Anatomical cross-section of a human artery showing cholesterol plaque buildup and restricted blood flow. 3d illustration
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If your cholesterol has remained persistently elevated despite taking a statin, you may have heard your health care provider mention drugs like Repatha or Praluent — injections that block a protein called PCSK9 and help your liver pull more “bad” LDL cholesterol out of your blood.
On July 16, 2026, the FDA approved the first pill version of this same idea: Lipfendra (enlicitide), a once-daily tablet for adults with high cholesterol (LDL-C), including an inherited form called familial hypercholesterolemia.
“This is an incredible breakthrough in heart disease prevention and care. This revolutionary new oral medication allows us to get LDL cholesterol levels (so called ”bad cholesterol”) to levels we have never seen before with oral medications.” said Dr. Mohammed Alo, Assistant Clinical Professor of Medicine at Midwestern University Downers Grove, Illinois, Assistant Clinical Professor of Medicine at Ohio University Athens, Ohio. Dr. Alo is known for providing concise and clear public messaging managing lipid disorders and other complex cardiac conditions.
How Well Does iIt Work?
In two large studies, Lipfendra lowered LDL cholesterol (LDL-C) by more than half compared with a placebo — a 56% reduction in one trial of adults with heart disease or high risk for it, and a 59% reduction in a second trial of people with the inherited form of high cholesterol. It also improved other cholesterol-related markers health care providers monitor, including ApoB and non-HDL cholesterol. Those numbers are in the same range as what the injectable drugs achieve, which is notable for a pill.
Dr. Abeer Berry, Director of Noninvasive Cardiology, DMC Huron Valley Sinai Hospital strongly agreed. “We are one step closer to eradicating heart disease. As of July 16, the first oral PCSK9 inhibitor has been approved for consumer use. This once daily oral tablet is capable of lowering your LDL cholesterol, also known as your ‘bad cholesterol,’ by nearly 60%.”
What About Lp(a)?
Lp(a), short for lipoprotein(a), is a lesser-known, highly atherogenic and inherited cholesterol-like particle that raises the risk of coronary artery disease (CAD), heart attacks, strokes along with risk for aortic valve abnormalities–but isn’t affected by diet, exercise, or statins. The good news: Lipfendra lowered Lp(a) too, by roughly a quarter in the main trials. The important caveat is that this isn’t unique to Lipfendra — the injectable PCSK9 drugs (Repatha, Praluent) and a couple of other newer agents all lower Lp(a) by a similar amount, around 25%. So if a very high Lp(a) is your main concern, Lipfendra doesn’t outperform what’s already available; it simply offers the same modest benefit in pill form. Medicines designed specifically to target Lp(a) are still being tested and aren’t approved yet.
Cholesterol formation, fat, artery, vein, heart. Red blood cells, blood flow. Narrowing of a vein for fat formation. Surgery operation, 3d render
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Lipfendra Vs. Repatha: What’s The Real Difference?
No study has pitted Lipfendra directly against Repatha (evolocumab) head-to-head, so comparisons are indirect. What we can say is this: the amount of LDL lowering looks similar between the two medications. The biggest practical difference is the form — a daily pill instead of an injection every two to four weeks — which may appeal to people who have fear of needles or find injection schedules challenging to keep up with.
“The effectiveness [of Lipfendra] is similar to an injectable PCSK9 inhibitor, which is most commonly administered every two weeks.”added Berry.
The biggest scientific difference, though, is track record. Repatha has been shown in a large, multi-year study to actually reduce heart attacks and strokes– not just lower cholesterol numbers on a lab report. Lipfendra hasn’t been tested long enough yet to know whether it does the same — that answer is expected from a large ongoing trial with over 14,500 participants. Until those results are in, Lipfendra is approved only for lowering cholesterol–not (yet) for proven heart-attack or stroke prevention, even though experts expect it likely will show similar benefit given how closely it mirrors the injectable drugs.
Is It Safe?
In the larger trial, side effects with Lipfendra were similar to placebo. In the familial hypercholesterolemia trial, diarrhea (7% vs. 2% with placebo) and dizziness (9% vs. 4%) were somewhat more common, though similar numbers of people in each group stopped treatment because of side effects.
“In contrast to the injectable version, one can avoid possible injection site reactions and flu like symptoms but may expect possible diarrhea or dizziness.” explained Berry.
The Bottom Line
Lipfendra is a genuine advance for people who need more LDL lowering than a statin alone provides and who would prefer a pill to an injection. It works about as well as the existing injectable options, including for Lp(a), but doesn’t yet have the long-term proof of preventing heart attacks that Repatha has. If your cholesterol remains high despite treatment, this is a good conversation to have with your doctor — including whether a pill-based option now makes sense for you.
“With this option of lipid lowering therapy, we are hopeful to continue to reduce the prevalence of cardiovascular disease – the number one cause of death in the United States,” Berry emphasized.