The GLP-1 Starter Guide

The four molecules in plain English

Four drugs come up in almost every GLP-1 conversation. Here is what they actually are.

• Tirzepatide (sold as Mounjaro for type 2 diabetes, Zepbound for weight loss) - a dual GLP-1 + GIP agonist, meaning it mimics two of your gut hormones at once instead of one. Strongest weight loss results in head-to-head trials to date. FDA-approved 2022 (Mounjaro) and 2023 (Zepbound).
• Semaglutide (sold as Ozempic for diabetes, Wegovy for weight loss, Rybelsus as a daily oral pill for diabetes) - a GLP-1 agonist that mimics one gut hormone. Largest real-world track record. FDA-approved 2017 (Ozempic) and 2021 (Wegovy). The SELECT cardiovascular outcomes trial in 2023 showed a 20% reduction in major heart events for adults with overweight and existing cardiovascular disease.
• Retatrutide (no brand name yet) - a triple-agonist targeting GLP-1, GIP, and glucagon. Phase-3 trials still running. FDA submission expected 2026-2027. Not commercially available.
• Liraglutide (Saxenda for weight loss, Victoza for diabetes) - an older GLP-1 that requires daily injections rather than weekly. Generally outperformed by semaglutide and tirzepatide in newer trials. Rarely the first recommendation now.

The choice your telehealth provider will frame for you

Most telehealth services offer either tirzepatide or semaglutide. The conversation almost always comes down to two forks.

Brand-name vs. compounded. Brand-name drugs (Mounjaro, Zepbound, Ozempic, Wegovy) are FDA-regulated, well-studied, and expensive - typically $800 to $1,300 per month without insurance. Compounded versions are made by compounding pharmacies (state-licensed facilities that mix medications to order) and cost $200 to $500 per month. Compounded GLP-1s are legal in more complex ways that vary by state and changed when the FDA's shortage declarations shifted in 2024 and 2025. Quality also varies by pharmacy. Your provider should know which pharmacies they trust.

Tirzepatide vs. semaglutide. Tirzepatide tends to produce larger average weight loss. Semaglutide has more cardiovascular outcomes data and a longer track record. If you have a history of heart disease, ask specifically about semaglutide first - the SELECT trial data matters here. If you don't have cardiovascular disease, the choice is often about your doctor's preference, your insurance coverage, and your access to reliable compounding.

Cost paths in 2026

• Insurance covers brand-name (Wegovy or Zepbound) - usually requires a BMI of 30 or higher for the obesity indication, or BMI 27 or higher with a comorbidity (a separate condition like high blood pressure or sleep apnea that accompanies the weight). Cost with approval: $25 to $100 per month copay. Requires a letter from your doctor and often a prior-authorization process.
• Insurance covers diabetes-indicated brand (Mounjaro, Ozempic) - requires a type 2 diabetes diagnosis. Some practices prescribe off-label for weight loss, but coverage is harder to get without the diagnosis on record.
• Telehealth with compounded peptide - $200 to $500 per month out of pocket. Eden Health, SkinnyRx, Yucca Health, and Fridays Health are common providers in 2026. Their specific formularies and pricing shift quarterly - check their current tirzepatide vs. semaglutide options before committing.
• Skip entirely - Instagram-sourced peptides without a prescription, unverified telehealth services that don't provide a real prescription, and group buys from research vendors. None of these.

What to ask your telehealth provider on the call

• Ask which compounding pharmacy they use, and request to see the COA (Certificate of Analysis - the lab report verifying the purity and concentration of the batch you'll receive) for your specific order. No COA means no quality control.
• Confirm the dosing ramp. Standard tirzepatide protocol starts at 2.5mg and increases every four weeks if you're tolerating it, up to a max of 10 to 15mg for weight loss. Some providers push faster ramps. Slower ramps mean fewer side effects at each step up.
• Ask about their side-effect management plan. Nausea hits 40 to 60% of users in clinical trials, especially at dose increases. Ask whether they co-prescribe an anti-nausea medication like ondansetron (brand name Zofran) or have a protocol for managing it. A provider who says "nausea isn't a problem" hasn't done many of these.
• Confirm the no-go list. History of medullary thyroid cancer, MEN-2 (a rare endocrine syndrome affecting multiple glands), pancreatitis, or severe gastroparesis (a condition where the stomach empties too slowly) are all reasons a provider should not prescribe GLP-1 agonists. Make sure they ask about these.
• Ask about the discontinuation plan. Most of the weight lost returns within 12 months of stopping. This is not a 6-month course - it is a long-term medication for most people. Know that going in.

What to expect in the first 8 weeks

• Weeks 1-2 - starting dose (2.5mg tirzepatide, or equivalent semaglutide ramp). Nausea is common. Weight loss is small, typically 1 to 3 pounds. Some people feel nothing; some feel it significantly.
• Weeks 3-4 - nausea usually improves as your body adjusts. Weight loss picks up. Most people hit their first real number here.
• Weeks 5-8 - dose increases to 5mg around week four. The nausea often comes back at the dose bump, then settles again. Weight loss runs roughly 1 to 2 pounds per week at this stage for most people.
• At 8 weeks - most users are 8 to 15 pounds down. If you've lost fewer than 4 pounds, ask your provider about a different molecule, a faster ramp, or whether something else is going on.

Subscribe to the dispatch

The weekly Protocol One dispatch covers what's moving in peptides, GLP-1s, and longevity protocols. Broken down for normal humans.

Subscribe free