Can I Take Glycine With Jardiance (Empagliflozin)?

What Glycine and Empagliflozin Each Do

Glycine is a conditionally essential amino acid involved in collagen synthesis, glutathione production, neurotransmission, and bile acid conjugation. Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that blocks renal glucose reabsorption at the proximal tubule, forcing roughly 40 to 80 g of glucose per day into the urine [1].

Glycine's Metabolic Role

Glycine acts as an inhibitory neurotransmitter in the brainstem and spinal cord, which is one reason it appears in sleep-support supplements. It also serves as a precursor to glutathione (the body's primary intracellular antioxidant) and to creatine. A 2004 study in 12 healthy volunteers found that 75 mg/kg of oral glycine (~5 g for a 70-kg adult) reduced the glycemic response to a glucose load by stimulating glucagon-like peptide 1 (GLP-1) secretion [2]. Plasma glycine concentrations are consistently lower in people with type 2 diabetes and metabolic syndrome compared to normoglycemic controls, according to a 2019 meta-analysis of 28 metabolomics studies (pooled N = 19,183) published in Diabetes Care [3].

Empagliflozin's Mechanism

Empagliflozin selectively inhibits SGLT2, which handles approximately 90% of renal glucose reabsorption. The EMPA-REG OUTCOME trial (N = 7,020) demonstrated a 38% relative risk reduction in cardiovascular death among type 2 diabetes patients with established cardiovascular disease receiving empagliflozin 10 mg or 25 mg versus placebo over a median 3.1 years [4]. The drug does not depend on insulin secretion, so its glucose-lowering effect is independent of beta-cell function.

Is There a Drug-Supplement Interaction?

The short answer: no pharmacokinetic interaction has been documented. Empagliflozin is metabolized primarily by UGT1A3, UGT1A8, UGT1A9, and UGT2B7 glucuronidation pathways, with minor CYP involvement [5]. Glycine does not inhibit or induce any of these UGT isoforms. It is not a substrate for CYP450 enzymes. The two compounds are cleared through entirely separate routes.

Pharmacokinetic Assessment

Empagliflozin reaches peak plasma concentration (Tmax) at approximately 1.5 hours after oral dosing, with a terminal half-life of 12.4 hours [5]. Glycine, taken orally, is absorbed in the jejunum via amino acid transporters (primarily PAT1/SLC36A1) and reaches peak plasma levels within 30 to 60 minutes. Because their absorption windows differ and neither compound competes for the same transporters or metabolic enzymes, co-administration does not alter the bioavailability of either substance.

Pharmacodynamic Overlap

The interaction that matters here is pharmacodynamic, not pharmacokinetic. Both glycine and empagliflozin can lower blood glucose through different mechanisms. Empagliflozin increases urinary glucose excretion. Glycine may modestly improve insulin sensitivity and stimulate GLP-1 release [2]. A 2018 randomized controlled trial in 74 patients with metabolic syndrome found that 15 g/day of glycine for three months reduced HbA1c by 0.5% compared to placebo (P = 0.03) [6]. That effect size is smaller than empagliflozin's typical HbA1c reduction of 0.7% to 0.8% [4], but the two effects could be additive.

This additive glucose-lowering potential becomes clinically relevant if a patient is also taking insulin, a sulfonylurea, or another secretagogue. The risk of hypoglycemia from empagliflozin alone is low (0.5% to 1% in monotherapy trials), but stacking glycine on top of a multi-drug regimen that already includes insulin could push fasting glucose below target.

Dose-Separation Guidelines

No formal dose-separation window is required based on available evidence. Neither compound interferes with the other's absorption.

Practical Timing Recommendations

A reasonable approach is to take empagliflozin in the morning with breakfast (its labeled dosing) and glycine in the evening. Many people use glycine at bedtime for sleep support, which naturally creates a 10- to 14-hour separation. A 2015 study in the journal Neuropsychopharmacology confirmed that 3 g of glycine taken before bed improved subjective sleep quality and next-day cognitive performance without causing morning sedation (N = 11, crossover design) [7].

When Separation Might Matter

If a patient takes glycine at high doses (10 g or above) specifically for metabolic purposes, taking it at a different time from empagliflozin allows easier attribution if gastrointestinal side effects (nausea, bloating) occur. Both glycine at high doses and empagliflozin can cause mild GI discomfort, so staggering them simplifies troubleshooting.

Monitoring Recommendations

Patients taking both glycine and empagliflozin should follow the same monitoring schedule as standard SGLT2 inhibitor therapy, with a few additions.

Blood Glucose and HbA1c

Check fasting glucose at baseline, then at 4 weeks after adding glycine. If stable, revert to the standard every-three-month HbA1c schedule. The American Diabetes Association (ADA) 2024 Standards of Care recommend HbA1c testing at least twice yearly in patients meeting treatment goals and quarterly in patients whose therapy has changed [8].

Renal Function

Empagliflozin carries a labeled recommendation for eGFR monitoring. The 2024 KDIGO guidelines recommend checking eGFR and urine albumin-to-creatinine ratio (UACR) at least annually, and more frequently if eGFR is <60 mL/min/1.73 m² [9]. Glycine does not alter renal function in published human studies at doses up to 15 g/day [6], but because it is renally cleared, patients with significantly reduced kidney function should discuss high-dose glycine with their prescriber.

Ketone Awareness

SGLT2 inhibitors carry an FDA boxed warning for diabetic ketoacidosis (DKA), including euglycemic DKA where blood glucose may be normal or only mildly elevated [10]. Glycine does not increase ketone production. Patients should still know the symptoms of DKA (nausea, vomiting, abdominal pain, fatigue, difficulty breathing) and check urine or blood ketones if these appear.

Glycine's Evidence in Diabetes and Cardiometabolic Health

The rationale for combining glycine with an SGLT2 inhibitor extends beyond sleep support. Several lines of evidence suggest glycine has independent cardiometabolic benefits.

Insulin Sensitivity

A 2023 randomized trial published in Cell Reports Medicine studied GlyNAC (glycine 1.33 mmol/kg/day plus N-acetylcysteine 0.81 mmol/kg/day) in 24 older adults for 16 weeks. Participants receiving GlyNAC showed improved insulin resistance (HOMA-IR decreased by 26.2% vs. Placebo, P = 0.002) and reduced oxidative stress biomarkers [11]. The glycine component is thought to restore intracellular glutathione, which in turn improves mitochondrial fatty acid oxidation. Whether glycine alone (without N-acetylcysteine) produces the same magnitude of effect remains unconfirmed in a large trial.

Endothelial Function

"Glycine has vasoprotective properties independent of its role in glutathione synthesis," wrote Dr. Rajagopal Sekhar of Baylor College of Medicine in a 2022 commentary in The Journal of Clinical Investigation [12]. Glycine activates glycine-gated chloride channels on endothelial cells and macrophages, which may reduce vascular inflammation. This is potentially complementary to empagliflozin's own cardiovascular benefits demonstrated in EMPA-REG OUTCOME and EMPEROR-Preserved [4][13].

Collagen and Musculoskeletal Health

Patients on SGLT2 inhibitors sometimes report increased urinary frequency and mild volume depletion. Glycine, as a major component of collagen (roughly one-third of collagen's amino acid residues), supports connective tissue integrity. A 2019 study in the American Journal of Clinical Nutrition found that 15 g of gelatin (rich in glycine) taken with vitamin C before exercise increased collagen synthesis rate by roughly twofold compared to placebo (N = 8, crossover) [14]. This is relevant for patients concerned about joint or tendon health while managing diabetes.

What If You're Already Taking Both?

If you have been taking glycine alongside Jardiance without issues, the available evidence suggests you can continue. There is no signal in pharmacovigilance databases (FDA Adverse Event Reporting System, or FAERS) associating the combination with unexpected adverse events.

Steps to Confirm Safety

Check your most recent fasting glucose and HbA1c. If HbA1c is within your target range (typically <7.0% for most adults with type 2 diabetes, per ADA guidelines [8]) and you have not experienced unexplained hypoglycemia episodes, the combination is working as expected. Inform your prescriber that you are taking glycine so it appears in your medication reconciliation.

Red Flags to Watch

Seek medical attention if you notice symptoms of hypoglycemia (shakiness, sweating, confusion, heart pounding) that you did not experience before adding glycine. Also watch for signs of euglycemic DKA if you are on empagliflozin: persistent nausea, rapid breathing, or fruity-smelling breath even with normal blood sugar readings [10].

Special Populations

Heart Failure Patients

Empagliflozin holds an FDA indication for heart failure with reduced or preserved ejection fraction, based on EMPEROR-Reduced (N = 3,730) and EMPEROR-Preserved (N = 5,988) [13]. Glycine's mild hypotensive effect has not been studied in heart failure populations specifically. These patients should add glycine only under clinician supervision, as even small shifts in volume status or blood pressure can be clinically meaningful.

Chronic Kidney Disease

Empagliflozin is approved for CKD risk reduction (EMPA-KIDNEY, N = 6,609) [15]. Glycine clearance depends partly on renal function. While no dose adjustment for glycine exists in published literature, patients with eGFR <30 mL/min/1.73 m² should limit glycine to 3 g/day or less and monitor serum amino acid levels if available.

Patients on Insulin or Sulfonylureas

The additive glucose-lowering risk is highest in this group. If adding glycine at doses above 5 g/day, increase self-monitoring of blood glucose to twice daily for the first two weeks and discuss potential sulfonylurea dose reduction with your prescriber.

Glycine Dosing for Different Goals

The right glycine dose depends on why you are taking it. For sleep support, 3 g before bed is the most studied dose [7]. For metabolic or antioxidant purposes, studies have used 5 to 15 g per day, often divided into two or three doses [6][11]. For collagen synthesis support, 5 to 15 g of glycine-rich collagen peptides or gelatin, taken with 50 mg of vitamin C, is the protocol tested in exercise physiology research [14].

Start at 3 g per day for the first week, then increase gradually. GI side effects (mild nausea, soft stools) are uncommon but tend to appear at doses above 9 g per day.

Bottom Line

Glycine and empagliflozin do not share metabolic pathways, transporters, or enzyme systems. Their interaction risk is pharmacodynamic (additive glucose lowering), not pharmacokinetic. Monitor fasting glucose for the first month after adding glycine, maintain your standard HbA1c and renal panel schedule, and inform your prescriber. Patients on multi-drug diabetes regimens that include insulin or sulfonylureas should increase glucose monitoring frequency when starting glycine above 5 g per day.