Empagliflozin

Detailed information

General information about assessment reports

Since 2006, an Environmental Risk Assessment (ERA) for the active pharmaceutical substance shall accompany an application for a marketing authorisation in EU for a medicinal product for human use. Parts of environmental data are available in the public assessment report (PAR/EPAR for centrally approved medicines). Environmental considerations are not included in the benefit-risk assessment for human medicines. If new data emerge after approval that necessitate an update of the environmental risk assessment, a variation application (“type IB C.I.z variation”) must be submitted to the regulatory authority.

The PEC (predicted environmental concentration) values used to calculate risk in the manufacturers' assessment reports are based on the estimated use of the medicinal product to which the assessment report relates, as well as possibly other products from the same company, not all medicinal products containing the same active substance.

Assessment report Glyxambi 2016

There are several assessment reports for Jardiance (empagliflozin), Glyxambi (empagliflozin, linagliptin) and Synjardy (empagliflozin, metformin) that include environmental data on empagliflozin. The company responsible for all three medicinal products is Boehringer Ingelheim. One of the earliest reports is presented here. This is followed by information from a 2024 Synjardy assessment report concerning the extended indication.

Assessment report for Glyxambi about empagliflozin, 15 September 2016, EMA/749639/2016. Empaglifozin forms a metabolite (M3).

Hazard

Persistence parent: DT₅₀, water = 2.3/2.1 d (r/p), DT₅₀, sediment = 4.9/3.6 d (r/p), DT₅₀, whole system = 2.5/2.5 d (r/p), r=river, p=pond, DT₅₀ values corrected to 12°C; Conclusion: not P
Persistence metabolite M3: DT₅₀, sediment = 169/125 (r/p), DT₅₀ values corrected to 12°C. Conclusion: P

Bioaccumulation: Log K_ow = 1.73, i.e. not B.

Chronic toxicity:There is NOEC for three trophic levels, lowest NOEC for fish 2400 microg/L.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:
PEC = 0.125 microg/L.
PNEC = Lowest NOEC, 2400 microg/L/10 (Assessment Factor (AF) for chronic studies with three species) = 240 microg/L.
PEC/PNEC = 0,00052 which gives the risk insignificant.

Assessment report Synjardy 2024

Assessment report for Synjardy about empagliflozin in relation to the extension of indication, EMA/464344/2024.

Hazard

Persistence: The parent compound empagliflozin shows short half‑lives in water (2.3–2.6 days) and sediment (4.1–5.5 days). However, some transformation products are highly persistent: TP M3 is very persistent in sediment, and TP M12 is very persistent in water. TP stands for Transformation Product. In OECD 308 water–sediment studies, the parent compound showed very short half‑lives: about 1.1–1.2 days in water and 1.9–2.6 days in sediment. The whole‑system DT₅₀ was around 1.3 days. A significant fraction (25–26%) shifted to the sediment. These results indicate rapid degradation with notable partitioning to sediment.

Bioaccumulation: Log K_ow = 1.73.

Toxicity: There are data for 3 trophic levels, most sensitive NOEC for fish 2400 microg/L.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

Refined PEC_{surface water} = 0.00034 microg/L.

PNEC = Lowest NOEC, 2400 microg/L/10 (Assessment Factor (AF) for chronic studies with three species) = 240 microg/L.

PEC/PNEC = 0.0000014 which gives the risk insignificant.

Fass environmental information

Fass environmental information for Glyxambi about empagliflozin from Boehringer Ingelheim (downloaded 2026-01-13).

Excretion (metabolism)

"After oral administration of Empagliflozin most of the radioactive dose was recovered in urine (54.4%) and feces (41.1%). Unchanged Empagliflozin was the most abundant component in urine and feces, representing 43.5% and 82.9% of radioactivity, respectively. The most abundant metabolites in urine were two glucuronide conjugates (7.8-13.2% of dose) and in feces a tetrahydrofuran ring-opened carboxylic acid metabolite (1.9% of dose). Thus, the environmental risk assessment should be performed on the data of the parent compound."

Hazard

Persistence: Empagliflozin was not readily biodegradable in an OECD 301B study (0 % degradation). However, in an OECD 308 simulation study it dissipated rapidly from the water phase, with short DT₅₀ values in water and sediment and formation of multiple transformation products. Less than 15 % of the parent compound remained after 120 days. Based on these combined data, empagliflozin is considered to be degraded in the environment.

Bioaccumulation: "The n-octanol/water partition coefficient was in an OECD Guideline 107 (GLP) study determined to 1.73 at pH 7.0."

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish (Danio rerio) NOEC 35d (length, wet weight, dry weight) = 2400 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2022. PEC/PNEC = 0.00030 which gives the risk insignificant.

Environmental assessment by Goodpoint 2026

Regardless of whether the risk assessment is based on the fish plasma model, on standardized ecotoxicological tests, or on more specific sublethal effects in fish, the environmental risk for all four investigated SGLT‑2 inhibitors (dapagliflozin, empagliflozin, ertugliflozin and canagliflozin) is assessed as very low from a Swedish perspective. Depending on how different effect measures and environmental properties are weighted, the risk could increase or decrease slightly if one substance were replaced by another, but in all cases the environmental risk would still be considered very low given the current state of knowledge. Therefore, no substitutions are recommended from an environmental risk perspective.