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Tirzepatide

Photo: HealthVetted editorial render
Semaglutide
| # | Product | Active ingredient | Starting price | FDA status | Score | |
|---|---|---|---|---|---|---|
| 1 | Mounjaro | Tirzepatide | Best ·$1349/mo | off-label | Top ·7.8 | See offer → |
| 2 | Wegovy | Semaglutide | Best ·$1349/mo | approved | 7.7 | See offer → |
Mounjaro's active ingredient, tirzepatide, is a "dual agonist" that activates two gut-hormone receptors at once: GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1). Most older drugs in this class hit only GLP-1. By stimulating both, tirzepatide prompts the pancreas to release insulin when blood sugar is high, lowers the glucagon hormone that raises blood sugar, slows how fast the stomach empties, and reduces appetite. The net effect is better blood-sugar control and, as a downstream benefit, significant weight loss. A built-in fatty-acid chain lets it bind to blood albumin, giving it a long half-life so it only needs to be injected once a week.
Wegovy's active ingredient, semaglutide, mimics a natural gut hormone called GLP-1 (glucagon-like peptide-1). By activating GLP-1 receptors in the brain's appetite centers, it reduces hunger, increases feelings of fullness, and slows how quickly the stomach empties. The result is that most people naturally eat less and feel satisfied on smaller portions. It also improves how the body handles blood sugar. Because it does not "burn fat" directly, it works largely by lowering calorie intake, which is why diet and physical activity remain part of treatment.
In SURPASS-2, an open-label 40-week head-to-head trial of 1,879 adults with type 2 diabetes published in the New England Journal of Medicine (2021), tirzepatide beat injectable semaglutide 1 mg. In the primary (treatment-regimen) analysis, the 15 mg dose lowered A1C by about 2.30 percentage points and reduced body weight by roughly 11.2 kg (about 12% from a baseline near 94 kg), and the 5 mg dose lowered A1C by about 2.01 points with about 7.6 kg lost — versus 1.86 points and 5.7 kg with semaglutide. (In the secondary on-treatment analysis, 15 mg figures were larger, about 2.46 points and 12.4 kg.) About 60% of participants on 15 mg hit a combined target of A1C 6.5% or lower plus at least 10% weight loss, compared with 22% on semaglutide. In the separate SURPASS-CVOT outcomes trial (about 13,300 patients with type 2 diabetes and established atherosclerotic heart disease, ~4-year median follow-up, published in NEJM in 2025), tirzepatide was non-inferior to dulaglutide for major adverse cardiovascular events (HR 0.92) and showed a 16% lower rate of all-cause death (HR 0.84), alongside greater A1C and weight reductions. These trials were in people with type 2 diabetes; your results may differ.
In the pivotal STEP 1 trial (NEJM, 2021; 1,961 adults with overweight or obesity but without diabetes), weekly semaglutide 2.4 mg produced an average weight loss of about 14.9% of body weight at 68 weeks versus roughly 2.4% with placebo, and about 86% of treated participants lost at least 5% of their body weight. The 2-year STEP 5 trial (Nature Medicine, 2022) showed sustained results with continued use: about 15.2% mean weight loss versus 2.6% with placebo at 104 weeks. In the large SELECT cardiovascular outcomes trial (NEJM, 2023; 17,604 adults with established cardiovascular disease, overweight or obese, without diabetes), semaglutide reduced major adverse cardiovascular events (cardiovascular death, non-fatal heart attack, non-fatal stroke) by 20% versus placebo (hazard ratio 0.80). The newer oral Wegovy 25 mg pill produced about 16.6% mean weight loss among participants who adhered to treatment in the OASIS 4 trial. Individual results vary.
The most common side effects are gastrointestinal: nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion, and abdominal pain. These are usually mild to moderate, most pronounced when starting and after each dose increase, and tend to ease over days to weeks. Serious but less common risks include acute pancreatitis (severe, persistent stomach pain — seek care immediately), gallbladder problems and gallstones (more likely during rapid weight loss), severe low blood sugar especially when combined with insulin or sulfonylureas, kidney injury from dehydration due to vomiting or diarrhea, allergic reactions, and possible worsening of diabetic retinopathy. The boxed warning concerns thyroid C-cell tumors seen in rodents; whether this risk applies to humans is unknown, so watch for a neck lump, hoarseness, trouble swallowing, or persistent shortness of breath and tell your doctor. Report any severe or persistent symptoms to your prescriber.
The most common side effects (each occurring in 5% or more of users in trials) are gastrointestinal: nausea, diarrhea, vomiting, constipation, abdominal pain, bloating, and indigestion, along with headache, fatigue, and dizziness. These are usually mild to moderate, tend to be worst when starting or increasing the dose, and often ease over a few weeks. Serious but less common risks include pancreatitis, gallbladder problems (including gallstones), acute kidney injury from dehydration caused by vomiting or diarrhea, low blood sugar (mainly in people also taking diabetes medications such as insulin or sulfonylureas), and worsening of diabetic eye disease. Wegovy carries a boxed warning for thyroid C-cell tumors based on rodent studies; whether this risk applies to humans is not known. Seek medical care promptly for severe, persistent abdominal pain (a possible sign of pancreatitis). This is not a complete list; review the full label and discuss risks with your prescriber.
As of 2026, Mounjaro's US list price is roughly $1,000-$1,080 for a one-month (four-pen) supply, with cash/retail prices often quoted between about $995 and $1,300 depending on pharmacy. With commercial insurance that covers Mounjaro for diabetes, Eli Lilly's Mounjaro Savings Card can drop the cost to as little as $25 per month (subject to a per-fill and annual cap). If you have commercial insurance that does NOT cover it, the savings card may bring it to as low as about $499/month. Federal rules bar manufacturer copay cards for people on Medicare, Medicaid, TRICARE, or VA. Medicare Part D may cover Mounjaro for type 2 diabetes (with formulary tier and prior-authorization rules) but does not cover GLP-1 drugs for weight loss. Off-label use for weight loss is increasingly denied by insurers. Confirm current pricing and your own coverage before starting.
As of 2026, Wegovy's list price is roughly $1,350 per month before insurance or discounts. Through Novo Nordisk's NovoCare self-pay program, eligible cash-paying patients without insurance can get the injection for about $349 per month for standard doses, with a limited-time promotional price near $199 per month for the lowest starter doses (0.25 mg and 0.5 mg) through mid-2026; the oral pill has its own self-pay pricing, generally lower. This self-pay price was lowered over time (it was about $499 per month in early 2025). With commercial (non-government) insurance that covers Wegovy, the manufacturer savings card can bring copays as low as $0 for eligible patients, but many plans, and most Medicare and Medicaid plans, still do not cover Wegovy for weight loss. Coverage and out-of-pocket costs vary widely and change frequently, so verify current pricing for your specific dose and plan directly with NovoCare and your pharmacy.
Mounjaro is FDA-approved as an add-on to diet and exercise to improve blood sugar control in adults and pediatric patients 10 years and older with type 2 diabetes. It is NOT FDA-approved for weight loss or for type 1 diabetes. It should NOT be used by anyone with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) — this is a boxed warning. Avoid or use with caution if you have a history of pancreatitis, severe gastrointestinal disease such as gastroparesis, diabetic retinopathy, or known hypersensitivity to tirzepatide. It is not recommended in pregnancy. Because delayed stomach emptying can reduce absorption of oral pills, Lilly advises people using oral hormonal contraceptives to switch to a non-oral method or add a barrier method for four weeks after starting and for four weeks after each dose increase. Discuss kidney issues and any history of gallbladder disease with your prescriber.
Wegovy is FDA-approved for adults with obesity (BMI 30 or higher) or overweight (BMI 27 or higher) who also have a weight-related condition such as high blood pressure, type 2 diabetes, or high cholesterol, used alongside a reduced-calorie diet and increased physical activity. It is also approved to reduce the risk of major cardiovascular events in adults with established cardiovascular disease who are overweight or obese, and for adolescents aged 12 and older with obesity. It is contraindicated in anyone with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), and in those with a known serious allergy to semaglutide or any Wegovy ingredient. It should not be used during pregnancy; because of semaglutide's long half-life, the label advises stopping at least 2 months before a planned pregnancy. Use cautiously, and under close supervision, with a history of pancreatitis, gallbladder disease, severe gastrointestinal disease, kidney problems, or diabetic retinopathy. A clinician determines eligibility.
Wegovy: Wegovy (semaglutide) is an FDA-approved GLP-1 medication for chronic weight management that produced about 15% average weight loss over 68 weeks in trials and cut major cardiovascular events 20% in adults with established heart disease who are overweight or obese. It works only while you keep taking it, costs roughly $349 per month cash through the manufacturer's self-pay program in 2026 (list price about $1,350), and commonly causes nausea and other GI side effects. Both are strong options — match the pick to your specific needs, budget, and clinician's guidance.
Editorial comparison, not medical advice. Discuss options with a qualified clinician. Individual results vary.