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The benefits and trade-offs of GLP-1 medications, with the trial behind each one.

Ozempic, Wegovy, Mounjaro and Zepbound produced large average weight loss in trials, and they come with side effects, costs and open questions. Here is what the evidence shows on both sides.

See the benefits See the trade-offs

What the trials show
reaches beyond the scale.

In large trials, GLP-1 medications lowered weight, blood sugar and cardiovascular events, and some of those changes appeared before much weight was lost.

  • Weight loss

    Semaglutide 2.4 mg (Wegovy) produced an average loss of about 15% of body weight over 68 weeks in STEP 1, and tirzepatide (Zepbound), which acts on both the GLP-1 and GIP receptors, about 21% at the highest dose over 72 weeks in SURMOUNT-1.1,2 For a 250-pound person, 15–21% is about 38–52 pounds.

  • Heart outcomes

    In the SELECT trial, semaglutide reduced major adverse cardiovascular events by 20% in adults with overweight or obesity and existing cardiovascular disease who did not have diabetes.3 The benefit appeared early, before most weight was lost, which suggests mechanisms beyond weight loss, possibly including effects on inflammation.

  • Blood sugar and insulin sensitivity

    GLP-1 medicines were first developed for type 2 diabetes. In people with type 2 diabetes they lower HbA1c, typically by about 1.0–2.5 percentage points, and reduce insulin resistance. In people without diabetes, better insulin sensitivity is linked with a lower chance of progressing to type 2 diabetes.

  • Inflammation markers

    GLP-1 medicines most consistently lower hs-CRP, a common blood marker of inflammation, with smaller and less consistent effects on cytokines such as IL-6 and TNF-α.4 In SELECT, hs-CRP fell before major weight loss and even in participants who did not lose weight, so the effect appears to be partly independent of weight loss. How it happens is still being studied.

  • Appetite

    These medicines mimic a gut hormone that signals fullness to the brain. They slow stomach emptying and reduce hunger, and many people describe less “food noise”, the constant background preoccupation with eating.

  • Brain health, still an open question

    Researchers continue to study GLP-1 receptors in neurodegenerative disease. The EVOKE and EVOKE+ trials of oral semaglutide in early Alzheimer’s disease found no clinical benefit after two years, despite lowering hs-CRP, a reminder that a change in a blood marker doesn’t guarantee a clinical outcome.6 Research in other neurological diseases is ongoing.

What to weigh
before and during treatment.

No medication is risk-free. These are the side effects and practical issues reported most often, and the ones to discuss with your prescriber.

  • Stomach and gut side effects

    These are the most common side effects and the most common reason people stop GLP-1 therapy because of side effects. Nausea affects roughly 30–45% of participants, mostly while the dose is being raised, and diarrhea (about 20–30%), vomiting (about 10–25%) and constipation (about 10–25%) are also common.1,2 For most people they ease over weeks; for a minority they stay severe enough to need a lower dose or stopping.

  • Lean mass loss

    In trial body-composition substudies, roughly 25–40% of the weight lost on semaglutide and tirzepatide was lean mass rather than fat; lean mass includes muscle along with water and organ tissue.1,2 Some lean loss comes with any large weight loss, and a smaller appetite can make eating enough protein harder. It matters most in older adults, for whom muscle loss is already a concern. Blood labs don’t measure it; body-composition scans such as DXA do.

  • Thyroid warning

    Semaglutide and tirzepatide carry an FDA boxed warning, the most serious type of drug safety warning, about thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), based on rodent studies. Whether this applies to people is uncertain, because rodent thyroid biology differs, but the medicines are not used in people with a personal or family history of MTC or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). The labels describe routine calcitonin or thyroid ultrasound monitoring as of uncertain value, and TSH doesn’t screen for C-cell tumors.

  • Gallbladder and pancreas

    Rapid weight loss from any cause raises the chance of gallstones. In STEP 1, gallbladder-related events occurred in 2.6% of participants on semaglutide versus 1.2% on placebo, mostly gallstones.1 Acute pancreatitis is rare (under 0.5% in trials) but serious, and people with a history of pancreatitis should discuss it with their prescriber before starting.

  • Weight regain after stopping

    In the STEP 1 extension, participants who stopped semaglutide regained about two-thirds of the weight they had lost within a year.5 Because much of the weight and some metabolic changes return after stopping, many clinicians treat these medicines as long-term, much like blood pressure medication.

  • Cost and coverage

    Without insurance, GLP-1 medications are a significant monthly expense, even with manufacturer self-pay programs. Coverage is expanding, but many plans still exclude weight-loss medications or require prior authorization with BMI thresholds and documented attempts at lifestyle change. Some people turn to compounded versions of uncertain quality, or go on and off the medicine because of cost.

Different questions
call for different measurements.

Some of the trade-offs above can be followed with scans and routine labs your prescriber orders. The Inflammation Compass measures something those don’t reach.

  • Lean mass

    Body-composition scans such as DXA measure lean mass directly. Blood tests, including the Inflammation Compass, don’t.

  • Liver, blood sugar and lipids

    Your prescriber may order liver enzymes (ALT, AST), A1C, lipids and kidney function before and during treatment.

  • Inflammation

    hs-CRP measures one protein. The Inflammation Compass reads which genes your immune cells are using and reports six readings, three for the signals that start a response and three for the signals that end it. Across samples, it shows which parts of your inflammation system moved and by how much.

  • Plateaus

    Why weight loss levels off, how often trial participants lost less than 5%, and questions to take to your prescriber.

The Inflammation Compass shows what changed, not why, and doesn’t show whether a medication is working or safe. What a change means is for you and your prescriber to weigh.

Read more

  • When weight loss slows or stalls

    Plateaus and non-response, the factors researchers have looked at, and questions to take to your prescriber.

  • GLP-1 and inflammation

    What the trials show about GLP-1 medicines and inflammation, and what the six readings show across your samples.

  • What RNA adds

    How reading which genes your immune cells are using differs from a routine blood test.

See what changes in your inflammation while you're on GLP-1 therapy.

The Inflammation Compass adds a read of your immune cells' gene activity to the labs and scans your prescriber uses.

Reserve your spot GLP-1 and inflammation
Sources and further reading

References

1. Wilding JPH, et al. (2021) — Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 384(11):989–1002. doi:10.1056/NEJMoa2032183. PMID 33567185.
2. Jastreboff AM, et al. (2022) — Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med. 387(3):205–216. doi:10.1056/NEJMoa2206038. PMID 35658024.
3. Lincoff AM, et al. (2023) — Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). N Engl J Med. 389(24):2221–2232. doi:10.1056/NEJMoa2307563. PMID 37952131.
4. Plutzky J, et al. (2026) — Effect of semaglutide on the inflammatory biomarker high-sensitivity CRP in patients with established cardiovascular disease and overweight or obesity in SELECT: a prespecified secondary analysis. Circulation. 154(11):976–991. doi:10.1161/CIRCULATIONAHA.125.074482. PMID 42610271.
5. Wilding JPH, et al. (2022) — Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab. 24(8):1553–1564. doi:10.1111/dom.14725. PMID 35441470.
6. Cummings JL, Scheltens P. (2026) — Evoke (+) trials of semaglutide for early Alzheimer's disease: innovations, lessons, and implications. J Prev Alzheimers Dis. 13(10):100677. doi:10.1016/j.tjpad.2026.100677. PMID 42785112.