Can I Take Glycine with Leqvio (Inclisiran)?

What Is Leqvio (Inclisiran) and How Does It Work?

Leqvio is a small interfering RNA (siRNA) therapy that silences the gene encoding PCSK9 in the liver. By blocking PCSK9 production, it prevents the degradation of LDL receptors on hepatocyte surfaces, allowing those receptors to pull more LDL-C out of circulation. A single 284 mg subcutaneous injection is given on Day 1, repeated at Month 3, and then every 6 months thereafter.

Mechanism of Action

Inclisiran is taken up by hepatocytes via the asialoglycoprotein receptor (ASGR1) through a GalNAc conjugate on the siRNA molecule. Once inside the cell, it enters the RNA-induced silencing complex (RISC) and catalytically degrades PCSK9 messenger RNA. Because the drug acts entirely inside the hepatocyte and does not circulate at meaningful plasma concentrations after the first 48 hours, it has essentially no systemic pharmacokinetic interactions with dietary supplements or other drugs. The FDA prescribing information for inclisiran confirms it is not a substrate, inhibitor, or inducer of CYP450 enzymes, P-glycoprotein, or OATP transporters. [1]

Established Efficacy Data

The ORION-11 trial (N=1,617 patients with ASCVD or ASCVD risk equivalents plus elevated LDL-C) showed inclisiran 284 mg produced a 49.9% placebo-corrected reduction in LDL-C at Day 510, with 80% of participants also on maximally tolerated statin therapy. [2] A companion trial, ORION-9 (N=482 patients with heterozygous familial hypercholesterolemia), found a 39.7% placebo-corrected LDL-C reduction with a similar every-6-months regimen. [3]

These reductions position inclisiran alongside injectable PCSK9 monoclonal antibodies such as evolocumab (Repatha) and alirocumab (Praluent), but with a twice-yearly dosing advantage that improves adherence.

What Is Glycine and Why Do People Take It?

Glycine is the simplest amino acid and is conditionally essential during periods of physiological stress, rapid growth, or illness. Endogenously, the liver produces roughly 3 g per day, but dietary intake from collagen-rich foods adds another 2 to 4 g in most Western diets. Supplemental doses range from 2 g at bedtime for sleep support up to 15 g per day for collagen synthesis, metabolic health, or renal protection in chronic kidney disease.

Common Supplement Uses

• Sleep quality. A 3 g oral dose of glycine taken 30 to 60 minutes before bedtime reduced self-reported fatigue and improved PSG-measured sleep efficiency in a randomized crossover study of 11 volunteers. [4]
• Glycemic and metabolic health. Glycine acts as a co-agonist at NMDA receptors and modulates glucagon secretion. Observational data from the EPIC-Norfolk cohort linked higher plasma glycine to lower type 2 diabetes incidence (HR 0.71 per 1-SD increase, P<0.001). [5]
• Collagen synthesis. Hydroxyproline, the backbone of collagen triple helix, requires glycine at every third residue. Athletes and individuals with osteoarthritis sometimes supplement 5 to 10 g per day alongside vitamin C to support joint tissue repair.
• Chronic kidney disease. Some nephrology protocols include glycine as part of antioxidant cocktails because glycine attenuates renal tubular oxidative stress in rodent ischemia-reperfusion models, though human RCT data remain limited.

Safety Profile

The tolerable upper intake for glycine has not been formally set by the Institute of Medicine, but clinical trials and case series report no serious adverse events at doses up to 60 g per day in short-term use. At 90 g per day in schizophrenia trials, mild nausea and loose stools were the predominant complaints. [6] For the 2 to 15 g per day range relevant to most supplement users, glycine is considered safe in otherwise healthy adults.

Does Glycine Interact with Inclisiran Pharmacokinetically?

No pharmacokinetic interaction has been identified, and the mechanistic basis for one is essentially absent.

Why Inclisiran Is Unlikely to Be Affected

Inclisiran's plasma half-life is approximately 9 hours. Within 48 hours of injection, plasma concentrations fall below the limit of quantification, while the pharmacodynamic effect persists for 6 months because the siRNA remains active inside RISC inside hepatocytes. [1] Glycine is absorbed in the small intestine via the sodium-dependent neutral amino acid transporter (SLC6A19) and is then metabolized in multiple tissues through the glycine cleavage system (GCS). Neither pathway intersects with the asialoglycoprotein receptor uptake mechanism that inclisiran depends on.

Glycine does not inhibit or induce any of the enzymes or transporters listed in the inclisiran prescribing information, which identifies no significant clinical drug-drug interactions at all. [1]

What the Databases Say

The Natural Medicines database (Therapeutic Research Center) assigns glycine a "no known interaction" rating with inclisiran as of the most recent update. The FDA's drug interaction labeling for Leqvio lists no supplement interactions whatsoever, consistent with the mechanistic analysis above. [1]

Are There Pharmacodynamic Reasons to Be Careful?

Pharmacodynamic interactions occur when two agents act on the same physiological pathway, even if they never encounter each other chemically. For most Leqvio patients, none exists with glycine. Two subgroups deserve closer attention.

Patients with Type 2 Diabetes or Pre-Diabetes

Inclisiran does not affect glucose metabolism directly. Glycine, on the other hand, may improve insulin sensitivity. A 12-week RCT of glycine supplementation (5 g three times daily, total 15 g/day) in 60 patients with metabolic syndrome showed a significant reduction in fasting insulin (P<0.05) and a trend toward lower fasting glucose compared with placebo. [7]

If a patient with type 2 diabetes is already on sulfonylureas, insulin, or GLP-1 receptor agonists, adding high-dose glycine could modestly increase the risk of hypoglycemia. The absolute risk is low, but patients should monitor fasting glucose more frequently during the first 4 to 6 weeks of glycine supplementation and discuss any dose adjustments with their prescriber.

Patients with Chronic Kidney Disease (CKD)

Inclisiran is approved for use in patients with CKD, and no dose adjustment is required even with severe renal impairment (eGFR <30 mL/min/1.73 m²). [1] Glycine itself is renally cleared, and while short-term high-dose glycine is generally well tolerated in CKD, patients on protein-restricted diets should account for the additional amino acid load. A 15 g/day glycine supplement adds approximately 15 g of dietary protein equivalent, which could be material for a patient capped at 40 to 50 g total protein per day.

Patients with CKD Stage 4 or 5 taking both inclisiran and glycine should discuss the added amino acid load with their nephrologist or dietitian.

Glycine and Cardiovascular Risk: Is There a Synergistic Benefit?

This question does not have a definitive answer, but the signal is worth knowing.

Observational and Mechanistic Data

Plasma glycine has been inversely associated with risk of myocardial infarction in two separate Mendelian randomization analyses. The EPIC-Norfolk cohort data cited above found that individuals in the highest glycine tertile had a 27% lower risk of incident type 2 diabetes after adjustment for confounders. [5] A separate metabolomics sub-study of the PREDIMED trial found that higher baseline plasma glycine predicted less cardiovascular event risk over 5 years of follow-up, though that analysis was hypothesis-generating. [8]

Because inclisiran's job is reducing LDL-C-driven ASCVD risk, and glycine may independently reduce metabolic cardiovascular risk through separate pathways (glucagon suppression, glycemic improvement, anti-inflammatory effects via glycine-gated chloride channels), the two interventions are theoretically complementary rather than opposing. No clinical trial has prospectively studied this combination.

The HealthRX Co-Administration Decision Framework for Inclisiran Patients

Use this framework before starting any supplement alongside Leqvio.

| Step | Question | Action if "Yes" | |------|----------|-----------------| | 1 | Does the supplement use CYP3A4, CYP2C9, P-gp, or OATP1B1/1B3? | Flag to prescriber. Inclisiran does not use these, but other concurrent drugs might | | 2 | Does the supplement affect LDL-C or lipid absorption? | Monitor lipid panel at next scheduled visit | | 3 | Does the supplement affect glucose or insulin sensitivity? | Add fasting glucose or HbA1c to monitoring plan if patient has diabetes or pre-diabetes | | 4 | Does the supplement add significant protein load (>10 g/day amino acids)? | Discuss with nephrologist or dietitian if eGFR <45 | | 5 | Is the supplement taken by injection? | Separate injection site by at least 2 inches and rotate sites per standard practice |

Glycine scores "No" on Steps 1 and 2, "Possibly" on Step 3 in at-risk patients, "Yes" on Step 4 at doses above 10 g/day, and "No" on Step 5. The net assessment is low risk with targeted monitoring in diabetic and CKD subgroups.

Practical Guidance: Timing, Dose, and Monitoring

Does Timing of Glycine Relative to Inclisiran Injection Matter?

No. Because inclisiran leaves plasma within 48 hours and glycine acts via entirely different mechanisms, there is no clinically meaningful window to separate them. Patients do not need to stop glycine before or after their Leqvio injection.

Recommended Glycine Doses for Common Goals

| Goal | Typical Dose | Evidence Base | |------|-------------|---------------| | Sleep quality | 3 g, 30 to 60 min before bedtime | Randomized crossover trial, N=11 [4] | | Metabolic health | 5 g three times daily (15 g/day) | 12-week RCT in metabolic syndrome [7] | | Collagen / joint support | 5 to 10 g/day with vitamin C | Mechanistic + small RCT data | | CKD antioxidant protocols | 2 to 5 g/day | Case series; discuss with nephrologist |

For most Leqvio patients, 3 g at bedtime for sleep carries essentially no interaction concern. Doses above 10 g/day warrant a brief conversation with the prescriber, particularly in patients with diabetes.

Monitoring Checklist

1. Lipid panel. Inclisiran patients should already have fasting lipids drawn before each injection (Day 1, Month 3, then every 6 months). No extra lipid monitoring is needed for glycine co-administration.
2. Fasting glucose or HbA1c. Add this at the 3-month follow-up visit if the patient has type 2 diabetes, pre-diabetes, or metabolic syndrome and is taking glycine above 5 g/day.
3. Injection-site records. Inclisiran is injected subcutaneously in the abdomen, upper arm, or thigh. Glycine is oral, so there is no site interaction.
4. Renal function (eGFR, BUN, creatinine). No additional testing beyond standard CKD monitoring is required unless daily glycine dose exceeds 10 g in a patient with eGFR <45.

What Do Guidelines Say About Supplements and PCSK9-Targeting Therapy?

The 2022 ACC/AHA Guideline on the Management of Blood Cholesterol does not specifically address dietary supplements in the context of PCSK9 inhibitor or siRNA therapy. [9] The guideline notes that clinicians should "assess adherence and response to lipid-lowering therapy" at each visit, which implicitly includes a medication and supplement reconciliation.

The European Society of Cardiology 2021 Dyslipidaemia Guidelines similarly do not list specific supplement contraindications for inclisiran but recommend that prescribers document all concurrent supplements at the time of initiating any LDL-lowering therapy. [10]

The absence of guideline-level warnings about glycine with inclisiran is consistent with the mechanistic safety analysis: no interaction pathway exists to require a warning.

What Clinicians at HealthRX Tell Patients

The HealthRX medical team follows a standard supplement-reconciliation protocol for all patients initiating Leqvio. Patients are asked to list every supplement, dose, and frequency at the time of prescribing and at each 6-month follow-up visit.

For glycine specifically, the clinical guidance is straightforward. Patients without diabetes taking 3 to 5 g per day can continue without modification. Patients with type 2 diabetes or metabolic syndrome taking glycine above 5 g per day should have their fasting glucose or HbA1c checked at the 3-month visit. Patients with CKD Stage 4 or 5 should discuss the total daily amino acid load with their nephrologist before starting any dose above 5 g per day.

No patient taking Leqvio needs to stop glycine based on current evidence.

When to Contact Your Prescriber

Contact your prescriber promptly if you experience any of the following after starting or increasing glycine alongside Leqvio:

• Symptoms of hypoglycemia (shakiness, sweating, confusion) if you take insulin or a sulfonylurea
• Nausea or gastrointestinal discomfort that begins within 1 to 2 weeks of starting glycine above 10 g/day
• New swelling, rash, or tenderness at prior inclisiran injection sites (this is more likely related to the injection itself than to glycine, but should be reported)
• Any unexpected change in blood pressure, though no mechanism links glycine to blood pressure changes in normotensive adults