Any experience with Nexletol or Nexlezet?

It took me months to understand what caused what, but finally understood that a mix of causes included Repatha in a major way. Also if you are taking 2 monoclonal antibodies like I was, is there any science that tells us how that works?

Nexletol is working for me! My total cholesterol is barely above 200, HDL and LDL are “pretty good”. I’ve just started started taking pravastatin with Nexletol. Considering how sick from Repatha and from other statins (other than low doses of pravastatin), I’m very happy! Nexletol is expensive, but no more than one ER out of pocket.

Same here. Statins and Praluent are out for me. I am now on Nexletol and Zetia. It is helping. I have LP(a). My Dr wants my LDL to be below 30. It's 55. It was 120. I don't seem to have any side effects. I also take Benacol a stanol supplement in a chocolate chew. Dr Dayspring says to attack the receptors in the liver and intestines. If you do one or the other, the organ that is not medicated, will put out more receptors.

What were your Praluent side effects? My second dose I had tingly lips and tongue, like it was an allergic reaction.

Best wishes.

Thanks for your post. With Praluent I experienced extreme fatigue. I went to urgent care thinking something was seriously wrong. Given the long half life of the medication it took about 8 weeks to recover. I’m going to start Nexletol this week.

I hope it works well for you!

Was placed on nexlizet, developed gout, unable to urinate, cramps in leg , issues resolved after the med stopped. Never had any of these issues before taking this med. Be very careful.

Interesting question, @tatiana987. You may have mentioned the other monoclonal antibody drug you are taking but I am not seeing it.

What else are you taking besides Repatha? Did you start them at the same time?

I have taken Prolia for osteoporosis for nearly 10 years, I had some reactions to the shots in the beginning (injections were every 6 months). For about 3 years, I used Benedryl for that. Then I seemed to adjust and used the Prolia without Benedryl until the present time. For the most recent shot I had about a week of light headedness and minor nausea,

I began Repatha September 29, 2024, took 17 injections on a 2 week schedule. I didn’t make the connection to my problems with light headedness and falling until my neurologist took my drivers license away and I was in a horrible panic and unable to continue my normal, healthy life style. I tried to turn myself into a scientist and reviewed all medical records, as well as my own records. I figured out my problem by talking to Amgen, the manufacturer of both monoclonal antibodies and by using Dr. Google, where I found thus group,

Sad thing is that both Prolia and Repatha did what they were supposed to do. My labs and dexa scans were lots better.

I've become hypersensitive to statins. I can't even take low doses for more than 3 weeks without having muscle, joint, and stiffness issues. I've been taking Zetia. It seems to do little or nothing. I added Nexletol 6 mos ago. My lipid blood test was terrible. Almost as if I was taking nothing. I have no symptoms either. I'm dispirit to find out why. Has anyone run into this?

@jahman57 Why Zetia + Nexletol may appear to be doing “nothing”.

What you are describing does happen, and there are several plausible explanations—often more than one at the same time.

1. These drugs lower LDL less than statins.
Zetia (ezetimibe) typically lowers LDL by ~15–25%.
Nexletol (bempedoic acid) lowers LDL by ~15–20%.
Together, the average LDL reduction is ~30–35%.

If someone:
Started with very high LDL, or
Previously had large LDL reductions on statins
…the change can feel disappointing or negligible, even though the drugs are working within their expected range.

2. Underlying genetic cholesterol disorders.
If LDL remains very high despite therapy, possibilities include:

Familial hypercholesterolemia (FH) (even milder or late-diagnosed forms).
Other inherited lipid metabolism issues.

In these cases:
Oral medications often cannot overcome the genetic signal
Injectable therapies may be needed (see below).

3. Absorption or metabolic variability:

Some people:
Absorb less ezetimibe from the gut
Metabolize bempedoic acid differently
Have liver pathways that respond weakly to these mechanisms.
This is not rare and usually not detectable without trial-and-error treatment.

4. Secondary causes raising cholesterol:

Even if medications are correct, LDL may stay high if something else is driving it, such as:

Hypothyroidism.
Insulin resistance or diabetes.
Chronic kidney disease.
High saturated-fat intake.
Certain medications (steroids, some psych meds, etc.).
If these aren’t addressed, lipid drugs can look ineffective.

5. Statin intolerance is real—but often complex.
True statin intolerance does occur, especially:

Muscle pain, stiffness, weakness
Symptoms returning consistently with re-challenge.

However, some patients tolerate:

Very low-dose statins (e.g., once or twice weekly).
Hydrophilic statins (pravastatin, rosuvastatin) better than others.
That said, if symptoms are reproducible, forcing statins is not appropriate.
What usually works when this happens:

If LDL remains high despite Zetia + Nexletol, guidelines typically move to PCSK9 therapy, such as:

Repatha (evolocumab).
Praluent (alirocumab).

These:
Lower LDL by 50–60%.
Are not statins.
Rarely cause muscle symptoms.
Work well in statin-intolerant patients.
Some people also benefit from:
Inclisiran (twice-yearly injection).
Combination therapy tailored to genetics and risk.
Why they may feel “no symptoms”:

That part is actually expected:
High cholesterol does not cause symptoms.
Muscle pain comes from medications, not cholesterol itself.
Cardiovascular risk accumulates silently over years.
So feeling fine does not mean cholesterol isn’t a problem.

Bottom line:

This situation is:
Not rare.
Not a failure.
Often a sign that stronger, non-statin therapy is needed.
A lipid specialist or preventive cardiologist would likely:

Rule out secondary causes.
Confirm true statin intolerance.
Consider PCSK9 inhibitors or inclisiran.

Here are links to trustworthy sources that support the key points from the above explanation about Zetia (ezetimibe), Nexletol (bempedoic acid), statin intolerance, and other non-statin LDL-lowering therapies:

1. Non-statin therapies:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635697/ (PMC article on non-statin options and guidelines) �
PMC

2. Ezetimibe (Zetia) reduces LDL by about 15–25% non-statin option:
https://www.heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia/cholesterol-medications �
http://www.heart.org

3. Bempedoic acid (component of Nexletol / Nexlizet) statin-intolerant
https://consultqd.clevelandclinic.org/statin-intolerance-and-new-lipid-lowering-treatments �
Cleveland Clinic
NEXLIZET & NEXLETOL prescribing info page (with indication for statin-intolerant patients):
https://www.nexlizethcp.com/statin-intolerance-evidence/ (trial and safety details for bempedoic acid) �
ESPNEX

4. Study showing additive LDL lowering from ezetimibe + bempedoic acid:
https://www.tctmd.com/news/bempedoic-acidezetimibe-combo-lowers-ldl-cholesterol-high-risk-patients �
tctmd.com
Wikipedia summary of LDL reductions with the combination:
https://en.wikipedia.org/wiki/Bempedoic_acid/ezetimibe �
Wikipedia

5. PCSK9 inhibitors (e.g., evolocumab & alirocumab) statin-intolerant patients:
https://consultqd.clevelandclinic.org/statin-intolerance-and-new-lipid-lowering-treatments (ODYSSEY ALTERNATIVE trial results showing ~45% LDL reduction) �
Cleveland Clinic

6. Guidelines & consensus statements:
https://www.jacc.org/doi/10.1016/j.jacc.2022.07.006 �
JACC
NIH/NLM cholesterol management guideline overview including non-statin substitutions:
https://www.ncbi.nlm.nih.gov/books/NBK305897/ �