New Cholesterol Drugs and Updated Guidelines Expand Treatment Options for Millions

Two major developments are reshaping how doctors treat high cholesterol, and new guidelines may bring millions more Americans into treatment eligibility.

On July 16, the FDA approved Lipfendra, the generic name enlicitide, as the first oral PCSK9 inhibitor for adults with high LDL cholesterol. The once-daily pill can be used in addition to statins or as a replacement for them. In two clinical trials supporting the approval, Lipfendra lowered LDL cholesterol in patients who could not achieve their target levels on statins alone.

Separately, a systematic review and meta-analysis published in JACC: Advances on July 22 found that inclisiran, a twice-yearly injectable medication, led to a 49% greater reduction in LDL cholesterol compared with placebo. The analysis examined nine randomized controlled trials and found consistent results across patients receiving different background lipid-lowering therapies, according to a report by Healthline.

Inclisiran works by targeting the synthesis of certain proteins that can raise LDL levels. Because it is administered only twice a year, it may offer an option for people who struggle to take daily medications consistently.

Kevin Shah, MD, a board-certified cardiologist and Program Director of Heart Failure Outreach at MemorialCare Heart and Vascular Institute at Long Beach Medical Center in California, commented on the analysis. "The data is important because while there are mixed responses depending on which trial is considered, the overall trend is reassuring that the drug's impact on LDL concentrations is consistent," he said. Shah was not involved in the study.

He added a note of caution. "The cardiology community is excited about this therapeutic option, but we do continue to await outcomes trials, which would confirm that the degree of LDL lowering also lowers risk of heart attack and stroke," he said.

Statins remain the first-line treatment for high cholesterol. However, some patients do not reach guideline-recommended LDL levels because of statin intolerance, an inadequate response, or high residual cardiovascular risk. Both inclisiran and Lipfendra are positioned as options for those patients.

Earlier in 2026, the American Heart Association, the American College of Cardiology, and several other medical organizations released updated cholesterol screening and management guidelines. Those guidelines suggest that more than half of all U.S. adults may now be eligible for statin therapy, a significant expansion from previous recommendations.

The combination of new drug approvals, new data on inclisiran, and broader eligibility guidelines represents one of the larger shifts in cholesterol care in recent years. Outcomes trial results for inclisiran are still pending.