Where lipid results sit in a label
Cholesterol and triglycerides are not the reason these medicines are prescribed. They appear in section 14 of the weight-management labels, in tables of cardiometabolic measures recorded alongside body weight. The figures are average percentage changes from the start of the trial, and the starting values are given as geometric means, a type of average suited to measures that vary widely between people.
The labels also mark these results as outside their main statistical testing: Wegovy® says they were not part of the pre-specified hierarchy, and Zepbound® and Foundayo™ say they were not controlled for the risk of chance findings [1][2][4]. They describe what happened in the trials rather than establish a lipid-lowering effect.
What a lipid panel measures
MedlinePlus describes the standard lipid panel. LDL is the cholesterol most linked with build-up in the arteries; HDL helps carry cholesterol away from them; non-HDL is total cholesterol minus HDL and covers all the types linked to heart risk; triglycerides are a separate blood fat measured in the same test [11]. It adds that the right numbers for you depend on your age, blood pressure, family history and other factors, which is a conversation for your clinician.
Why the Mounjaro label has no lipid table
Mounjaro® is approved in the US for type 2 diabetes, and its clinical studies section reports blood sugar and cardiovascular outcomes, not cholesterol. In its heart outcomes trial, 86% of participants were already on a statin, and doctors were expected to manage lipids and blood pressure to local standards, which is a different thing from measuring an effect of the medicine [5].
The lipid figures for tirzepatide in the US therefore come from the Zepbound® label. In Europe, where Mounjaro® is also authorised for weight management, the European Medicines Agency’s public summary says it improved blood pressure and the amount of fat in the blood, without giving figures [7]. The full European product information does give figures, set out below [6].
The numbers, trial by trial
Percentage change from the start of each trial to its end, from section 14 of each US label. Ranges cover the dose groups; the Saxenda® triglyceride figures are medians.
| Label and trial | LDL: placebo | LDL: medicine | Triglycerides: placebo | Triglycerides: medicine |
|---|---|---|---|---|
| Zepbound®: SURMOUNT-1, 72 weeks [1] | −1.7 | −4.6 to −7.1 | −5.6 | −21.2 to −29.1 |
| Zepbound®: Study 2, type 2 diabetes, 72 weeks [1] | +7.4 | +1.8 to +4.1 | −3.3 | −27.1 to −27.3 |
| Wegovy® 2.4 mg: STEP 1, 68 weeks [2] | +1.3 | −2.5 | −7.3 | −21.9 |
| Wegovy® 2.4 mg: Study 3, type 2 diabetes, 68 weeks [2] | +0.1 | +0.5 | −9.4 | −22.0 |
| Wegovy® 7.2 mg: Study 8, 72 weeks [2] | −4.8 | −3.5 | −0.9 | −16.4 |
| Wegovy® 25 mg tablets: Study 7, 64 weeks [2] | +0.2 | −2.9 | −9.1 | −18.1 |
| Wegovy® 2.4 mg: SELECT, week 104 [2] | −3.1 | −5.3 | −3.2 | −18.3 |
| Saxenda®: Study 1, 56 weeks [3] | −0.7 | −3.1 | −4.1 | −13.0 |
| Saxenda®: Study 2, type 2 diabetes, 56 weeks [3] | +3.3 | +0.9 | −0.7 | −14.5 |
| Foundayo™: Trial 1, 72 weeks [4] | −1.6 | −3.8 to −5.5 | −4.0 | −10.4 to −20.0 |
| Foundayo™: Trial 2, type 2 diabetes, 72 weeks [4] | −3.1 | −0.2 to −5.5 | −4.1 | −13.3 to −19.4 |
HDL and total cholesterol
HDL, often called the good cholesterol, rose a little in almost every one of these trials: by 6.9% to 9.2% with Zepbound® against a 0.7% fall on placebo, 5.2% with Wegovy® in STEP 1 against 1.4%, 9.5% with the 7.2 mg dose against a 0.5% fall, 2.3% with Saxenda® against 0.5%, and 2.1% to 4.5% with Foundayo™ against a 1.0% fall [1][2][3][4]. Total cholesterol fell by a few percent in most cases.
The pattern is consistent across molecules: the largest movement is in triglycerides, LDL changes by a few percent at most, and HDL edges up. In the Zepbound® trial of people with type 2 diabetes, LDL actually rose slightly in every group, including placebo, and in the 7.2 mg Wegovy® trial LDL fell slightly less than on placebo, which shows how small and variable the LDL effect is [1][2].
Mounjaro® in the European product information
- Across the SURPASS diabetes trials, triglycerides fell by 15% to 19% on 5 mg, 18% to 27% on 10 mg and 21% to 25% on 15 mg [6].
- In the 40-week trial against semaglutide 1 mg, triglycerides fell 19%, 24% and 25% on the three tirzepatide doses, against 12% on semaglutide [6].
- In SURPASS-CVOT, triglycerides were 27% lower at month 24 on tirzepatide, against 11% on dulaglutide [6].
- In SURMOUNT-1, the pooled tirzepatide doses changed triglycerides by −27.6% against −6.3% on placebo, non-HDL cholesterol by −11.3% against −1.8%, and HDL by +7.9% against +0.3% [6].
What changed in the lab, not just in weight
Some documents describe short pharmacology studies of fat in the blood. In the European Ozempic® information, semaglutide 1 mg lowered fasting triglycerides by 12% and VLDL cholesterol by 21% against placebo, and the rise in both after a high-fat meal was more than 40% smaller [8]. The European information for semaglutide tablets reports 19% and 20% lower fasting values and a 24% and 21% smaller rise after a high-fat meal [9].
These studies were short and small and cannot separate the medicine’s own effect from eating less. The US labels themselves do not explain the mechanism of the lipid changes.
When treatment stops
Two US labels include withdrawal trials in which people who had responded were randomly switched to placebo. In the Wegovy® study known as STEP 4, from the switch at week 20 to week 68, LDL rose 7.6% on placebo against 1.1% on continued treatment, and triglycerides rose 14.8% against a 5.6% fall [2]. In the Zepbound® withdrawal study, SURMOUNT-4, LDL and triglycerides ended 6.5% and 16.1% lower with continued treatment than with placebo [1].
A year after STEP 1 ended, with no treatment at all, its extension study reported that most cardiometabolic improvements had drifted back towards their starting values [10]. Any decision about stopping or continuing is for your prescriber.
What these averages do not tell you
The trials ran alongside a reduced-calorie diet and more physical activity, and participants lost a substantial amount of weight. The labels do not separate the effect of the medicine from the effect of that weight loss. The National Heart, Lung, and Blood Institute notes that losing even a few percent of body weight can lower triglycerides, and somewhat more can lower LDL and raise HDL [12]. The figures are averages, and individual results vary in both directions.
Many participants were already on cholesterol treatment. In SELECT, 90% were taking lipid-lowering therapy at the start, and investigators could adjust it during the trial [2]; in the semaglutide tablet heart trial the figure was 89% [9]. None of these labels lists high cholesterol among its approved uses, and none suggests that a GLP-1 can stand in for a statin or other prescribed lipid medicine.
Statins and these medicines
The Foundayo™ label has a specific interaction with a cholesterol medicine. Orforglipron roughly doubled exposure to the active form of simvastatin, so the label sets an upper limit of 20 mg a day on simvastatin taken with it. Atorvastatin and rosuvastatin levels also rose, but the label does not regard those changes as clinically relevant [4].
For the semaglutide tablets, the European product information reports a 41% rise in rosuvastatin exposure that it does not consider clinically relevant [9]. For liraglutide, the Saxenda® label lists atorvastatin among the tested medicines: its peak was lower, but the label found no clinically relevant change in absorption [3]. If you take a statin, make sure your prescriber and pharmacist know about your GLP-1.
Teenagers in the trials
The labels also report lipids in their adolescent trials. In the Wegovy® trial of 12- to 17-year-olds, LDL fell 9.9% against 3.6% on placebo and triglycerides 28.4% against a 2.6% rise [2]. In the Saxenda® adolescent trial, LDL rose slightly in both groups, by 1.7% against 3.0% [3]. Neither medicine is approved for cholesterol in young people.
Mounjaro®, Zepbound® and Foundayo™ are trademarks of Eli Lilly and Company. Wegovy®, Ozempic® and Saxenda® are registered trademarks of Novo Nordisk A/S. PepLabo is not affiliated with or endorsed by Eli Lilly and Company or Novo Nordisk.
