Semaglutide vs Tirzepatide
Tirzepatide produced more weight loss than semaglutide in a direct trial, 20.2 percent against 13.7 over 72 weeks. That is a genuine head-to-head result and it is worth two caveats: the trial was open-label, and the "47 percent more weight loss" figure in the coverage is relative. The absolute difference is 6.5 percentage points.
- Metabolic and weight loss
- Both FDA approved
- A real head-to-head
Somebody ran this trial properly, and one drug won.
Tirzepatide by 6.5 percentage points. The headline everyone quotes says 47 percent, which is the same gap counted a different way.
| Attribute | Semaglutide | Tirzepatide |
|---|---|---|
| Receptors | One: GLP-1 | Two: GLP-1 and GIP |
| Brands | Ozempic, Wegovy, Rybelsus | Mounjaro, Zepbound |
| Head-to-head result | 13.7 percent [1] | 20.2 percent [1] |
| Reached 30 percent loss | 6.9 percent of people [1] | 19.7 percent of people [1] |
| Cardiovascular outcome trial | 20 percent fewer events against placebo [9] | Non-inferior to another GLP-1 drug [10] |
| Self-pay price, direct | About $349 a month [11] | About $299 to $449 by dose [11] |
| Oral form available | Yes, including an oral Wegovy for weight loss since January 2026 [11] | No |
| Boxed warning | Thyroid C-cell tumours [6] | Thyroid C-cell tumours [6] |
Both figures come from the same 72 week trial in the same population.
Semaglutide
A modified copy of GLP-1, the hormone your gut releases after eating. It slows the stomach, prompts insulin release when blood sugar is high and reduces appetite. In plain terms: the drug that started this, approved for diabetes as Ozempic, for weight as Wegovy, and available as a tablet.
Tirzepatide
A synthetic peptide activating both GLP-1 and GIP receptors. GIP is a second gut hormone that appears to add to the appetite effect and to how the body handles fat and glucose. In plain terms: the same idea with a second lever, approved as Mounjaro and Zepbound.
The result is real. The headline number is not the one you think.
| Measure | Semaglutide | Tirzepatide |
|---|---|---|
| Weight change | 13.7 percent | 20.2 percent |
| Absolute weight lost | 15.0 kg | 22.8 kg |
| Waist circumference | 13.0 cm | 18.4 cm |
| Lost 10 percent or more | 60.5 percent | 81.6 percent |
| Lost 20 percent or more | 27.3 percent | 48.4 percent |
| Lost 30 percent or more | 6.9 percent | 19.7 percent |
The result. SURMOUNT-5 randomised 751 adults with obesity and without diabetes to the maximum tolerated dose of either drug, for 72 weeks. Tirzepatide was superior on the primary endpoint and on all five key secondary endpoints, at p less than 0.001. The result is clean and it settles the question the trial asked. [1]
The number in the headlines is a different one. Almost every report leads with tirzepatide producing 47 percent more weight loss. That figure is real and it is relative, being the gap between 20.2 and 13.7 expressed as a proportion of 13.7. Stated in absolute terms, the difference is 6.5 percentage points. For someone weighing 100 kilograms, the practical difference is roughly 7.8 kilograms across 72 weeks.
The caveat that gets left out is the design. SURMOUNT-5 was open-label. Participants and investigators both knew which drug was being given. [1] In a weight loss trial that matters more than it would elsewhere. A separate detail explains why both figures look low: weight reduction was about 6 percent lower in men than in women for both drugs, and this trial enrolled a higher proportion of men than earlier ones. [1]
Everything that differs
| Attribute | Semaglutide | Tirzepatide |
|---|---|---|
| Also called | Ozempic, Wegovy, Rybelsus | Mounjaro, Zepbound |
| Receptors | GLP-1 | GLP-1 and GIP |
| Dosing | Once weekly injection, or a daily tablet | Once weekly injection |
| Top dose for weight | 2.4 mg | 15 mg |
| Head-to-head weight loss | 13.7 percent [1] | 20.2 percent [1] |
| Absolute weight lost | 15.0 kg [1] | 22.8 kg [1] |
| Reached 30 percent loss | 6.9 percent [1] | 19.7 percent [1] |
| Own pivotal trial | STEP programme | SURMOUNT programme |
| Approved for | Type 2 diabetes and weight management | Type 2 diabetes and weight management |
| Also approved for | Cardiovascular risk reduction in some patients | Obstructive sleep apnoea in obesity |
| Boxed warning | Thyroid C-cell tumours [6] | Thyroid C-cell tumours [6] |
| Most common effects | Gastrointestinal, dose dependent [1] | Gastrointestinal, dose dependent [1] |
| Retail list price | About $1,349 a month [11] | About $1,086 a month [11] |
| Manufacturer self-pay | About $349 a month, or $149 to $299 for the pill [11] | $299 at 2.5 mg, $399 at 5 mg, $449 at 7.5 mg and above [11] |
| With insurance and a savings card | As low as $25 a month [11] | As low as $25 a month [11] |
A 6.5 point difference from an unblinded trial, reported as 47 percent.
Approved as Ozempic
The FDA approves semaglutide for type 2 diabetes, following the SUSTAIN trial programme.
STEP 1 is published
68 weeks, adults with obesity and without diabetes, producing around 15 percent weight loss on 2.4 milligrams weekly. The FDA approves semaglutide as Wegovy for chronic weight management, and the modern obesity drug market begins. [4]
Approved as Mounjaro, and SURMOUNT-1 published
The FDA approves tirzepatide for type 2 diabetes. SURMOUNT-1 appears in the New England Journal of Medicine: 72 weeks, 2,539 adults with obesity and without diabetes. The 15 milligram dose produced 22.5 percent weight loss on one measure and 20.9 percent on another, the difference being how each handles people who stopped treatment. [5]
SELECT reports
17,604 adults with existing cardiovascular disease and obesity or overweight, without diabetes, across 804 sites in 41 countries. Semaglutide reduced major adverse cardiovascular events by 20 percent, hazard ratio 0.80, p less than 0.001.
Two figures need separating. In absolute terms the trial moved the event rate from 8.0 percent to 6.5, a difference of 1.5 percentage points, giving a number needed to treat of 67. The benefit also appeared early, with a 38 percent reduction in the first three months, when average weight loss was still under 5 percent and before participants reached the top dose. [9]
Approved as Zepbound
The FDA approves tirzepatide for chronic weight management. The two drugs are now direct competitors, and every comparison until this point is between separate trials.
The first head-to-head, by press release
Eli Lilly announces topline results from SURMOUNT-5. Tirzepatide 20.2 percent against semaglutide 13.7. [1]
SURMOUNT-5 is published
In the New England Journal of Medicine, and presented at the European Congress on Obesity in Malaga. 751 adults, 72 weeks, open-label, run by Louis Aronne at Weill Cornell. Tirzepatide superior on the primary endpoint and all five key secondary endpoints. [1]
SURPASS-CVOT reports
13,299 adults with type 2 diabetes and established cardiovascular disease, comparing tirzepatide against dulaglutide, another GLP-1 drug with its own cardiovascular approval. Tirzepatide was non-inferior, with a hazard ratio around 0.90 to 0.95, directionally favouring tirzepatide without reaching superiority. [10]
That establishes cardiovascular safety. It is a different claim from demonstrating benefit against placebo.
A post-hoc cardiovascular estimate
An analysis estimates 10-year cardiovascular risk reduction from the SURMOUNT-5 data: 2.4 percentage points for tirzepatide against 1.4 for semaglutide. This used a predicted risk score rather than counted events, it was not a pre-specified endpoint, and six of the eight authors were employees of the trial's sponsor. [2]
The compounded market closes
The FDA declared the tirzepatide shortage resolved in October 2024, and enforcement discretion for large-scale compounding ended in early 2025. In April 2026 the agency proposed removing semaglutide from the 503B bulk drug list, which would end large-scale compounding of that too once finalised. [12]
Millions of people had been obtaining compounded versions during the shortage years. Those were never the approved products, and every trial result on this page belongs to the manufactured ones.
An oral Wegovy launches
Novo Nordisk launches the first oral GLP-1 approved specifically for weight loss, priced at $149 to $299 a month through its direct pharmacy. [11]
Where this leaves them
Both are approved and widely prescribed, and one of them has a head-to-head win behind it.
None of this makes tirzepatide the wrong answer. It won the trial that was run, on every measure the trial looked at. The claim is narrower: a 6.5 point difference from an unblinded study is a different thing from a 47 percent improvement, and only one of those phrasings tells you what to expect.
One gut hormone copied, or two.
Semaglutide
It activates the GLP-1 receptor. GLP-1 is released by your gut after eating, and it slows stomach emptying, triggers insulin release when blood sugar is high, and acts on appetite centres in the brain. A fatty acid modification binds albumin, which is what stretches it to weekly dosing.
Semaglutide has the stronger cardiovascular evidence, because SELECT demonstrated fewer actual events against placebo in a population without diabetes. [9] One detail there complicates the assumption that weight drives the benefit: the effect appeared within three months, when average weight loss was under 5 percent.
It is also the only one of the two that survives oral delivery, with an absorption enhancer. For anyone who will not inject, that is the deciding factor regardless of which produces more weight loss.
Tirzepatide
It adds a second target, the GIP receptor. GIP is another gut hormone, and its role took a long time to become clear. It appears to add to appetite suppression and to improve how the body handles fat and glucose, and it may reduce the nausea that comes with GLP-1 activation, allowing higher effective dosing.
Adding a second receptor produced roughly half again as much weight loss. The effect was not double. That fits a picture where the two receptors overlap substantially and GIP contributes an additional slice instead of a separate mechanism, which is also what the cagrilintide data showed with a different second target.
Its own cardiovascular trial established non-inferiority against another GLP-1 drug in people with diabetes. [10] Whether more weight loss eventually produces more event reduction is a reasonable expectation and it has not been tested.
What each one actually costs, and why the retail gap misleads
| Route | Semaglutide | Tirzepatide |
|---|---|---|
| Commercial insurance plus savings card | As low as $25 | As low as $25 |
| Manufacturer direct, self-pay | About $349 a month | $299 at 2.5 mg, $399 at 5 mg, $449 above that |
| Retail list, no programme | About $1,349 | About $1,086 |
The self-pay gap is smaller than people expect. At maintenance doses the difference between the two is roughly $100 a month, which is not nothing and is far less than the retail prices suggest. Both manufacturers cut direct prices sharply during 2025 and 2026 in response to each other. [11]
The cheapest route is now a pill. Novo Nordisk launched an oral Wegovy in January 2026, the first oral GLP-1 approved specifically for weight loss, at $149 to $299 a month through its direct pharmacy. [11] Tirzepatide has no oral form.
Treat every figure here as perishable. These prices moved several times in the eighteen months before this was written, and both companies are competing on them directly. Check the manufacturer's own pharmacy before relying on any number, including these.
Four gaps, and the first is the design of the trial everyone cites
Nobody has run a blinded head-to-head.SURMOUNT-5 was open-label, in a trial measuring an outcome that responds to effort and expectation. [1] A double-blind comparison would settle how much of the 6.5 point gap is pharmacology.
Trial conditions are not clinic conditions.A six month retrospective cohort in US clinical practice found the same direction of effect outside a trial setting, and real-world adherence, dosing and follow-up all differ from a study where people are monitored for 72 weeks. [3]
Nobody has compared them head to head on outcomes.SELECT showed semaglutide reducing events by 20 percent against placebo in people without diabetes. [9] SURPASS-CVOT showed tirzepatide non-inferior to another GLP-1 drug in people with diabetes. [10] Those are not the same claim, and the only direct cardiovascular comparison is a post-hoc analysis using a predicted risk score rather than counted events. [2]
Nobody knows the fat and lean tissue split, or what happens after.At 20 percent weight loss the question of what came off matters, and it is not the headline figure in either programme. Both drugs also show weight regain on discontinuation, and no trial has compared them on what happens when people stop.
Both carry the same boxed warning, and the difference is in the dosing experience
The same boxed warning for both
The strongest warning the FDA issues, and it applies to the class.
- Risk of thyroid C-cell tumours. Rodents developed dose-dependent tumours at clinically relevant exposures [6]boxed
- Contraindicated with a personal or family history of medullary thyroid carcinoma, or with MEN 2 [6]contraindicated
- Pancreatitis and gallbladder disease are labelled warnings for both [6]label
- Whether these tumours occur in humans is unknown, and no confirmed cases have emerged from the trial programmesunknown
From the head-to-head
Gastrointestinal effects dominate for both, and are dose dependent.
- Nausea, vomiting, diarrhoea and constipation, most pronounced during dose escalation [1]measured
- Most events were mild to moderate in both arms [1]measured
- Hair loss appears among the common adverse events on both labels, and rarely in coverage [6]label
- Weight reduction was about 6 percent lower in men than women, for both drugs [1]measured
What you are actually buying
Both have approved products, and a large market that is not them.
- Both are dispensed on prescription as manufactured productsrx only
- Compounded versions circulate widely and are not the approved product [12]not approved
- Testing of seized peptides found purity between 5 and 75 percent, plus arsenic and lead [7]analysis
- One US lab reported problems in almost 30 percent of samples, including bacteria [8]testing
*Where this page says nothing is established, it means nobody has studied it. It does not mean a compound is safe.
The boxed warning needs context in both directions. It exists because rodents given GLP-1 drugs developed thyroid C-cell tumours in a dose-dependent way, and rodents carry far more of the relevant receptors on those cells than people do. Whether it happens in humans is unknown, and no confirmed cases have come out of the trial programmes. [6] It also carries a hard contraindication, and a prescriber is meant to ask about your family's thyroid history before writing either drug. Our guide on reading a certificate of analysis covers what to look for in anything bought outside a pharmacy.
Both approved, with different additional indications
Sport. Neither semaglutide nor tirzepatide appears on the 2026 WADA Prohibited List. Weight class sports are where this could matter, since rapid weight loss has obvious competitive relevance, and WADA states that absence from the list does not mean a substance is permitted. Compounded versions carry the usual risk that a vial contains something the label never mentioned. If you compete under a testing body, ask that body directly.
Semaglutide is approved three times over. As Ozempic for type 2 diabetes, as Wegovy for chronic weight management, and as Rybelsus in tablet form for diabetes. Wegovy also carries an approval for reducing cardiovascular risk in certain adults with established cardiovascular disease and obesity or overweight.
Tirzepatide is approved twice. As Mounjaro for type 2 diabetes and as Zepbound for chronic weight management. Zepbound additionally carries an approval for moderate to severe obstructive sleep apnoea in adults with obesity, which semaglutide does not. Both also exist in a large compounded market that is not the approved product, and a compounded preparation is not checked by the FDA for safety, quality or effectiveness the way a manufactured drug is. [12]
Questions people ask
Which is better for weight loss, semaglutide or tirzepatide?
Tirzepatide, in the one trial that compared them directly. 20.2 percent against 13.7 over 72 weeks in 751 adults, and superior on all five key secondary endpoints. [1] The trial was open-label, which is a real limitation in a weight loss study.
Is tirzepatide really 47 percent better than semaglutide?
That figure is relative, not absolute. The gap between 20.2 and 13.7 is 6.5 percentage points, and expressing it as a proportion of 13.7 gives 47 percent. Both are accurate descriptions of the same result. [1]
What is the difference between them?
Semaglutide activates one receptor, GLP-1. Tirzepatide activates two, GLP-1 and GIP. The second receptor is the entire difference, and the trial measured what it adds.
Is Wegovy the same as Ozempic? Is Zepbound the same as Mounjaro?
Yes in both cases. Wegovy and Ozempic are both semaglutide, and Zepbound and Mounjaro are both tirzepatide. The pairs differ in approved indication and dose range, not in the molecule. Ozempic and Mounjaro are approved for type 2 diabetes, while Wegovy and Zepbound are approved for weight management.
Can you switch from semaglutide to tirzepatide?
People do, and the head-to-head trial does not answer what happens when you switch, because it randomised people who had not been on either. [1] Dose titration starts again from the bottom with the new drug, and switching is a prescriber's decision.
Can you take semaglutide as a pill?
Yes, and since January 2026 there is an oral Wegovy approved specifically for weight loss, alongside Rybelsus for diabetes. [11] Tirzepatide has no oral form, so for anyone who will not inject, that decides it regardless of the weight loss numbers.
Which is cheaper, semaglutide or tirzepatide?
At manufacturer self-pay prices they are close: about $349 a month for Wegovy against $299 to $449 for Zepbound depending on dose. With commercial insurance and a savings card, both can reach about $25. Retail list prices are roughly $1,349 and $1,086, and almost nobody pays them. The cheapest route overall is the oral Wegovy at $149 to $299. Prices here change frequently, so check the manufacturer's own pharmacy. [11]
Can I still get a compounded version?
Largely no. The FDA declared the tirzepatide shortage resolved in October 2024 and enforcement discretion ended in early 2025, and in April 2026 the agency proposed removing semaglutide from the 503B bulk list. [12] Compounded versions were never the approved products, and every trial result on this page belongs to the manufactured ones.
Do they both have a boxed warning?
Yes, the same one, for thyroid C-cell tumours based on rodent studies. Both are contraindicated with a personal or family history of medullary thyroid carcinoma or with MEN 2. [6]
What are the side effects?
Gastrointestinal effects dominate for both: nausea, vomiting, diarrhoea and constipation, mostly during dose escalation and mostly mild to moderate. [1] Hair loss appears among the common adverse events on both labels and is rarely mentioned in coverage. [6]
Does one protect the heart better?
Semaglutide has the stronger evidence at present. SELECT showed a 20 percent reduction in major cardiovascular events against placebo in 17,604 people with existing heart disease and obesity but no diabetes. [9] Tirzepatide's outcome trial, SURPASS-CVOT, showed non-inferiority against another GLP-1 drug in people with diabetes, which establishes safety rather than benefit. [10] No trial has compared the two on events.
How big is semaglutide's heart benefit in absolute terms?
The 20 percent figure is relative. It moved the event rate from 8.0 percent on placebo to 6.5 percent, a difference of 1.5 percentage points, with a number needed to treat of 67 over the trial period. [9] That is the same relative-versus-absolute distinction that applies to the weight loss comparison on this page.
Which has fewer side effects?
Neither clearly. In the head-to-head, gastrointestinal effects dominated in both arms, were mostly mild to moderate, and occurred mainly during dose escalation. [1] A narrative review comparing across trials put gastrointestinal adverse events at roughly 17 to 22 percent for tirzepatide and around 18 percent for semaglutide, which is close enough to call similar.
How much weight can you lose on each?
In the trial that compared them over 72 weeks, the average was 22.8 kilograms on tirzepatide and 15.0 on semaglutide. [1] Roughly one in five people on tirzepatide lost 30 percent or more of their body weight, against one in fifteen on semaglutide.
Will I regain the weight if I stop?
Both drugs show weight regain on discontinuation. No trial has compared them on what happens after stopping.
The published record
What Europe PMC and ClinicalTrials.gov hold for each, on the same rule.
Semaglutide has 500 records to Tirzepatide's 500. 127 original human studies against 126. Semaglutide has 754 registered trials to Tirzepatide's 285.
Semaglutide: FDA via DailyMed: Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus; to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease; to reduce the risk of sustained eGFR decline, end-stage kidney disease and cardiovascular death in adults with type 2 diabetes and chronic kidney disease · FDA via DailyMed: Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus; to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes who are at high risk for these events · FDA via DailyMed: Indicated in combination with a reduced calorie diet and increased physical activity to reduce the risk of major adverse cardiovascular events in adults with established cardiovascular disease and either obesity or overweight; to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 12 years and older with obesity and adults with overweight with at least one weight-related comorbid condition; for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis
Tirzepatide: FDA via DailyMed: Indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus; to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus who are at high risk for these events · FDA via DailyMed: Indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition; to treat moderate to severe obstructive sleep apnea in adults with obesity
The published record
6,371
Papers and trials about Semaglutide
261 papers with human data · 127 original studies
754 registered trials · 18 with posted results
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus; to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease; to reduce the risk of sustained eGFR decline, end-stage kidney disease and cardiovascular death in adults with type 2 diabetes and chronic kidney diseaseRegulatorsCounted from Europe PMC indexing, not read by a person; human includes reviews and cell work, original studies exclude both. 400 papers and 100 trials indexed in detail.
The published record
2,816
Papers and trials about Tirzepatide
270 papers with human data · 126 original studies
285 registered trials · 14 with posted results
Indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus; to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus who are at high risk for these eventsRegulatorsCounted from Europe PMC indexing, not read by a person; human includes reviews and cell work, original studies exclude both. 400 papers and 100 trials indexed in detail.
What this page is built on
- 01Aronne LJ, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. Published May 2025, presented at the European Congress on Obesity, Malaga. SURMOUNT-5. Human Phase 3b, open-label, active comparator, 751 adults with obesity and without diabetes, 72 weeks, maximum tolerated dose in both arms. Least-squares mean weight change 20.2 percent for tirzepatide against 13.7 percent for semaglutide, p less than 0.001. Absolute weight loss 22.8 kg against 15.0 kg. Waist circumference 18.4 cm against 13.0 cm. Reaching 10 percent loss: 81.6 against 60.5 percent. 20 percent: 48.4 against 27.3. 30 percent: 19.7 against 6.9. Gastrointestinal events most common in both arms, mostly mild to moderate and occurring during dose escalation. Weight reduction was about 6 percent lower in men than women for both drugs, and this trial enrolled a higher proportion of men than previous trials.
- 02Mamas MA, Bays H, Li R, et al. Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial. Eur Heart J Open. 2 September 2025. DOI 10.1093/ehjopen/oeaf117. Post-hoc analysis using a predicted 10-year cardiovascular risk score, not counted events. Average predicted 10-year risk before treatment 9.3 percent. Absolute reduction 2.4 percentage points for tirzepatide against 1.4 for semaglutide, p less than 0.001. Six of the eight authors were employees of Eli Lilly and Company, the trial sponsor.
- 03Comparative effectiveness of tirzepatide and semaglutide for obesity management in US clinical practice: a 6-month retrospective cohort study. Real-world retrospective cohort. Same direction of effect outside trial conditions, with the usual limits of observational data on adherence, dosing and follow-up.
- 04Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021. STEP 1. Human Phase 3, 68 weeks, adults with obesity without diabetes, semaglutide 2.4 mg weekly, around 15 percent weight loss.
- 05Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. PMID 35658024. SURMOUNT-1. Human Phase 3, 72 weeks, 2,539 adults. The 15 mg dose produced 22.5 percent weight loss on the efficacy estimand and 20.9 percent on the treatment-regimen estimand. The two figures differ in how they handle participants who stopped treatment, and both are correct.
- 06WEGOVY, OZEMPIC, RYBELSUS, MOUNJARO and ZEPBOUND prescribing information. Novo Nordisk and Eli Lilly. FDA labels. Both compounds carry a boxed warning for risk of thyroid C-cell tumours, based on rodent studies showing dose-dependent and duration-dependent tumours at clinically relevant exposures. Whether they occur in humans is unknown. Both are contraindicated with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia syndrome type 2. Labelled warnings include pancreatitis and gallbladder disease. Hair loss appears among common adverse events.
- 07Janvier S, Cheyns K, Canfyn M, Goscinny S, De Spiegeleer B, Vanhee C, Deconinck E. Impurity profiling of the most frequently encountered falsified polypeptide drugs on the Belgian market. Talanta. 2018;188:795-807. Peer-reviewed analytical study. Purity 5 to 75 percent, plus arsenic and lead.
- 08NBC Washington. Lab finds problems in 30% of peptide vials tested. December 2024. News report of commercial laboratory testing, not peer reviewed.
- 09Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023. SELECT. Human randomised, double-blind, placebo-controlled cardiovascular outcome trial. 17,604 adults aged 45 and over with pre-existing cardiovascular disease, BMI 27 or above, and no history of diabetes, across 804 sites in 41 countries. 20 percent reduction in major adverse cardiovascular events, hazard ratio 0.80, p less than 0.001. Absolute reduction 1.5 percentage points, from 8.0 percent on placebo to 6.5 percent, giving a number needed to treat of 67. Benefit emerged early, with a 38 percent reduction in the first three months when average weight loss was under 5 percent and before top dose.
- 10SURPASS-CVOT. Human cardiovascular outcome trial. 13,299 adults with type 2 diabetes and established atherosclerotic cardiovascular disease, comparing tirzepatide against dulaglutide as active comparator. Tirzepatide was non-inferior for three-point MACE, hazard ratio approximately 0.90 to 0.95, directionally favouring tirzepatide without meeting superiority. The comparator was another GLP-1 drug with its own cardiovascular approval, not placebo, so the trial establishes cardiovascular safety rather than benefit against no treatment.
- 11Manufacturer direct pricing, as of mid-2026. LillyDirect self-pay for Zepbound: $299 a month at 2.5 mg, $399 at 5 mg, and $449 at 7.5 mg through 15 mg. NovoCare Pharmacy self-pay for Wegovy injection: about $349 a month for doses up to 2.4 mg. Oral Wegovy launched 5 January 2026 as the first oral GLP-1 approved specifically for weight loss, at $149 to $299 a month. Retail list prices approximately $1,349 for Wegovy and $1,086 for Zepbound. With commercial insurance and a manufacturer savings card, both can fall to about $25 a month; savings cards are generally unavailable to Medicare, Medicaid, VA and TRICARE beneficiaries. These figures moved repeatedly during 2025 and 2026 and should be checked against the manufacturers' own pharmacies before use.
- 12Compounding status. The FDA declared the tirzepatide shortage resolved on 2 October 2024, with enforcement discretion for large-scale compounding ending in approximately February to March 2025. In April 2026 the agency proposed removing semaglutide from the 503B bulk drug substances list, which would end large-scale compounding of semaglutide once finalised.