GLP-1 alternatives: 9 non-GLP-1 options with evidence and prices
GLP-1 alternatives fall into three groups. Approved non-GLP-1 drugs: Qsymia, Contrave, orlistat (Xenical or Alli) and short-term phentermine. Non-drug options: Plenity, structured lifestyle programs, bariatric surgery and endoscopic sleeve gastroplasty. Metformin is sometimes used off-label. Surgery produces the largest average loss; lifestyle programs cost least.
The medication in brief
GLP-1 medicines such as semaglutide (Wegovy, Ozempic), tirzepatide (Zepbound, Mounjaro) and orforglipron (Foundayo) mimic a gut hormone that slows stomach emptying and reduces appetite. On their labels they produce the largest average weight loss of any approved drug class. Self-pay, the Wegovy pill starts at $149 a month (NovoCare Wegovy price page, checked 5 Oct 2026) and Zepbound costs $299 to $449 (Zepbound savings page, checked 5 Oct 2026). People look past them because of that ongoing cost, nausea and other GI effects, a thyroid C-cell boxed warning that rules out anyone with a history of MTC or MEN 2, or a wish to avoid weekly injections and long-term medication altogether.
Why people look for alternatives
A contraindication
GLP-1 labels carry a boxed warning about thyroid C-cell tumors and rules out anyone who has had medullary thyroid carcinoma, has a relative who has, or has MEN 2 (Wegovy and Zepbound labels). None of the non-GLP-1 drugs below has that warning.
Monthly cost that never stops
A year of Zepbound at $449 a month is $5,388 self-pay (Zepbound savings page, checked 5 Oct 2026). Several alternatives cost under $100 a month, and surgery is a one-time cost.
Side effects
Nausea, vomiting, diarrhea and constipation are the most common GLP-1 reactions on their labels. Some people cannot tolerate them even after slow dose steps.
No insurance coverage
Many plans exclude weight-loss drugs. Medicare Part B covers the Diabetes Prevention Program at no cost for people who qualify (Medicare.gov), and surgery is often covered when criteria are met.
Wanting a non-drug route
Some people prefer a device, a procedure or a structured program to taking a medicine indefinitely, or want an option to try first.
How we compared
Drug evidence comes from each product's FDA label on DailyMed. For devices, programs and procedures we used the main trial or cohort paper (GLOW, the Diabetes Prevention Program, Look AHEAD, MERIT, and the PCORnet bariatric study). Prices come from the seller's own page or price list, read on 5 October 2026. Procedure prices vary widely by region, so we quote named sellers. Nothing was tested by us.
Prices checked on October 5, 2026
Alternatives
Qsymia (phentermine and topiramate ER)
- Kind
- FDA-approved other weight-loss drug
- How it differs
- A once-daily capsule: phentermine curbs appetite and topiramate, an anti-seizure drug, adds to the effect. Approved for long-term weight management. Schedule IV.
- Evidence
Across two 56-week trials on the label, the top dose (15 mg/92 mg) produced average losses of 10.9% and 9.8%, against 1.6% and 1.2% on placebo, and 67% to 70% of people on it lost at least 5% (Qsymia label). It is contraindicated in pregnancy, glaucoma and hyperthyroidism and is sold under a REMS program.
- Starting price
- $75 per 30-day prescription with the manufacturer discount, or $65.99 cash for Costco members (Qsymia.com, checked 5 Oct 2026)
- Best for
- Adults who want the largest average loss among non-GLP-1 drugs, at a low fixed price
- Tradeoffs
- Controlled substance; Temi does not prescribe it. Tingling, dizziness, altered taste, insomnia, constipation and dry mouth are common.
Contrave (naltrexone and bupropion ER)
- Kind
- FDA-approved other weight-loss drug
- How it differs
- An extended-release tablet taken twice a day that acts on appetite and reward pathways in the brain. Approved for chronic weight management. Not controlled.
- Evidence
COR-I, a 56-week placebo-controlled trial, found a mean weight change of -5.4% with Contrave and -1.3% without it; when paired with intensive behavioral counseling in COR-BMOD it was -8.1% versus -4.9% (Contrave label). Because bupropion is an antidepressant, Contrave has a boxed warning about suicidal thoughts.
- Starting price
- $99 a month including shipping via the CurAccess Patient Support Program (Contrave.com, checked 5 Oct 2026)
- Best for
- People with food cravings or emotional eating who want a non-controlled oral option
- Tradeoffs
- Nausea, constipation and headache are common. Not for people with seizures, uncontrolled blood pressure or taking opioids.
Phentermine (Lomaira or generic)
- Kind
- FDA-approved other weight-loss drug
- How it differs
- A stimulant-type appetite suppressant approved for short-term use only, a few weeks, as part of a diet and exercise plan. Schedule IV.
- Evidence
The Lomaira label says that in short-term trials, people on drugs of this type lost more than those on placebo, but the extra loss was "only a fraction of a pound a week" and slowed after the first weeks. Warnings include primary pulmonary hypertension and heart valve disease, and combining it with other weight-loss products has not been shown safe.
- Starting price
- Lomaira 8 mg costs at most 50 cents per tablet with the Lo-Cost Access Program card (lomaira.com, checked 5 Oct 2026)
- Best for
- A short, supervised course when budget is the main constraint
- Tradeoffs
- Not for long-term use on its label. Raises heart rate and blood pressure; can cause insomnia. Controlled, so Temi does not prescribe it.
Orlistat (Xenical 120 mg, or Alli 60 mg over the counter)
- Kind
- FDA-approved other weight-loss drug
- How it differs
- Blocks the gut enzymes that digest fat, so part of the fat in each meal passes through unabsorbed. Taken with fat-containing meals. Alli needs no prescription.
- Evidence
In the 4-year XENDOS study on the Xenical label, 73% of people on orlistat lost at least 5% of body weight in the first year versus 45% on placebo, but after four years the average difference from placebo was 2.5%. New diabetes was less common on orlistat (5.5% vs 8.3%). Oily spotting hit 26.6% of users in year one versus 1.3% on placebo.
- Starting price
- Alli: $45.49 for a 60-capsule starter pack, about 20 days at the maximum of 3 capsules a day (Amazon listing, checked 5 Oct 2026)
- Best for
- People who want to start without a prescription, or who eat a higher-fat diet they are ready to cut back
- Tradeoffs
- GI effects worsen with fatty meals. Can reduce absorption of fat-soluble vitamins, so the label advises a multivitamin taken apart from doses. Smallest average effect here.
Metformin (off-label for weight)
- Kind
- FDA-approved other weight-loss drug
- How it differs
- A generic diabetes tablet that is not approved for weight loss. Prescribers sometimes use it off-label, mainly in prediabetes or insulin resistance.
- Evidence
Its label covers type 2 diabetes only. In one 29-week trial on the label in adults with obesity and diabetes, weight fell 8.4 lb on metformin alone versus 0.7 lb on glyburide. In the Diabetes Prevention Program, it cut new diabetes by 31% versus placebo, against 58% for the lifestyle program (NEJM 2002).
- Starting price
- Generic 500 mg: $5.32 for 30 tablets before Cost Plus Drugs' $5.25 shipping charge (Cost Plus Drugs price list, checked 5 Oct 2026)
- Best for
- Adults with prediabetes or type 2 diabetes for whom lowering blood sugar is the main goal
- Tradeoffs
- Modest, inconsistent weight effect. GI upset early. Boxed warning for rare lactic acidosis; not for people with significant kidney disease.
Plenity (oral hydrogel device)
- Kind
- non-drug option
- How it differs
- An FDA-cleared device, not a drug: capsules taken before meals release a gel that absorbs water and takes up space in the stomach. Now sold over the counter for BMI 25 to 40.
- Evidence
In the 24-week GLOW trial, average weight loss was 6.4% with Plenity against 4.4% with placebo, and 59% versus 42% lost at least 5% (Obesity 2019). The trial did not meet its stricter goal of beating placebo by 3 points. It is not absorbed into the bloodstream.
- Starting price
- $100 to $125 a month depending on bundle length (3, 6 or 12 months); no 1-month option (Plenity FAQ, checked 5 Oct 2026)
- Best for
- People with overweight or mild obesity who want a non-drug aid without a prescription
- Tradeoffs
- Only 2 points better than placebo on average in one 24-week trial. Sold in 3- to 12-month bundles; HSA and FSA payment accepted through Truemed.
Structured lifestyle program (DPP, WeightWatchers and similar)
- Kind
- non-drug option
- How it differs
- Coached diet, activity and behavior change over months, in person or online. No medicine. The National DPP is a year-long CDC-recognized program for people with prediabetes.
- Evidence
In the Diabetes Prevention Program, the lifestyle arm, aiming for 7% weight loss and 150 minutes of activity a week, cut new diabetes by 58% versus placebo (NEJM 2002). In Look AHEAD, adults with type 2 diabetes kept off 4.7% of their weight at 8 years versus 2.1% with usual care, and half kept off at least 5% (Obesity 2014).
- Starting price
- $0 in Medicare's DPP if eligible (Medicare.gov); WeightWatchers $25 first month, then $74 a month on a 12-month plan (weightwatchers.com, checked 5 Oct 2026)
- Best for
- Anyone with prediabetes, and anyone who wants the foundation every other option on this page is designed to sit on
- Tradeoffs
- Smaller average loss than drugs or procedures, and results depend on sustained effort. WeightWatchers plans auto-renew; medication costs extra.
Bariatric surgery (sleeve gastrectomy or gastric bypass)
- Kind
- non-drug option
- How it differs
- Surgery that permanently reduces stomach size (sleeve) or also reroutes the small intestine (bypass). A one-time procedure followed by lifelong follow-up visits.
- Evidence
In a 65,093-patient PCORnet cohort, average total weight loss at 1 year was 31.2% after gastric bypass and 25.2% after sleeve, and 25.5% and 18.8% at 5 years. Major complications within 30 days occurred in 5.0% after bypass and 2.6% after sleeve (Ann Intern Med 2018). It was an observational study, not a randomized trial.
- Starting price
- Self-pay from $9,950 for a sleeve or $14,100 for a bypass at one Alabama practice, before labs and some extras (Madison Surgical Associates, checked 5 Oct 2026)
- Best for
- People with severe obesity or obesity-related disease who want the largest and most durable average loss
- Tradeoffs
- Surgical risk, recovery time and permanent anatomy change. Average loss in the PCORnet cohort was lower at 5 years than at 1 year.
Endoscopic sleeve gastroplasty (ESG)
- Kind
- non-drug option
- How it differs
- A doctor stitches the stomach into a narrower tube from the inside, using an endoscope passed through the mouth. No incisions, and no part of the stomach is removed.
- Evidence
In the MERIT randomized trial of adults with class 1 or 2 obesity, ESG plus lifestyle changes produced 13.6% average total weight loss at 52 weeks versus 0.8% with lifestyle changes alone; 68% kept at least 25% of excess weight off at 104 weeks. Serious procedure-related events occurred in 2% (Lancet 2022).
- Starting price
- $7,160 to $15,708 upfront through MDsave, depending on provider (MDsave, checked 5 Oct 2026); Everself lists $12,995
- Best for
- People with class 1 or 2 obesity who want a procedure without incisions or permanent removal of stomach tissue
- Tradeoffs
- Cash prices vary more than twofold between providers. Less average loss than surgery. MERIT enrolled only people who agreed to lifelong diet restrictions.
Which to choose
| If you | Consider | Why |
|---|---|---|
| Have a history of MTC or MEN 2 and cannot take a GLP-1 | Qsymia or Contrave | Both are approved for long-term weight management without the thyroid C-cell warning. Ask which fits your other conditions. |
| Have prediabetes | A Diabetes Prevention Program, with or without metformin | In the DPP, the lifestyle program cut new diabetes by 58% and metformin by 31%. Medicare covers the program at no cost if you qualify. |
| Want to start today without a prescription | Alli or Plenity | Both are sold over the counter. Expect modest average effects and GI side effects with either. |
| Have severe obesity or diabetes that drugs have not controlled | Bariatric surgery | It produced the largest average loss of any option here, 25% to 31% at one year in the PCORnet cohort. Ask a bariatric program about eligibility. |
| Want a procedure but not surgery | Endoscopic sleeve gastroplasty | MERIT showed 13.6% average loss at a year without incisions, at a cash price that usually starts above $7,000. |
| Need the lowest possible cost for a short time | Phentermine | At no more than 50 cents a tablet it is the cheapest drug here, but it is approved for a few weeks only. |
Switching
If you are moving from a GLP-1 to one of these, plan the change with a prescriber rather than stopping on your own. Weight often returns after a GLP-1 is stopped, which our post on what happens when you stop taking a GLP-1 covers, and some options here, such as Qsymia and phentermine, have their own screening first. Ask: should I overlap or taper, and what should I watch for in the first month? For changing who prescribes, see our guide to switching GLP-1 providers without interrupting treatment.
Frequently asked questions
What is the best alternative to GLP-1 for weight loss?
It depends on your health and budget. On average effect alone, bariatric surgery leads (18.8% to 25.5% at five years in the PCORnet cohort), then ESG (13.6% at one year in MERIT), then Qsymia (9.8% to 10.9% at one year on its label). Contrave, orlistat and Plenity average less. Ask a prescriber which fits your conditions.
Is there a non-prescription alternative to GLP-1 drugs?
Yes. Alli (orlistat 60 mg) is FDA-approved for over-the-counter use in overweight adults, and Plenity is an FDA-cleared device now sold without a prescription for a BMI of 25 to 40. Both have smaller average effects than prescription GLP-1s. Supplements marketed as "natural GLP-1" are not FDA-approved for weight loss.
What is the cheapest GLP-1 alternative?
A lifestyle program can cost nothing: Medicare covers its Diabetes Prevention Program at no cost for eligible members. Among drugs, generic metformin costs $5.32 for 30 tablets at Cost Plus Drugs and Lomaira is capped at 50 cents a tablet with its savings program (both checked 5 Oct 2026). Neither is as effective on average as a GLP-1.
Does metformin work like a GLP-1?
No. Metformin mainly lowers the liver's glucose output and does not slow stomach emptying the way GLP-1 drugs do. It is not FDA-approved for weight loss, and its weight effect in trials is small and variable. It does reduce the chance of developing diabetes: 31% fewer cases than placebo in the Diabetes Prevention Program.
Is bariatric surgery better than GLP-1 medication?
It produces larger average loss than any drug label reports: 25.2% to 31.2% at one year in the PCORnet cohort, versus 20.9% for tirzepatide 15 mg at 72 weeks in SURMOUNT-1. But it carries surgical risk and permanent change, while drugs work only while taken. Ask a bariatric program whether you qualify.
Can Temi prescribe a GLP-1 alternative?
For non-controlled medicines, yes, subject to physician review: a new prescription review is $79 and refills are $15 (usetemi.com, checked 5 Oct 2026). That can include metformin. Temi does not prescribe controlled substances, so Qsymia and phentermine are not available through it, and it does not perform procedures.
Sources
- Wegovy (semaglutide) injection and tablets prescribing information, DailyMed (checked October 5, 2026)
- Wegovy pill and pen self-pay prices, NovoCare (Novo Nordisk) (checked October 5, 2026)
- Zepbound (tirzepatide) prescribing information, DailyMed (checked October 5, 2026)
- Zepbound coverage and savings, including LillyDirect self-pay prices (Eli Lilly) (checked October 5, 2026)
- Qsymia (phentermine and topiramate extended-release) prescribing information, DailyMed (checked October 5, 2026)
- Qsymia cost and savings options (Vivus) (checked October 5, 2026)
- Contrave (naltrexone and bupropion extended-release) prescribing information, DailyMed (checked October 5, 2026)
- Contrave cost and savings, CurAccess program (Currax) (checked October 5, 2026)
- Lomaira (phentermine hydrochloride) prescribing information, DailyMed (checked October 5, 2026)
- Lomaira Lo-Cost Access Program: no more than 50 cents per tablet (KVK-Tech) (checked October 5, 2026)
- Xenical (orlistat) prescribing information, including the 4-year XENDOS study, DailyMed (checked October 5, 2026)
- alli (orlistat 60 mg) 60-capsule starter pack, Amazon.com listing (checked October 5, 2026)
- Metformin hydrochloride tablets prescribing information, DailyMed (checked October 5, 2026)
- Cost Plus Drugs cash price list (metformin, dapagliflozin, liraglutide), via the Cost Plus Drugs pricing API (checked October 5, 2026)
- Knowler WC et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin (Diabetes Prevention Program). NEJM 2002;346:393-403 (checked October 5, 2026)
- Greenway FL et al. A randomized, double-blind, placebo-controlled study of Gelesis100 (GLOW). Obesity 2019;27:205-216 (checked October 5, 2026)
- Plenity FAQ: over-the-counter status, eligibility and bundle prices (tryplenity.com) (checked October 5, 2026)
- Look AHEAD Research Group. Eight-year weight losses with an intensive lifestyle intervention. Obesity 2014;22:5-13 (checked October 5, 2026)
- Medicare Diabetes Prevention Program coverage, Medicare.gov (checked October 5, 2026)
- National Diabetes Prevention Program lifestyle change program, CDC (checked October 5, 2026)
- WeightWatchers plans and membership pricing (WW International) (checked October 5, 2026)
- Arterburn D et al. Comparative effectiveness and safety of bariatric procedures for weight loss: a PCORnet cohort study. Ann Intern Med 2018;169:741-750 (checked October 5, 2026)
- Self-pay bariatric surgery prices (sleeve from $9,950, bypass from $14,100), Madison Surgical Associates, Huntsville, Alabama (checked October 5, 2026)
- Abu Dayyeh BK et al. Endoscopic sleeve gastroplasty for class 1 and 2 obesity (MERIT): a randomised trial. Lancet 2022;400:441-451 (checked October 5, 2026)
- How much does an endoscopic sleeve cost? Upfront price range, MDsave (checked October 5, 2026)
- Weight loss procedure pricing (ESG, gastric balloon), Everself (checked October 5, 2026)
- Get prescribed: $79 one-time doctor review for a new non-controlled prescription (Temi) (checked October 5, 2026)
- Prescription refills, $15 per refill review (Temi) (checked October 5, 2026)
Compounded semaglutide and compounded tirzepatide are not FDA-approved generics of the brand-name products. A licensed 503A compounding pharmacy prepares each one for a single prescription.
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