What is semaglutide used for?

What it is being studied for

• Weight in adults with obesity: 14.9% average loss vs 2.4% on placebo over 68 weeks in 1,961 adults (STEP 1), a human randomized trial [1].
• Heart events in obesity without diabetes: 6.5% vs 8.0% had a heart attack, stroke or cardiovascular death (HR 0.80) over a mean 39.8 months in 17,604 people (SELECT), a human randomized trial [2].
• Heart events in type 2 diabetes: 6.6% vs 8.9% (HR 0.74) over 104 weeks in 3,297 patients (SUSTAIN-6), a human randomized trial [3].
• Kidney disease in type 2 diabetes: fewer major kidney events (HR 0.76) over a median 3.4 years in 3,533 patients (FLOW, stopped early), a human randomized trial [4].
• Heart failure with preserved ejection fraction and obesity: symptom score up 16.6 vs 8.7 points and weight down 13.3% vs 2.6% at 52 weeks in 529 patients (STEP-HFpEF), a human randomized trial [5].
• Knee osteoarthritis with obesity: pain score down 41.7 vs 27.5 points at 68 weeks in 407 people (STEP 9), a human randomized trial [6].
• Fatty-liver disease with inflammation and fibrosis (MASH): inflammation resolved in 62.9% vs 34.3% and fibrosis improved in 36.8% vs 22.4% at 72 weeks, an interim analysis of a human randomized trial (ESSENCE) [7].
• Adolescents with obesity: BMI down 16.1% vs up 0.6% over 68 weeks in 201 teenagers (STEP TEENS), a human randomized trial [8].
• Tablet form for obesity: 15.1% vs 2.4% weight loss with a 50 mg daily tablet over 68 weeks in 667 adults (OASIS 1), a human randomized trial [9].
• Early Alzheimer’s disease: no difference on a dementia rating score at 104 weeks (−0.08, p=0.57; 0.10, p=0.46) in 3,808 people, two human randomized trials (evoke, evoke+) that were stopped for a negative result [10].

How it works

1. It is a modified copy of the human gut hormone GLP-1 with two amino-acid swaps; in laboratory tests it bound the GLP-1 receptor at 0.38 nM [11].
2. A fatty-acid chain attached to the peptide makes it stick to albumin in the blood and resist breakdown: the half-life was 46.1 hours in mini-pigs [11] and is about one week in people [3].
3. In STEP 1 the weight loss came with improvements in cardiometabolic risk factors [1], and a separate human trial was designed to measure its effect on energy intake, appetite and stomach emptying [12]; how the heart and kidney benefits arise is not established in these trials.
4. What sets it apart from GLP-1 itself is that side chain and the two swaps, which the developers built for once-weekly dosing [11]; it has also been tested as a daily tablet [9].

Adverse events reported

• Nausea and diarrhoea were the most common effects, mostly mild to moderate and transient; 4.5% vs 0.8% stopped for stomach and gut effects (STEP 1) [1].
• 16.6% vs 8.2% stopped permanently because of adverse events (SELECT) [2].
• Diabetic eye (retinopathy) complications were more frequent (HR 1.76), alongside fewer serious adverse events overall (SUSTAIN-6) [3].
• Serious adverse events were lower than placebo in FLOW (49.6% vs 53.8%) [4] and STEP-HFpEF (13.3% vs 26.7%) [5].
• 6.7% vs 3.0% stopped for adverse events, mostly stomach and gut effects (STEP 9) [6].
• Stomach and gut effects were more common in ESSENCE [7] and STEP TEENS (62% vs 42%), where gallstones occurred in 4% vs 0 [8].
• Adverse events were reported in 91.2% vs 84.8% in the Alzheimer’s trials [10].

Forms

Human trials tested a once-weekly injection under the skin [1][3] and a once-daily tablet, at 50 mg for weight [9] and up to 14 mg in the Alzheimer’s trials [10]. Under-the-tongue and nasal forms have no human trial in the sources reviewed here.

How the tablet and the injection compare, with the trials behind each: Semaglutide pills vs injection.