Inclisiran (Leqvio) and Diabetes Risk
Inclisiran (Leqvio) does not increase the risk of diabetes, unlike statins, and may actually be a preferred option for patients with metabolic disturbances or prediabetes who require LDL-C lowering.
Evidence on Inclisiran and Diabetes Risk
Recent evidence strongly supports that inclisiran does not increase the risk of new-onset diabetes:
The 2024 International Lipid Expert Panel (ILEP) position paper specifically highlights that unlike statins, which dose-dependently increase the number of new-onset diabetes (NOD) cases, inclisiran has not been associated with increased risk of developing diabetes 1.
A 2025 systematic evaluation comparing inclisiran with evolocumab and atorvastatin found that inclisiran had a significantly lower risk of new-onset diabetes than atorvastatin. The reporting odds ratio (ROR) for type 2 diabetes was 195.03 for atorvastatin compared to only 0.95 for inclisiran 2.
A 2018 review of newer lipid-lowering therapies specifically noted that inclisiran and PCSK9 inhibitors have shown favorable results "without an increased risk of developing new-onset diabetes" 3.
Mechanism of Action and Safety Profile
Inclisiran works differently from statins:
Inclisiran is a small interfering RNA (siRNA) that prevents hepatic synthesis of PCSK9 by interfering with the translation of PCSK9 mRNA 4.
Unlike statins, which can affect glucose metabolism, inclisiran's targeted mechanism appears to avoid this metabolic effect.
The safety profile of inclisiran has been well-documented across multiple studies, with the main adverse effect being mild to moderate injection-site reactions 4.
Clinical Implications for Patient Management
For patients concerned about diabetes risk:
For patients with metabolic syndrome or prediabetes: Inclisiran may be preferred over statins due to its neutral effect on glucose metabolism 1.
For patients with established diabetes: Inclisiran can be used safely without concern for worsening glycemic control 5.
For statin-intolerant patients: Inclisiran represents a valuable alternative that doesn't carry the diabetes risk associated with statins 6.
Dosing and Administration
Inclisiran is administered as a subcutaneous injection initially, again at 3 months, and then every 6 months thereafter 1.
This twice-yearly administration schedule after the initial doses may improve adherence compared to daily oral medications or more frequent injections 4.
Cardiovascular Outcomes
While inclisiran effectively lowers LDL-C by approximately 50%, its effect on cardiovascular outcomes is still being evaluated:
Two large cardiovascular outcomes trials (ORION-4 and VICTORION-2P) are currently ongoing to determine the effect of inclisiran on cardiovascular morbidity and mortality 1.
In the ORION trials, inclisiran reduced LDL-C by 49-54% compared to placebo 1.
Conclusion
For patients requiring LDL-C lowering who are concerned about diabetes risk, inclisiran represents an excellent option that effectively reduces LDL-C without increasing the risk of developing diabetes. This makes it particularly valuable for patients with metabolic syndrome, prediabetes, or those who have experienced or are concerned about the diabetogenic effects of statins.