type 2 diabetes lose less on average
- A
Higher doses give more weight loss on average
- C
Men may lose somewhat less than women
- C
Most slow starters reach 5 percent later
- B
Weight loss largely holds for two to three years on treatment
- A
Waist size, blood pressure and blood fats improve
Chapter 6: Benefits Beyond Weight: Heart, Kidney, Liver, Sleep and More
All 20 sources for this chapter
- Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). New England Journal of Medicine 2023;389(24):2221–2232. doi:10.1056/NEJMoa2307563.
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 1 and 14.
- US Food and Drug Administration. MOUNJARO (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; 2026 revision including the cardiovascular indication approved 28 August 2026 (NDA 215866). Drugs@FDA. Section 1.
- Eli Lilly and Company. FDA approves Lilly’s Mounjaro (tirzepatide) to reduce cardiovascular risk in adults with type 2 diabetes. Press release, 28 August 2026. Reports SURPASS-CVOT: 13,299 participants; hazard ratio 0.92 (95.3% CI 0.83 to 1.01) versus dulaglutide [company].
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Sections 1 and 14.2 (Studies 5 and 6, Table 9).
- Packer M, et al. Tirzepatide for heart failure with preserved ejection fraction and obesity (SUMMIT). New England Journal of Medicine, published online 16 November 2024. doi:10.1056/NEJMoa2410027. ClinicalTrials.gov NCT04847557; sponsor Eli Lilly and Company.
- ConscienHealth. Lilly withdraws tirzepatide application to FDA for heart failure. 3 May 2025. Quotes Lilly’s chief scientific officer: the FDA indicated an additional confirmatory trial is required.
- Perkovic V, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes (FLOW). New England Journal of Medicine 2024;391:109–121. doi:10.1056/NEJMoa2403347. Funded by Novo Nordisk.
- US Food and Drug Administration. OZEMPIC (semaglutide) injection: Prescribing Information. Novo Nordisk; 2026 revision (Reference ID 5808230). Drugs@FDA. Section 1.
- Novo Nordisk. FDA approves Ozempic® (semaglutide) as the only GLP-1 RA to reduce the risk of worsening kidney disease and cardiovascular death in adults with type 2 diabetes and chronic kidney disease. Announcement, 28 January 2025. Reports a 4.9 percentage-point absolute risk reduction at three years [company].
- Colhoun HM, et al. Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial. Nature Medicine 2024;30:2058– 2066. doi:10.1038/s41591-024-03015-5.
- Sanyal AJ, Newsome PN, Kliers I, et al. Phase 3 trial of semaglutide in metabolic dysfunction–associated steatohepatitis (ESSENCE). New England Journal of Medicine 2025;392:2089–2099. doi:10.1056/NEJMoa2413258.
- Bliddal H, et al. Once-weekly semaglutide in persons with obesity and knee osteoarthritis (STEP 9). New England Journal of Medicine 2024;391:1573– 1583. ClinicalTrials.gov NCT05064735.
- Novo Nordisk Inc. STEP 9 results, published in NEJM, demonstrated semaglutide reduced knee osteoarthritis-related pain in people with obesity. Press release, 30 October 2024. States that semaglutide is not approved in the US for knee osteoarthritis [company].
- Jastreboff AM, le Roux CW, Stefanski A, et al. Tirzepatide for obesity treatment and diabetes prevention. New England Journal of Medicine 2025;392(10):958–971. doi:10.1056/NEJMoa2410819. Funded by Eli Lilly.
- Hendershot CS, Bremmer MP, Paladino MB, et al. Once-weekly semaglutide in adults with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry 2025. doi:10.1001/jamapsychiatry.2024.4789.
- Novo Nordisk A/S. Evoke phase 3 trials did not demonstrate a statistically significant reduction in Alzheimer’s disease progression. Company announcement, 24 November 2025 [company].
- Feldman HH, et al. Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer’s disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials. The Lancet, published online 19 March 2026. doi:10.1016/S0140-6736(26)00459-9. ClinicalTrials.gov NCT04777396 and NCT04777409.
- Klausen MK, Justesen SK, Pedersen JN, et al. Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity. Lancet 2026;407:1687–1698. doi:10.1016/S0140-6736(26)00305-3.
- Schacht JP, Sakai JT, Raymond K, Shelton R, et al. Oral semaglutide for alcohol use disorder. American Journal of Psychiatry 2026. doi:10.1176/appi.ajp.20260003.
- A
Semaglutide lowers heart risk in people with heart disease
- A
Tirzepatide lowers heart risk in high-risk type 2 diabetes
- A
Semaglutide slows kidney disease in type 2 diabetes
- A
Semaglutide improves MASH on biopsy
- A
Tirzepatide improves obstructive sleep apnea
- B
Tirzepatide reduces heart failure events
- B
Semaglutide eases knee arthritis pain
- B
Tirzepatide delays type 2 diabetes
- C
Semaglutide reduces problem drinking
- A
Semaglutide does not slow early Alzheimer’s disease
Chapter 7: Your First 30 Days
All 8 sources for this chapter
- US Food and Drug Administration. FOUNDAYO (orforglipron) tablets: Prescribing Information and Medication Guide. Eli Lilly and Company; revised 07/2026 (Reference ID 5842935). Drugs@FDA. Sections 2.1, 2.3, 5.2, 5.4 to 5.6, 6.1, 7.2, 7.3 and 8.3; Medication Guide.
- US Food and Drug Administration. SAXENDA (liraglutide) injection: Prescribing Information, Medication Guide and Instructions for Use. Novo Nordisk; revised 02/2026 (Reference ID 5751134). Drugs@FDA. Sections 2.1, 2.2, 5.2, 5.6, 5.8, 6.1 and 17; Medication Guide; Instructions for Use.
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 2.1, 2.3, 2.4, 5.5, 5.7, 6.1 and 7.1.
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information and Medication Guide. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Sections 2.3, 2.4, 6.1, 7.2 and 8.3; Medication Guide.
- Healio. Most ‘slow responders’ to tirzepatide achieve 5% or greater weight reduction at 72 weeks. 10 May 2024. Reports Gudzune K, et al., presented at the American Association of Clinical Endocrinology annual meeting, May 2024.
- Friedrichsen M, Breitschaft A, Tadayon S, Wizert A, Skovgaard D. The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Diabetes, Obesity and Metabolism 2021;23(3):754–762. doi:10.1111/dom.14280. Trial conducted by Novo Nordisk.
- Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. Obesity 2025;33(8):1475–1503. doi:10.1002/oby.24336.
- Mehrtash F, Dushay J, Manson JE. I am taking a GLP-1 weight-loss medication: what should I know? JAMA Internal Medicine 2025;185(9):1180. doi:10.1001/jamainternmed.2025.1133.
- A
Stomach side effects cluster during the step-up
- A
Low starting doses are meant to ease side effects
- A
Injection-site reactions are uncommon to occasional
- A
Each medicine has its own missed-dose rule
- A
Dehydration risk is highest when starting and stepping up
- C
Smaller, less fatty meals help in the early weeks
- D
Keeping a simple log helps your prescriber
- E
Appetite changes begin within days
Chapter 8: Nausea, Constipation, Diarrhea, Bloating and Reflux
All 8 sources for this chapter
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 2.2, 5.2, 5.3, 5.5, 5.6, 6.1 (Table 3 and text), 6.2, 7.2 and 12.2.
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information and Medication Guide. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Sections 2.1, 5.2 to 5.5, 6.1 (Table 1 and text), 6.2, 7.2 and 12.2; Medication Guide.
- Wharton S, Calanna S, Davies M, Dicker D, Goldman B, Lingvay I, Mosenzon O, Rubino DM, Thomsen M, Wadden TA, Pedersen SD. Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. Diabetes, Obesity and Metabolism 2022;24(1):94–105. doi:10.1111/dom.14551. Pooled STEP 1–3 (NCT03548935, NCT03552757, NCT03611582) and STEP 4 (NCT03548987); trials funded by Novo Nordisk.
- Rubino DM, Pedersen SD, Connery L, et al. Gastrointestinal tolerability and weight reduction associated with tirzepatide in adults with obesity or overweight with and without type 2 diabetes in the SURMOUNT-1 to -4 trials. Diabetes, Obesity and Metabolism 2025 (published online 9 January 2025). doi:10.1111/dom.16176. Post hoc analysis; funded by Eli Lilly and Company.
- Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. Obesity 2025;33(8):1475–1503. doi:10.1002/oby.24336. Published simultaneously in The American Journal of Clinical Nutrition, American Journal of Lifestyle Medicine and Obesity Pillars.
- Spreckley M, Ruggiero CF, Brown A. Bridging the nutrition guidance gap for GLP-1 receptor agonist therapy assisted weight loss: lessons from bariatric surgery. International Journal of Obesity 2026;50(2):265–267. doi:10.1038/s41366-025-01952-w. Perspective article.
- Mehrtash F, Dushay J, Manson JE. I am taking a GLP-1 weight-loss medication: what should I know? JAMA Internal Medicine 2025;185(9):1180. doi:10.1001/jamainternmed.2025.1133.
- MedlinePlus, US National Library of Medicine. Intestinal obstruction (health topic summary from the National Institute of Diabetes and Digestive and Kidney Diseases). Accessed 23 September 2026.
- A
Gut side effects are common, mostly mild, and cluster around dose increases
- A
The stomach-emptying delay is largest after the first dose, then shrinks
- A
Dehydration from gut symptoms can injure the kidneys
- B
Nausea is not needed for weight loss
- C
Smaller, lower-fat meals, regular eating and fluids ease nausea
- C
Fiber and fluids ease constipation
- D
Eating slowly; drinking between meals
- D
Ginger, peppermint tea, acupressure bands
- D
The brain explanation for nausea
- D
Explanations for “sulfur burps”
- E
Supplements sold to fix “sulfur burps”
Chapter 9: Red Flags: When to Call Your Doctor Now
All 7 sources for this chapter
- US Food and Drug Administration. FOUNDAYO (orforglipron) tablets: Prescribing Information and Medication Guide. Eli Lilly and Company; revised 07/2026 (Reference ID 5842935). Drugs@FDA. Boxed Warning; sections 5.1 to 5.9, 6.1, 13.1 and 17; Medication Guide.
- US Food and Drug Administration. SAXENDA (liraglutide) injection: Prescribing Information and Medication Guide. Novo Nordisk; revised 02/2026 (Reference ID 5751134). Drugs@FDA. Sections 5.1, 5.5 and 6.1; Medication Guide.
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information and Medication Guide. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Boxed Warning; sections 4, 5.1 to 5.10, 6.1 and 17; Medication Guide.
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information and Medication Guide. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Boxed Warning; sections 5.1 to 5.9, 6.1 and 17; Medication Guide.
- World Health Organization. The use of semaglutide medicines and risk of nonarteritic anterior ischemic optic neuropathy (NAION). Medical product alert, 27 June 2025. Reports the European Medicines Agency’s conclusion that NAION is a very rare side effect, potentially affecting up to 1 in 10,000 users.
- Safi MQ, Hussain MD, Chaity NJ. Emerging risk of non-arteritic anterior ischemic optic neuropathy (NAION) with semaglutide: a safety alert for clinicians. Annals of Medicine and Surgery 2026;88(5):3012–3013. doi:10.1097/MS9.0000000000004914. Summarizes the UK MHRA Drug Safety Update of 5 February 2026.
- Healio. FDA asks for removal of suicidal ideation risk from GLP-1 labels following investigation. 14 January 2026. Reports the FDA announcement of 13 January 2026: a meta-analysis of 91 placebo-controlled trials in 107,910 participants and a claims-data study.
- A
Serious side effects are uncommon
- A
Pancreatitis is a rare risk that needs urgent care
- A
Gallbladder problems are more common than on placebo
- A
Dehydration can injure the kidneys
- A
Low blood sugar risk rises with insulin or sulfonylureas
- A
Diabetic eye disease can briefly worsen
- C
NAION is a very rare side effect of semaglutide
- E
Thyroid tumors in people
- A
No increased risk of suicidal thoughts
Chapter 10: Protecting Muscle and Bone
All 8 sources for this chapter
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 6.1 (fractures) and 12.2.
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Section 12.2.
- US Food and Drug Administration. FOUNDAYO (orforglipron) tablets: Prescribing Information. Eli Lilly and Company; revised 07/2026 (Reference ID 5842935). Drugs@FDA. Sections 8.5 and 12.2.
- Wilding JPH, Batterham RL, Calanna S, et al. Impact of semaglutide on body composition in adults with overweight or obesity: exploratory analysis of the STEP 1 study. Journal of the Endocrine Society 2021;5(Suppl 1):A16–A17. doi:10.1210/jendso/bvab048.030. Conference abstract; DXA substudy of 140 participants; several authors employed by Novo Nordisk.
- 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, Obesity and Metabolism 2025. doi:10.1111/dom.16275. PMID 39996356. DXA substudy of 160 participants.
- Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. Obesity 2025;33(8):1475–1503. doi:10.1002/oby.24336. Also published in Obesity Pillars, with later corrections.
- Tinsley GM, Heymsfield SB. Fundamental body composition principles provide context for fat-free and skeletal muscle loss with GLP-1 RA treatments. Journal of the Endocrine Society 2024;8(11):bvae164. doi:10.1210/jendso/bvae164. PMID 39372917.
- Alissou M, Demangeat T, Folope V, et al. Impact of semaglutide on fat mass, lean mass and muscle function in patients with obesity: the SEMALEAN
- A
Weight loss on these medicines includes some lean tissue
- C
Fat falls faster than lean mass, in proportion to weight lost
- C
Lean mass is not the same as muscle
- C
Aim for roughly 80 to 120 grams of protein a day
- D
Strength training limits muscle loss during weight loss
- A
More hip and pelvis fractures on semaglutide in women and people 75 and over
- C
Exercise with a GLP-1 medicine protects bone
- C
Older adults face a higher risk of muscle loss
Chapter 11: What to Eat When You’re Not Hungry
All 3 sources for this chapter
- Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. Obesity 2025;33(8):1475–1503. doi:10.1002/oby.24336.
- US Department of Agriculture, Agricultural Research Service. National Nutrient Database for Standard Reference, Legacy release (SR Legacy), as published in FoodData Central. Values per 100 g scaled to the household measures shown; where USDA lists only a larger measure, the smaller serving is calculated from it. Sample values checked against FoodData Central on 23 September 2026: cooked lentils (FDC 172421), Greek yogurt (FDC 170894) and chia seeds (FDC 170554) matched exactly. USDA’s newer Foundation Foods records can differ slightly for some foods. Foods by USDA number: Greek yogurt 01256; cottage cheese 01015; ricotta 01037; egg 01129; tuna 15121; chicken 05064; salmon 15237; shrimp 15151; tofu 16126; tempeh 16114; edamame 11212; lentils 16070; black beans 16015; chickpeas 16057; nonfat milk 01085; soymilk 16120; mozzarella 01028; cheddar 01009; pumpkin seeds 12014; peanut butter 16398; almonds 12061; chia 12006; raspberries 09302; avocado 09037; pear 09252; apple 09003; oatmeal 08121; sweet potato 11508; prunes 09291; banana 09040; broccoli 11091; whole-wheat bread 18075; flaxseed 12220.
- Mehrtash F, Dushay J, Manson JE. I am taking a GLP-1 weight-loss medication: what should I know? JAMA Internal Medicine 2025;185(9):1180. doi:10.1001/jamainternmed.2025.1133.
- C
What you eat matters more when you eat less
- A
Protein and fiber values in the tables
- C
Fiber and fluids help constipation
- C
Small, plain, low-fat meals help nausea
- D
Eat the protein first on low-appetite days
- C
Smaller portions and staying upright help reflux
- C
Ask before taking supplements
Chapter 12: Alcohol, Supplements and Your Other Medicines
All 9 sources for this chapter
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 1, 2.1, 5.3, 7.1, 7.2 and 12.3.
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Sections 5.4, 7.1, 7.2 and 12.3.
- US Food and Drug Administration. FOUNDAYO (orforglipron) tablets: Prescribing Information. Eli Lilly and Company; revised 07/2026 (Reference ID 5842935). Drugs@FDA. Sections 1, 2.2, 6.1, 7.1 to 7.3, 8.3 and 12.3 (Tables 4 and 5).
- US Food and Drug Administration. SAXENDA (liraglutide) injection: Prescribing Information. Novo Nordisk; revised 02/2026 (Reference ID 5751134). Drugs@FDA. Sections 1 and 7.1.
- US Food and Drug Administration. For healthcare professionals: FDA’s examples of drugs that interact with CYP enzymes and transporter systems. fda.gov, content current as of 29 May 2026. Lists St. John’s wort as a strong CYP3A inducer (effect preparation-dependent) and grapefruit juice as a moderate CYP3A inhibitor (sometimes strong, depending on preparation).
- Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. Obesity 2025;33(8):1475–1503. doi:10.1002/oby.24336.
- Mehrtash F, Dushay J, Manson JE. I am taking a GLP-1 weight-loss medication: what should I know? JAMA Internal Medicine 2025;185(9):1180. doi:10.1001/jamainternmed.2025.1133.
- MedlinePlus Medical Encyclopedia, US National Library of Medicine. Drug- induced low blood sugar (article 000310). Last reviewed 27 October 2024. Lists drinking alcohol and missing meals among causes of low blood sugar in people taking diabetes medicines.
- National Institute of Diabetes and Digestive and Kidney Diseases. Symptoms and causes of pancreatitis. niddk.nih.gov, accessed 23 September 2026. Lists gallstones and heavy alcohol use among the most common causes.
- A
Most tested oral medicines are not meaningfully affected
- A
Narrow-margin medicines such as warfarin need closer watching
- A
The semaglutide tablet raises levothyroxine levels
- A
Pills need a backup method with tirzepatide or orforglipron
- A
Insulin and sulfonylureas may need lowering
- A
Several medicines change orforglipron levels
- C
St. John’s wort may lower orforglipron levels
- C
Alcohol adds to stomach, blood sugar and pancreas risks
Chapter 13: Surgery, Colonoscopy and Anesthesia
All 10 sources for this chapter
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Section 5.10 (pulmonary aspiration during general anesthesia or deep sedation).
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Section 5.9.
- US Food and Drug Administration. FOUNDAYO (orforglipron) tablets: Prescribing Information and Medication Guide. Eli Lilly and Company; revised 07/2026 (Reference ID 5842935). Drugs@FDA. Warnings and Precautions: pulmonary aspiration during general anesthesia or deep sedation.
- US Food and Drug Administration. SAXENDA (liraglutide) injection: Prescribing Information. Novo Nordisk; revised 02/2026 (Reference ID 5751134). Drugs@FDA. Section 5.9.
- Sen S, et al. Glucagon-like peptide-1 receptor agonist use and residual gastric content before anesthesia. JAMA Surgery, published online 6 March 2024. doi:10.1001/jamasurg.2024.0111. Cross-sectional study of 124 adults.
- Glucagon-like peptide-1 receptor agonists in the perioperative period: implications for the anaesthesiologist. Review article, PubMed Central PMC10842663. Summarizes the American Society of Anesthesiologists guidance of June 2023.
- Kindel TL, Wang AY, Wadhwa A, et al.; American Gastroenterological Association, American Society for Metabolic and Bariatric Surgery, American Society of Anesthesiologists, International Society of Perioperative Care of Patients with Obesity, Society of American Gastrointestinal and Endoscopic Surgeons. Multisociety clinical practice guidance for the safe use of glucagonlike peptide-1 receptor agonists in the perioperative period. Published online 29 October 2024; Clinical Gastroenterology and Hepatology 2025;23(12):2083–2085. doi:10.1016/j.cgh.2024.10.003.
- Oprea AD, Ostapenko LJ, Sweitzer B, et al. Perioperative management of patients taking glucagon-like peptide 1 receptor agonists: Society for Perioperative Assessment and Quality Improvement (SPAQI) multidisciplinary consensus statement. British Journal of Anaesthesia 2025;135(1):48–78. doi:10.1016/j.bja.2025.04.001. Co-sponsored and endorsed by the American Association of Clinical Endocrinology.
- Medscape. New rec: GLP-1 users should fast 24 hours before anesthesia. 5 June 2025. Reports the SPAQI recommendations on clear-liquid fasting and the timing of carbohydrate-containing drinks.
- El-Boghdadly K, Dhesi J, Fabb P, et al. Elective peri-operative management of adults taking glucagon-like peptide-1 receptor agonists, glucose-dependent insulinotropic peptide agonists and sodium-glucose cotransporter-2 inhibitors: a multidisciplinary consensus statement. Anaesthesia 2025;80(4):412–424. doi:10.1111/anae.16541.
- A
The medicines carry a warning about aspiration under anesthesia
- C
Food often remains in the stomach despite standard fasting
- A
No one yet knows the best way to lower the risk
- C
Pausing the medicine before procedures
- C
A longer clear-liquid fast lowers the risk
- A
Tell every provider before a procedure
- C
Restart once eating normally
Chapter 14: Hair Loss, “Ozempic Face,” Mood and Other Worries
All 9 sources for this chapter
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Section 6.1, Tables 3 and 4 and text on hair loss, dysgeusia and dysesthesia.
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Section 6.1, Table 1 and text on hair loss, dysgeusia and dysesthesia.
- US Food and Drug Administration. FOUNDAYO (orforglipron) tablets: Prescribing Information. Eli Lilly and Company; revised 07/2026 (Reference ID 5842935). Drugs@FDA. Section 6.1, Table 1 and text on hair loss, dizziness, dysgeusia and dysesthesia.
- US Food and Drug Administration. SAXENDA (liraglutide) injection: Prescribing Information. Novo Nordisk; revised 02/2026 (Reference ID 5751134). Drugs@FDA. Sections 6.1 and 6.2.
- Buontempo MG, et al. Exploring the hair loss risk in glucagon-like peptide-1 agonists: emerging concerns and clinical implications. Journal of the European Academy of Dermatology and Venereology 2025. doi:10.1111/jdv.20512.
- Gupta AK, Teasell EM, Economopoulos V, Mirmirani P. GLP-1 therapies and hair loss: a systematic review of current evidence and implications for counseling. SAGE Journals, 2026. doi:10.1177/00368504261444578.
- American Academy of Dermatology. Do you have hair loss or hair shedding? aad.org/hair-shedding, accessed 23 September 2026.
- Baylor College of Medicine. Can you regrow your hair? Dermatology question- and-answer on hair loss with weight-loss medicines. blogs.bcm.edu, 12 March 2026.
- Daneshgaran G, Shauly O, Gould DJ. “Ozempic face” in plastic surgery: a systematic review of the literature on GLP-1 receptor agonist mediated weight
- A
Hair loss is more common on these medicines, especially in women
- C
The shedding is linked to rapid weight loss and usually recovers
- C
Large weight loss can make the face look hollower
- E
“Ozempic face” is something the medicine does beyond weight loss
- A
Tiredness is more common, mostly early
- A
Taste changes are uncommon
- A
Altered skin sensation is common on 7.2 mg semaglutide
- A
No increased risk of suicidal thoughts
Chapter 15: Plateaus
All 7 sources for this chapter
- Polidori D, Sanghvi A, Seeley RJ, Hall KD. How strongly does appetite counter weight loss? Quantification of the feedback control of human energy intake. Obesity 2016;24(11):2289–2295. doi:10.1002/oby.21653. Analysis of a 52week placebo-controlled trial of canagliflozin in 153 people with type 2 diabetes.
- Horn DB, Kahan S, Batterham RL, et al. Time to weight plateau with tirzepatide treatment in the SURMOUNT-1 and SURMOUNT-4 clinical trials. Clinical Obesity 2025;15(3):e12734. doi:10.1111/cob.12734. PMID 39800653. Post hoc analysis.
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Sections 2.1, 2.2 and 14.1 (Study 4, Tables 6 and 7).
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 2.2, 2.5, 8.6 and 14.2 (Study 5, Table 9; Study 8, Table 12).
- US Food and Drug Administration. FOUNDAYO (orforglipron) tablets: Prescribing Information. Eli Lilly and Company; revised 07/2026 (Reference ID 5842935). Drugs@FDA. Sections 2.1, 2.2, 2.3 and 7.1.
- US Food and Drug Administration. SAXENDA (liraglutide) injection: Prescribing Information. Novo Nordisk; revised 02/2026 (Reference ID 5751134). Drugs@FDA. Section 2.
- Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). New England Journal of Medicine 2025;393(1):26–36. doi:10.1056/NEJMoa2416394. ClinicalTrials.gov NCT05822830; sponsor Eli Lilly and Company.
- D
Appetite rises as weight falls
- C
Most people plateau within about 5 to 8 months
- A
The medicine still works at a plateau
- B
Weight loss holds while treatment continues
- A
Higher doses are an option on several labels
- D
Switching medicines helps at a plateau
- D
Cutting harder is not the answer
Chapter 16: For Seniors
All 7 sources for this chapter
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Sections 5.3, 5.7, 6.1 (hypotension), 8.5 and 14.1.
- US Food and Drug Administration. FOUNDAYO (orforglipron) tablets: Prescribing Information. Eli Lilly and Company; revised 07/2026 (Reference ID 5842935). Drugs@FDA. Sections 5.5, 6.1 (hypotension), 8.5 and 14.
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 5.5, 6.1 (hypotension and syncope; fractures; acute kidney injury), 8.5 and 14.1.
- US Food and Drug Administration. SAXENDA (liraglutide) injection: Prescribing Information. Novo Nordisk; revised 02/2026 (Reference ID 5751134). Drugs@FDA. Section 8.5.
- Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. Obesity 2025;33(8):1475–1503. doi:10.1002/oby.24336.
- Centers for Medicare & Medicaid Services. Medicare GLP-1 Bridge: GLP-1 drugs for $50 a month. What you need to know for July 1, 2026. Fact sheet, CMS Product No. 12234, June 2026. medicare.gov.
- NPR. Some Medicare beneficiaries can now get popular obesity drugs for $50 a month. Updated 1 July 2026. Reports that the Medicare GLP-1 Bridge runs from 1 July 2026 to 31 December 2027.
- A
Weight loss is similar across ages
- A
Few trial participants were over 75
- A
More hip and pelvis fractures on semaglutide at 75 and over
- A
Low blood pressure and fainting are more common on the medicines
- A
Low blood sugar is much more common with a sulfonylurea
- C
Older age raises the risk of muscle loss
- A
Medicare GLP-1 Bridge rules
Chapter 17: For Women
All 9 sources for this chapter
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 6.1 (fractures; hair loss), 8.1, 8.2 and 8.3.
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Sections 7.2, 8.1, 8.2, 8.3 and 12.3.
- US Food and Drug Administration. FOUNDAYO (orforglipron) tablets: Prescribing Information. Eli Lilly and Company; revised 07/2026 (Reference ID 5842935). Drugs@FDA. Sections 7.3, 8.1, 8.2 and 8.3.
- Cesta CE, Rotem R, Bateman BT, et al. Safety of GLP-1 receptor agonists and other second-line antidiabetics in early pregnancy. JAMA Internal Medicine 2024;184(2):144–152. doi:10.1001/jamainternmed.2023.6663. Cohort study of 51,826 pregnancies in women with type 2 diabetes.
- GLP-1 receptor agonist treatment in women with polycystic ovary syndrome: a systematic review and meta-analysis. European Journal of Endocrinology 2026;194(3):S25. doi:10.1093/ejendo/lvag033. Eleven randomized trials; searches to 20 September 2024.
- Effects of GLP1RAs on pregnancy rate and menstrual cyclicity in women with polycystic ovary syndrome: a meta-analysis and systematic review. PubMed Central PMC10631119. Eleven randomized trials, 840 women.
- Hurtado MD, Tama E, Fansa S, et al. Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use. Menopause 2024;31:266–274.
- Castaneda R, Bechenati D, Tama E, et al. The role of menopause hormone therapy in modulating tirzepatide-associated weight loss in postmenopausal women with overweight or obesity: a retrospective cohort study. Lancet Obstetrics, Gynaecology, & Women’s Health 2026; published online 22 January 2026. doi:10.1016/S3050-5038(25)00145-1.
- Mayo Clinic news release on the tirzepatide and hormone therapy study, as reported by ScienceDaily, 23 March 2026: 120 adults treated for at least 12
- A
Labels say to stop when pregnancy is recognized
- A
Semaglutide label: stop at least two months before a planned pregnancy
- C
Early-pregnancy exposure was not linked to more birth defects
- A
The pill needs backup with tirzepatide or orforglipron
- A
Semaglutide tablet and orforglipron not recommended when breastfeeding
- C
GLP-1 medicines help weight in PCOS
- C
Hormone therapy adds to weight loss after menopause
- A
More hip and pelvis fractures in women on semaglutide
Chapter 18: Cost, Coverage, Compounded Drugs and Online Pharmacies
All 9 sources for this chapter
- GoodRx. How much does Zepbound (tirzepatide) cost without insurance? Updated 18 May 2026. Reports a January 2026 list price range of $499 to $1,086 for a 28-day supply.
- NPR. Some Medicare beneficiaries can now get popular obesity drugs for $50 a month. Updated 1 July 2026. Reports typical cash prices of $149 to $699 a month even with discounts, and KFF polling on affordability.
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Section 1.
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Section 1.
- Centers for Medicare & Medicaid Services. Medicare GLP-1 Bridge: GLP-1 drugs for $50 a month. Fact sheet, CMS Product No. 12234, June 2026. medicare.gov.
- US Food and Drug Administration. FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. fda.gov, updated 2025. Tirzepatide shortage resolved 19 December 2024; semaglutide shortage resolved 21 February 2025; timelines for ending enforcement discretion.
- US Food and Drug Administration. FDA’s concerns with unapproved GLP-1 drugs used for weight loss. fda.gov, content current as of 1 September 2026.
- Pharmaceutical Technology. Why the FDA issued 30 warning letters to telehealth sites marketing compounded GLP-1s. 2026.
- Sheppard Mullin. FDA’s focus returns to compounding and telehealth: another wave of warning letters. 18 June 2026. Reports 25 warning letters to telehealth companies in the week of 15 June 2026.
- C
Cash prices vary widely and change often
- C
Coverage depends on the plan and the approved use
- A
The shortages of semaglutide and tirzepatide are over
- A
Compounded versions are not FDA-approved or reviewed
- A
Compounded versions carry dosing, storage and labeling risks
- A
“Research” peptides are illegal for human use
- A
The FDA’s warning signs identify risky sellers
Chapter 19: Stopping and Keeping the Weight Off
All 10 sources for this chapter
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Sections 2.2 and 14.1 (Study 4, Tables 6 and 7).
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 2.2, 8.3 and 14.2 (Study 5, Table 9).
- Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes, Obesity and Metabolism 2022;24(8):1553–1564. doi:10.1111/dom.14725. Funded by Novo Nordisk.
- Weight regain trajectories after discontinuation of semaglutide or tirzepatide: a reconstructed aggregate-data Bayesian longitudinal meta-analysis. Endocrinology, Diabetes & Metabolism 2026;9(5):e70325. doi:10.1002/edm2.70325.
- Horn DB, Linetzky B, Davies MJ, et al. Cardiometabolic parameter change by weight regain on tirzepatide withdrawal in adults with obesity: a post hoc analysis of the SURMOUNT-4 trial. JAMA Internal Medicine 2026;186(2):157–167. doi:10.1001/jamainternmed.2025.6112.
- Aronne LJ, Horn DB, le Roux CW, et al. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAINMAINTAIN trial. Nature Medicine 2026. doi:10.1038/s41591-026-04386-7. Trial reported by Eli Lilly and Company.
- US Food and Drug Administration. FOUNDAYO (orforglipron) tablets: Prescribing Information. Eli Lilly and Company; revised 07/2026 (Reference ID 5842935). Drugs@FDA. Section 1.
- Science Media Centre. Expert reaction to an RCT on using orforglipron for maintenance of body weight reduction after weight loss using injectable tirzepatide or semaglutide. 12 May 2026.
- ClinicalTrials.gov. NCT07783854: A randomized controlled study of dose- tapering regimen of semaglutide for weight-loss maintenance in adults with overweight or obesity. First submitted 19 August 2026; not yet recruiting.
- Jensen SBK, Blond MB, Sandsdal RM, et al. Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebocontrolled trial. eClinicalMedicine 2024;69:102475. doi:10.1016/j.eclinm.2024.102475.
- A
Most people regain much of the weight after stopping
- A
Health improvements fade as weight returns
- B
Switching to orforglipron kept most of the loss for a year
- E
Tapering prevents regain
- C
Exercise during treatment helps after stopping
- D
Plan stopping with your prescriber
Chapter 20: The New Wave
All 13 sources for this chapter
- Novo Nordisk. Wegovy pill approved in the US as first oral GLP-1 for weight management. Company announcement, 22 December 2025 (filed with the US SEC on Form 6-K).
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 1, 2 and 14.
- Eli Lilly and Company. FDA approves Lilly’s Foundayo (orforglipron), the only GLP-1 pill for weight loss that can be taken any time of day without food or water restrictions. Press release, 1 April 2026. Reports 11.1 percent regardless of trial completion [company].
- US Food and Drug Administration. FOUNDAYO (orforglipron) tablets: Prescribing Information. Eli Lilly and Company; revised 07/2026 (Reference ID 5842935). Drugs@FDA. Section 1.
- Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity. New England Journal of Medicine 2025;393:635–647. doi:10.1056/NEJMoa2502081. REDEFINE 1.
- Eli Lilly and Company. Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. Press release, 21 May 2026. TRIUMPH-1 topline results; treatment-regimen estimand figures used here [company].
- HCPLive. Once-monthly obesity drug, MariTide, achieves weight loss up to 16% at 1 year. 16 October 2025. Reports the phase 2 trial of maridebart cafraglutide: 592 participants; 12 to 16 percent weight loss at 52 weeks in obesity without diabetes.
- Eli Lilly and Company. Lilly’s triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial. Press release, 11 December 2025. TRIUMPH-4 topline results [company].
- Novo Nordisk. Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP-1 and amylin analogues for weight management. Press release, 18 December 2025.
- GLPFinders. CagriSema: trial results, FDA approval timeline and what we know. Updated 21 August 2026. Reports CagriSema under FDA review and not approved.
- Novo Nordisk. CagriSema demonstrated 23% weight loss in an open-label head-to-head REDEFINE 4 trial in people with obesity, the primary endpoint was not achieved. Company announcement No 13/2026, 23 February 2026 [company].
- ClinicalTrials.gov. NCT07684235: MARITIME-1-EXTENSION, a phase 3 extension trial of maridebart cafraglutide. Started 23 July 2026; estimated primary completion December 2027.
- US Food and Drug Administration. FDA’s concerns with unapproved GLP-1 drugs used for weight loss. fda.gov, content current as of 1 September 2026.
- A
Semaglutide tablet, semaglutide 7.2 mg and orforglipron are approved
- C
Retatrutide produced large weight loss
- B
CagriSema beat placebo
- C
CagriSema did not match tirzepatide
- C
A monthly injection produced 12–16% loss
- A
Retatrutide and cagrilintide cannot be compounded
- D
Waiting has costs as well as possible gains
Chapter 21: GLP-1 for Addiction, Alzheimer’s and More?
All 12 sources for this chapter
- Feldman HH, et al. Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer’s disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials. Lancet 2026; published online 19 March 2026. doi:10.1016/S0140-6736(26)00459-9.
- Klausen MK, Justesen SK, Pedersen JN, et al. Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial. Lancet 2026;407(10540):1687–1698. doi:10.1016/S0140-6736(26)00305-3. Funders included the Novo Nordisk Foundation.
- Hendershot CS, Bremmer MP, Paladino MB, et al. Once-weekly semaglutide in adults with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry 2025;82:395–405. doi:10.1001/jamapsychiatry.2024.4789.
- Schacht JP, Sakai JT, Raymond K, Shelton R, et al. Oral semaglutide for alcohol use disorder: a randomized clinical trial. American Journal of Psychiatry 2026; published online 29 July 2026. doi:10.1176/appi.ajp.20260003.
- University of Colorado Anschutz Medical Campus. Can oral semaglutide reduce alcohol use? News release, 3 August 2026. Quotes the lead investigator that no new medicines for alcohol use disorder have been approved by the FDA since 2006.
- American Psychiatric Association. New research: oral semaglutide reduced heavy drinking in adults with alcohol use disorder. News release, 29 July 2026. Reports the exploratory cannabis finding in 11 participants.
- Novo Nordisk A/S. Evoke phase 3 trials did not demonstrate a statistically significant reduction in Alzheimer’s disease progression. Company announcement, 24 November 2025 [company].
- NeurologyLive. CTAD presentation lays insights into disappointing phase 3 EVOKE trial of GLP-1 semaglutide in Alzheimer disease. Reports a pooled hazard ratio for progression to dementia of 0.96 (95% CI 0.86 to 1.06).
- Michael J. Fox Foundation for Parkinson’s Research. Exenatide, a GLP-1 drug, shows no impact on Parkinson’s symptoms. 5 February 2025. Summarizes the phase 2 lixisenatide trial (New England Journal of Medicine 2024;390:1176–1185) and the phase 3 exenatide trial.
- Vijiaratnam N, et al. Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson’s disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebocontrolled trial. Lancet 2025;405(10479):627–636. doi:10.1016/S01406736(24)02808-3.
- The Editors of The Lancet. Expression of Concern: Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson’s disease in the UK. Lancet 2026;407(10548):2588. doi:10.1016/S0140-6736(26)01241-9. Published online 22 June 2026.
- The Limbic. Lancet issues ‘Expression of Concern’ on exenatide trial. 2 July 2026. Reports that a regulatory inspection at one trial site identified concerns about trial conduct, oversight and governance.
- D
Brain effects suggest wider uses
- C
Semaglutide reduces heavy drinking
- C
Effects on smoking or cannabis
- A
Semaglutide does not slow early Alzheimer’s disease
- C
GLP-1 medicines slow Parkinson’s disease
- D
What the evidence means for these uses
Chapter 22: “Natural GLP-1”
All 9 sources for this chapter
- Bloomberg Law. Unverified GLP-1-related claims flood food, supplement markets. 13 July 2026. Reports minimal federal oversight and no federal definition of “GLP-1 friendly” or similar phrases.
- SupplySide Supplement Journal. Regulators mostly silent on GLP-1 supplement claims. 15 May 2026. Reports that the FDA had issued one warning letter to a supplement company over GLP-1-related claims, dated 10 December 2024.
- Holst JJ, Deacon CF. Glucagon-like peptide 1 and inhibitors of dipeptidyl peptidase IV in the treatment of type 2 diabetes mellitus. Current Opinion in Pharmacology 2004;4:589–596.
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Section 12.3.
- National Center for Complementary and Integrative Health, US National Institutes of Health. Berberine and weight loss: what you need to know. Last updated November 2023. nccih.nih.gov.
- Elahi Vahed I, Shahir-Roudi E, Nojumi S, et al. The effect of berberine on obesity indices: a systematic review and meta-analysis. International Journal of Obesity 2026;50(1):53–73. doi:10.1038/s41366-025-01943-x.
- Middleton J. Weight loss fad berberine (“nature’s Ozempic”) lacks rigorous evidence, has potential harms. American Family Physician Community Blog, American Academy of Family Physicians, 3 July 2023.
- US Federal Trade Commission. FTC settlement bans marketer behind fat- burner diet pills. Press release, September 2014. States that the FTC’s “gut check” weight-loss claims are always false when made for dietary supplements, over-the-counter drugs, or patches, creams, wraps and similar products worn on the body or rubbed into the skin.
- Perraudeau F, McMurdie P, Bullard J, et al. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Research & Care 2020;8(1):e001319. doi:10.1136/bmjdrc2020-001319. All authors were employees of the manufacturer.
- D
Foods and supplements cannot match the medicines
- C
Berberine lowers blood sugar and weight a little
- E
Berberine is “nature’s Ozempic”
- A
No GLP-1 patch is approved; the FTC calls such weight-loss claims false
- E
“GLP-1 booster” supplements work like the medicines
- C
A probiotic blend improved post-meal blood sugar
Chapter 23: How to Read a GLP-1 Headline
All 13 sources for this chapter
- Biotechnology Innovation Organization (BIO), Informa Pharma Intelligence and QLS Advisors. Clinical Development Success Rates and Contributing Factors 2011–2020. February 2021. Reports a 7.9 percent likelihood of approval from phase 1 and a 28.9 percent phase 2 to phase 3 transition rate.
- Yoon HS, Cho CH, Yun MS, et al. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nature Microbiology 2021;6(5):563–573. doi:10.1038/s41564-021-00880-5.
- Perraudeau F, McMurdie P, Bullard J, et al. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Research & Care 2020;8(1):e001319. doi:10.1136/bmjdrc2020-001319.
- Vijiaratnam N, et al. Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson’s disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebocontrolled trial. Lancet 2025;405(10479):627–636. Subject to an Expression of Concern, June 2026 (chapter 21).
- Novo Nordisk A/S. Evoke phase 3 trials did not demonstrate a statistically significant reduction in Alzheimer’s disease progression. Company announcement, 24 November 2025 [company].
- Feldman HH, et al. Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer’s disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials. Lancet 2026; published online 19 March 2026. doi:10.1016/S0140-6736(26)00459-9.
- Novo Nordisk. CagriSema demonstrated 23% weight loss in an open-label head-to-head REDEFINE 4 trial in people with obesity, the primary endpoint was not achieved. Company announcement No 13/2026, 23 February 2026 [company].
- Novo Nordisk. Wegovy pill approved in the US as first oral GLP-1 for weight management. Company announcement, 22 December 2025. Reports 16.6 percent mean weight loss “when treatment was adhered to” [company].
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Section 14.
- Novo Nordisk Canada. REDEFINE 1 press release, 2025. Reports 22.7 percent weight loss if all patients adhered to treatment and 20.4 percent regardless of adherence [company].
- Eli Lilly and Company. Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. Press release, 21 May 2026. Gives both efficacy-estimand and treatment-regimen-estimand results [company].
- Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). New England Journal of Medicine 2023;389(24):2221–2232. doi:10.1056/NEJMoa2307563.
- Hendershot CS, Bremmer MP, Paladino MB, et al. Once-weekly semaglutide in adults with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry 2025;82:395–405. doi:10.1001/jamapsychiatry.2024.4789.
- C
Most treatments that start human trials are never approved
- C
Only about 3 in 10 pass from phase 2 to phase 3
- A
Figures counting everyone are usually lower
- A
Relative and absolute changes can look very different
- A
Improved markers did not mean clinical benefit in Alzheimer’s
- A
Health-record links did not hold up in a randomized trial
Front matter: How the Evidence Is Graded (Table 0.3)
All 13 sources for this chapter
- US Food and Drug Administration. WEGOVY (semaglutide) injection and tablets: Prescribing Information. Novo Nordisk; revised 03/2026 (Reference ID 5766092). Drugs@FDA. Sections 1, 4, 5.1 to 5.4, 5.10, 7.1, 8.1 to 8.3 and 14.1 (Study 1, Table 5).
- US Food and Drug Administration. ZEPBOUND (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; revised 08/2026 (Reference ID 5863109). Drugs@FDA. Sections 1, 4, 5.1, 5.2, 5.5, 5.7, 5.9, 7.2 and 8.1 to 8.3.
- Eli Lilly and Company. FDA approves Lilly’s Foundayo (orforglipron) for adults with obesity, or overweight with weight-related medical problems. Press release, 1 April 2026 [company].
- Mehrtash F, Dushay J, Manson JE. I am taking a GLP-1 weight-loss medication: what should I know? JAMA Internal Medicine 2025;185(9):1180. doi:10.1001/jamainternmed.2025.1133. Source for the pairing of brand and active-ingredient names.
- US Food and Drug Administration. OZEMPIC (semaglutide) injection: Prescribing Information. Novo Nordisk; 2026 revision (Reference ID 5808230). Drugs@FDA. Section 1.
- US Food and Drug Administration. RYBELSUS and OZEMPIC (semaglutide) tablets: Prescribing Information. Novo Nordisk; 2026 revision (Reference ID 5737308). Drugs@FDA. Section 1.
- US Food and Drug Administration. MOUNJARO (tirzepatide) injection: Prescribing Information. Eli Lilly and Company; 2026 revision including the August 2026 cardiovascular indication (NDA 215866). Drugs@FDA. Section 1.
- Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. Obesity 2025;33(8):1475–1503. doi:10.1002/oby.24336.
- Wharton S, Calanna S, Davies M, et al. Gastrointestinal tolerability of onceweekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. Diabetes, Obesity and Metabolism 2022;24(1):94–105. doi:10.1111/dom.14551.
- Rubino DM, Pedersen SD, Connery L, et al. Gastrointestinal tolerability and weight reduction associated with tirzepatide in adults with obesity or overweight with and without type 2 diabetes in the SURMOUNT-1 to -4 trials. Diabetes, Obesity and Metabolism 2025. doi:10.1111/dom.16176.
- Hendershot CS, Bremmer MP, Paladino MB, et al. Once-weekly semaglutide in adults with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry 2025;82(4):395–405. doi:10.1001/jamapsychiatry.2024.4789. ClinicalTrials.gov NCT05520775.
- Middleton J. Weight loss fad berberine (“nature’s Ozempic”) lacks rigorous evidence, has potential harms. American Family Physician Community Blog, American Academy of Family Physicians, 3 July 2023. Summarizes the berberine glucose trials and a 2018 systematic review rating them low to moderate quality.
- Novo Nordisk Inc. Novo Nordisk’s Ozempic® pill, the only FDA-approved oral peptide GLP-1 medication for adults with type 2 diabetes, soon to be available in the US. Press release, 1 May 2026. States that Ozempic tablets 1.5 mg, 4 mg and 9 mg became available from 4 May 2026, that oral semaglutide was previously sold in the US as Rybelsus in a different formulation, and that the tablets are indicated to improve blood sugar and reduce major cardiovascular events in high-risk adults with type 2 diabetes [company].
- A
In people with heart disease and excess weight, semaglutide lowered the risk of heart attack, stroke or cardiovascular death
- B
The nausea is not what drives the weight loss
- C
Semaglutide may reduce heavy drinking
- D
The nausea comes from appetite signals in the brain
- E
Berberine is “nature’s Ozempic”
Every grade has a date. When new evidence arrives the grade can move, up or down, and this page records the change.