Examples of options we may consider after evaluating you; not everyone qualifies; some uses may be off‑label; risks/contraindications will be reviewed before prescribing.
Many primary care providers have begun prescribing GLP-1 receptor agonists for weight loss, recognizing their transformative efficacy demonstrated in recent trials.1-3 However, some remain unfamiliar with the latest and most effective agents, continuing to prescribe the older semaglutide (Wegovy) rather than the superior tirzepatide (Zepbound) in average weight loss outcomes.4,5 Additionally, many PCPs lack experience navigating the complex prior authorization process required by insurance companies, leaving patients to struggle through denials and appeals on their own—or simply giving up on treatment entirely.6
GLP-1 receptor agonists offer benefits far beyond weight loss: Major reduction in heart attacks and strokes, slowing of chronic kidney disease progression, and improvement of fatty liver disease (MASH), sleep apnea, inflammation markers, and chronic pain (notably knee osteoarthritis symptoms in obesity).7-13,16 Emerging research suggests potential neuroprotective benefits and reduction in addictive urges beyond food (early/limited human data; larger trials are ongoing).14,15 For patients with obesity plus these conditions, GLP-1s represent disease-modifying therapy addressing multiple aspects of metabolic dysfunction—not just a weight loss medication.7-9,12,16,22
Tirzepatide (Zepbound/Mounjaro)
As low as $349 per month
A dual GIP/GLP-1 receptor agonist that has demonstrated superior weight loss compared to semaglutide in head-to-head trials.3,5 While semaglutide produces average weight loss of ~15% in pivotal trials (often summarized clinically as ~15–17%), tirzepatide achieves ~20% average weight loss in pivotal trials, with a substantial subset of patients reaching ≥25%—approaching what was previously only possible with bariatric surgery for many patients.2,3,16,17 The dual mechanism (targeting both GIP and GLP-1 receptors) has a mechanistic rationale for broader metabolic effects; in practice, appetite suppression can be stronger for some patients, while tolerability is broadly similar at the population level (Tirzepatide may have a slight advantage) and varies by individual.3,5,22,23 For patients seeking maximum efficacy, tirzepatide should be the preferred agent when insurance coverage allows.5
Semaglutide (Ozempic/Wegovy)
As low as $149 per month
Semaglutide is somewhat inferior in average weight loss compared with tirzepatide (side effects vary by individual), but is now available from the official manufacturer pharmacy for as little as ~$149/month for certain starter doses of Wegovy.2,5,18-20 In some cases these differences can be a “toss up” for individual patients. We often prescribe this to cost-conscious patients for whom a GLP-1 is still the best option. Additionally, unlike Zepbound it comes in a pill for patients who like to avoid needles.18
Insurance Navigation
We have extensive experience with prior authorization requirements, appeal processes, and alternative coverage pathways for GLP-1 medications. Additional FDA approvals for sleep apnea and fatty liver (MASH) may help us get these paid for if your insurance does not cover them purely for weight loss.9-11 We handle prior authorizations and appeals by documenting diagnoses and medical necessity accurately and submitting the clinical information insurers require. When coverage is limited, we can also discuss manufacturer savings programs and other cost‑reduction pathways.19,20 Getting these medications approved requires expertise that goes beyond simply writing a prescription—we handle this process so you don’t have to.6
Traditional and Adjunctive Medications
The “Stacking” Approach
While GLP-1s represent the most powerful single agent class for weight loss, they’re expensive (often hundreds of dollars per month via self‑pay programs; list prices can exceed $1,000/month) and not always accessible.19-21 Moreover, combining GLP-1s with other weight loss medications can enhance results for selected patients, though strong randomized evidence for specific multi‑drug “stacks” is more limited than for the GLP‑1 agents themselves.22,23
We prescribe a wide array of older, generic medications that produce modest weight loss individually and can be combined when appropriate—meaning multiple agents can be used together to target different mechanisms.22,23 In our experience the combination of 3-5 traditional medications can produce results comparable to GLP-1 (semaglutide) monotherapy for some patients. Critically, many of these medications can be very low-cost with common discount programs, although others can cost more depending on the drug and pharmacy (notably naltrexone and prescription-strength orlistat).24-28
Bupropion (Wellbutrin)
As low as 3$ per month
Produces clinically meaningful weight loss in some patients and is commonly discussed as ~5–7% in the obesity pharmacotherapy literature; it works pharmacologically via dopamine and norepinephrine reuptake inhibition and nicotine modulation (mechanistic basis for effects on appetite/craving pathways is still being studied).22,23 Also addresses comorbid depression or low energy. Can be combined with naltrexone for enhanced effect (marketed as Contrave, but we can prescribe both generics separately for far less cost).22,23,24,27,29
Metformin
As low as 2$ per month
Beyond its diabetes indication, metformin produces modest weight loss (often ~2–3% in clinical studies and real-world use) by improving insulin sensitivity and reducing hepatic glucose production.22,23 Particularly valuable for patients with prediabetes, PCOS, or metabolic syndrome.22,23 Side benefit: may have longevity and anti-cancer signals in observational and mechanistic research, but this is not yet proven as a clinical outcome benefit in randomized longevity trials.22,23
Topiramate
As low as 3$ per month
Produces clinically meaningful weight loss in some patients (often summarized as ~5–10% in obesity pharmacotherapy reviews) through multiple mechanisms including appetite suppression and altered taste perception; cognitive side effects are dose-related.22,23 We use lower doses (25-100mg) than the epilepsy indication to minimize cognitive side effects while maintaining weight loss efficacy.22,23,26 Particularly effective when combined with other agents.22,23
Naltrexone
As low as 22$ per month
An opioid antagonist that is best supported in obesity when combined with bupropion (Contrave), where it targets appetite/reward circuitry; naltrexone monotherapy is not an FDA-approved weight-loss treatment and weight-loss data for naltrexone alone are more limited/variable.22,23,27 Synergistic when combined with bupropion.22,23,27
Orlistat
As low as 60$ per month
Works peripherally by blocking intestinal fat absorption (commonly described as ~30% of dietary fat at prescription dosing).22,23 Produces modest additional weight loss when combined with a reduced-calorie diet and is the only widely used anti-obesity medication that works outside the central nervous system.22,23 Gastrointestinal side effects (loose stools, urgency) can be significant with high-fat meals but can function as behavioral feedback for dietary adherence.22,23
Combination Strategies
We frequently combine 2-5 of these medications simultaneously for patients who need significant weight loss but can’t access or afford GLP-1s, or to enhance GLP-1 efficacy for patients who’ve plateaued. Evidence for specific multi-drug combinations is more practice-based than research-based, so exact numbers vary.22,23 For example: metformin + bupropion + topiramate can sometimes produce double‑digit weight loss at low monthly cost using discount programs, rivaling much more expensive branded combination products.22-26 When combined with a GLP-1 (especially tirzepatide), some patients reach ≥25% total weight loss though whether adding adjunctive agents meaningfully increases the odds beyond what GLP‑1 therapy alone can achieve is still an evolving evidence base.3,5,22,23
Our approach makes medical weight loss accessible regardless of insurance status, maximizes efficacy through rational polypharmacy, and ensures patients receive the most advanced agents (tirzepatide) when appropriate—along with the insurance navigation expertise to actually get them covered.
References
1. Blue Cross Blue Shield Association. *Issue Brief: Real-World Trends in GLP-1 Treatment Persistence and Prescribing for Weight Management.* Published May 2024. Accessed January 4, 2026. https://www.bcbs.com/media/pdf/BHI_Issue_Brief_GLP1_Trends.pdf
2. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. *N Engl J Med.* 2021;384:989-1002. doi:10.1056/NEJMoa2032183
3. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. *N Engl J Med.* 2022;387:205-216.
4. Ukhanova M, et al. Trends in glucagon-like peptide 1 receptor agonist prescribing patterns. *Am J Manag Care.* 2025;31(8):e228-e234.
5. Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393(1):26-36. doi:10.1056/NEJMoa2416394
6. American Medical Association. AMA survey indicates prior authorization wreaks havoc on patient care. Published June 18, 2024. Accessed January 4, 2026. https://www.ama-assn.org/press-center/ama-press-releases/ama-survey-indicates-prior-authorization-wreaks-havoc-patient-care
7. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. *N Engl J Med.* 2023;389:2221-2232.
8. Perkovic V, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. *N Engl J Med.* 2024.
9. U.S. Food and Drug Administration. FDA Approves Treatment for Serious Liver Disease Known as ‘MASH’. Content current as of August 15, 2025. Accessed January 4, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash
10. Wegovy (semaglutide) injection 2.4 mg prescribing information. U.S. Food and Drug Administration. Revised 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215256s024lbl.pdf
11. U.S. Food and Drug Administration. FDA approves first medication for obstructive sleep apnea. Published December 20, 2024. Accessed January 4, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea
12. Malhotra A, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. *N Engl J Med.* 2024. doi:10.1056/NEJMoa2404881
13. Bliddal H, et al. Semaglutide treatment in patients with obesity and knee osteoarthritis. *N Engl J Med.* 2024. doi:10.1056/NEJMoa2403664
14. Hendershot CS, et al. Once-weekly semaglutide in adults with alcohol use disorder. *JAMA Psychiatry.* 2025.
15. Athauda D, et al. Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. *Lancet.* 2017;390(10103):1664-1675.
16. Sanyal AJ, et al. Phase 3 trial of semaglutide in metabolic dysfunction–associated steatohepatitis. *N Engl J Med.* 2025.
17. American Society for Metabolic and Bariatric Surgery. Bariatric surgery more effective and durable than new obesity drugs and lifestyle intervention. Published June 13, 2024. Accessed January 4, 2026. https://asmbs.org/news_releases/bariatric-surgery-more-effective-and-durable-than-new-obesity-drugs-and-lifestyle-intervention/
18. Wegovy (semaglutide) tablets prescribing information. U.S. Food and Drug Administration. 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218316Orig1s000lbl.pdf
19. NovoCare (Novo Nordisk). Wegovy cost & coverage information (NovoCare Pharmacy self-pay pricing). Accessed January 4, 2026. https://www.novocare.com/patient/medicines/wegovy.html
20. Eli Lilly and Company. Savings Options | Zepbound® (tirzepatide). Accessed January 4, 2026. https://zepbound.lilly.com/savings
21. NovoPricing (Novo Nordisk). Wegovy pricing (WAC). Accessed January 4, 2026. https://www.novopricing.com/wegovy.html
22. Endotext. Pharmacologic treatment of overweight and obesity in adults. *NCBI Bookshelf.* Accessed January 4, 2026. https://www.ncbi.nlm.nih.gov/books/NBK279038/
23. Mauer Y, Parker M, Kashyap SR. Antiobesity drug therapy: an individualized and comprehensive approach. Cleve Clin J Med. 2021;88(8):440-448. doi:10.3949/ccjm.88a.20080
24. GoodRx. Metformin prices. Accessed January 4, 2026. https://www.goodrx.com/metformin
25. GoodRx. Bupropion prices. Accessed January 4, 2026. https://www.goodrx.com/bupropion
26. GoodRx. Topiramate prices. Accessed January 4, 2026. https://www.goodrx.com/topiramate
27. GoodRx. Naltrexone prices. Accessed January 4, 2026. https://www.goodrx.com/naltrexone
28. GoodRx. Alli (orlistat 60 mg) prices. Accessed January 4, 2026. https://www.goodrx.com/alli
29. GoodRx. Contrave prices. Accessed January 4, 2026. https://www.goodrx.com/contrave
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