A little, and triglycerides fall much more than LDL. In the 68-week STEP 1 trial of semaglutide 2.4 mg, LDL cholesterol fell 2.5 percent from an average of 110.3 mg/dL, roughly 3 mg/dL [1] [2]. On placebo it rose 1.3 percent. Triglycerides fell 21.9 percent against 7.3 percent. At the lower Ozempic doses, a network meta-analysis of 76 diabetes trials put the LDL reduction at 0.16 mmol/L [3].
Two cautions apply to every number below. First, the Ozempic label itself prints no cholesterol table; the trial percentages come from Wegovy, the 2.4 mg dose of the same drug. Second, lipids were secondary measures in these trials. How the two drugs compare on weight, the primary outcome, is in tirzepatide against semaglutide.
What STEP 1 measured on cholesterol
STEP 1 randomized 1,961 adults with obesity or overweight and no diabetes, 2:1, to semaglutide 2.4 mg or placebo for 68 weeks [2]. The label reports the lipid results as percent change from baseline [1]:
- Total cholesterol: −3.3 percent against +0.1 percent, from 189.6 mg/dL.
- LDL cholesterol: −2.5 percent against +1.3 percent, a relative difference of −3.8 percent.
- HDL cholesterol: +5.2 percent against +1.4 percent.
- Triglycerides: −21.9 percent against −7.3 percent, from 126.2 mg/dL.
The label notes that these measures were not part of the pre-specified testing order. The LDL change is small next to the triglyceride change. A pooled analysis of four 2.4 mg trials of at least 68 weeks gives the same shape in mg/dL [4]. LDL fell by a mean 6.01 mg/dL, total cholesterol by 6.39 mg/dL and triglycerides by 14.75 mg/dL. HDL rose by 1.82 mg/dL.
Does Ozempic lower cholesterol in type 2 diabetes?
Ozempic is approved for type 2 diabetes at 0.5 to 2 mg. The best estimate for that population is a network meta-analysis of 76 trials, 15 GLP-1 drugs and 39,246 adults [3]. Against placebo, the mean difference for semaglutide was −0.16 mmol/L for LDL (95% CI −0.30 to −0.02). For total cholesterol it was −0.48 mmol/L (95% CI −0.84 to −0.11). The LDL interval ends just short of zero.
One trial in the Wegovy label shows the limit directly. In STEP 2, adults with type 2 diabetes on 2.4 mg saw LDL change by +0.5 percent against +0.1 percent on placebo [1]. Triglycerides still fell, by 22 percent against 9.4 percent. In that trial, the triglyceride effect held and the LDL effect did not appear.
Does Zepbound lower cholesterol?
Tirzepatide moved lipids further in its obesity trial. The Zepbound label reports 72-week results from SURMOUNT-1 by dose [5]. LDL fell 4.6, 5.6 and 7.1 percent on 5, 10 and 15 mg, against 1.7 percent on placebo, from about 109 mg/dL. The relative difference at 5 mg had a confidence interval crossing zero. Triglycerides fell 21.2 to 29.1 percent against 5.6 percent, and HDL rose 6.9 to 9.2 percent.
A meta-analysis of seven randomized trials found the same pattern with dose [6]. Total cholesterol fell 3.76 percent on 5 mg, 4.63 percent on 10 mg and 5.93 percent on 15 mg. LDL and triglycerides fell and HDL rose. How much of this follows weight loss rather than the drug itself was not separated in these abstracts. A SURMOUNT-1 analysis of uric acid faced the same question, set out in the uric acid log entry.
Cholesterol medicines and heart risk
One pooled analysis looked at lipid-lowering prescriptions across five STEP trials [7]. More people on semaglutide had their lipid-lowering treatment reduced, and fewer had it intensified, than on placebo. The abstract gives no counts. It is a post hoc analysis, and several authors are Novo Nordisk employees.
In SELECT, 17,604 adults with established cardiovascular disease and no diabetes took semaglutide 2.4 mg or placebo [1]. At baseline, 90 percent were on lipid-lowering therapy. At week 104, LDL changed −5.3 percent against −3.1 percent, from 78.5 mg/dL. The trial was built to measure a composite of cardiovascular death, heart attack and stroke, and the cholesterol change beside it was small. What drove the benefit is covered in whether GLP-1 drugs prevent heart attacks and strokes and in the inflammation evidence.