Ertugliflozin

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

There are assessment reports for Segluromet (ertugliflozin, metformin), Steglatro (ertugliflozin) and Steglujan (ertugliflozin, sitagliptin). The company responsible for all three medicinal products is Merck Sharp & Dohme. This document presents the assessment report for Steglatro, dated 25 January 2018, EMA/86938/2018.

Hazard

Persistence: OECD 314B indicates that ertugliflozin shows high primary degradation in sludge. It is also degraded in surface water to several transformation products, with a DT₅₀ of 0.55 days. OECD 308 studies report DT₅₀ values of 45.3–56.8 days (12 °C) in water‑sediment systems, with both water‑ and sediment‑specific values below the persistence criteria (DT_50,water < 40d, DT_50,sediment, < 120d). Overall, the data indicate that ertugliflozin is not persistent in water‑sediment systems. The substance shows some sediment accumulation (21.6–35.5 % AR) and has relatively low adsorption coefficients (Kdoc 198–967 L/kg).

Bioaccumulation: Log K_ow = 2.47 (pH 7).

Toxicity: There are data for 3 trophic levels, most sensitive fish NOEC 1000 microg/L.

Risk

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

PEC_{surface water} = 0.62 microg/L.

PNEC = Lowest NOEC, 1000 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 100 microg/L

PEC/PNEC = 0.0062 which gives the risk insignificant.

Fass environmental information

Fass environmental information for Steglatro from Merck Sharp & Dohme (retrieved on 2026-01-13). The same environmental information for ertugliflozin applies to both Segluromet and Steglujan.

Hazard

Persistence: OECD 314B, 309 and 308 studies show rapid degradation of ertugliflozin in sludge, surface water and water‑sediment systems. The total system DT₅₀ was 21–27 days, below the 32‑day threshold. Therefore, ertugliflozin is considered degraded in the environment.

Ertugliflozin degrades into several transformation products, including TP2, TP4 and especially TP5, the dominant product in water–sediment systems. TP5 appears at high initial levels and further degrades in the total water–sediment systems with calculated DT₅₀ values of 24.8 and 3.5 days in the two test systems.

Bioaccumulation: Log D = 2.47 at pH 7.

Toxicity: There are data for 3 trophic levels, most sensitive fish NOEC 1000 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2022.

PEC = 0.00013 microg/L.

PNEC = Lowest NOEC, 1000 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 100 microg/L.

PEC/PNEC = 0.0000013 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.