Semaglutide
Ozempic / WegovyNovo Nordisk • ~14.9% at 68 weeks in STEP-1 (obesity, no diabetes).
Pure GLP-1 agonist that set the modern baseline for weight loss and CV benefit. First GLP-1 to show hard CV benefit in people with obesity but no diabetes (SELECT).
Who might choose this drug?
- ✓You have heart disease or high CV risk and want proven cardiovascular protection
- ✓You have (or are at risk for) MASH/fatty liver disease and want FDA-approved liver treatment
- ✓You have chronic kidney disease with diabetes and need kidney protection
- ✓You prefer a medication with the longest real-world safety data and widest clinical experience
- ✓You want a single-hormone approach that's been extensively studied
Health Outcomes Beyond Weight
- •SELECT trial: 20% reduction in major adverse cardiovascular events (MACE)
- •Studied in 17,604 adults with obesity and established CVD, no diabetes
- •FDA approved Wegovy to reduce risk of heart attack and stroke in high-risk patients
- •Benefits appear independent of weight loss magnitude
- •STEP-HFpEF: Significant improvements in HFpEF symptoms and physical function
- •+20 meter improvement in six-minute walk distance
- •Reduced inflammation markers and improved quality of life
- •EMA endorsed Wegovy for obesity-related HFpEF
- •FLOW trial: First dedicated kidney outcomes trial for GLP-1 RA in T2D + CKD
- •Reduced kidney failure, >50% eGFR decline, and CV death
- •FDA approved Ozempic to reduce risk of kidney disease progression
- •Benefits seen across range of baseline kidney function
- •ESSENCE trial: 63% achieved MASH resolution without fibrosis worsening
- •~37% showed improvement in fibrosis stage
- •August 2025: FDA accelerated approval for MASH with moderate-to-advanced fibrosis
- •First GLP-1 class drug approved for liver disease treatment
- •STEP 9: Patients with obesity and knee OA had greater pain reduction vs placebo
- •Studied over 68 weeks in people with BMI ≥30
- •Mechanisms: Both mechanical load reduction and direct anti-inflammatory effects
- •May be disease-modifying for obesity-related OA
- •Consistent reductions in hsCRP (high-sensitivity C-reactive protein)
- •Decreased IL-6, TNF-α, and other inflammatory markers
- •Improvements in endothelial function and oxidative stress
- •Inflammation reduction likely mediates many cardiometabolic benefits
SELECT: ~20% reduction in major CV events (CV death, MI, stroke) in adults with obesity and established CVD, no diabetes.
STEP-HFpEF: symptom improvements and +20m six-minute walk distance in obesity-related heart failure with preserved ejection fraction.
FLOW: kidney and CV protection in T2D with chronic kidney disease.
ESSENCE: histologic improvements in metabolic dysfunction-associated steatohepatitis (MASH).
Long-term data show weight and CV benefit can persist for several years if treatment is continued; stopping tends to be followed by partial weight regain.
Still Being Studied
- Long-term safety beyond ~5 years in very large real-world populations.
- Best strategies to prevent weight regain if treatment is stopped.
- Optimal use in diverse populations and special circumstances (pregnancy, adolescents, older adults).