SGLT2 / SGLT1-2 inhibitors (dapagliflozin, sotagliflozin)
AstraZeneca (dapagliflozin); Lexicon Pharmaceuticals (sotagliflozin)
Modest adjunct benefits with a clinically important ketoacidosis risk.
What it is
SGLT2/SGLT1-2 inhibitors can modestly improve glucose outcomes, weight and insulin requirements alongside insulin in T1D, but increase diabetic ketoacidosis risk, sometimes without marked hyperglycemia. Dapagliflozin has a Japanese T1D indication; European T1D indications were withdrawn and US T1D approval remains absent.
Editorial review: .
Most recent recorded citation date: 2026-08-06. Only explicit date metadata is included; an undated citation may be newer. This does not mean every claim was reviewed on that date.
Trial status, labels and access can change between reviews. How we review the evidence · How to read the evidence
Evidence behind this assessment
Key evidence notes. Study results, product eligibility and access answer different questions.
- Who was studied?
- Study populations and analysis groups vary. Product age limits alone do not describe who was studied.See the linked studies and their populations →
- Benefit or performance
- Glycemic benefit: The efficacy was never the disputed part. The EMA authorised sotagliflozin in 2019 as an add-on to insulin in type 1 diabetes on the strength of its trial programme, and dapagliflozin was licensed for the same use in Europe and Japan — regulators do not grant a type 1 indication without a demonstrated glucose benefit. The effect is described as modest — reported as a fraction of a percentage point off HbA1c, plus added time in range — on top of insulin you keep taking.[2]
- Important harms and treatment burden
- Safety: Dapagliflozin T1D studies identify DKA as a common adverse reaction; it can occur without marked hyperglycemia. This is an increased risk in T1D, not a risk exclusive to T1D.[1]
- Approval and country access
- Not licensed for type 1 diabetes in the EU, the UK or the US. Licensed for type 1 in Japan. Off-label prescribing for type 1 elsewhere, using the type 2 product, varies by country and was not surveyed in the sources reviewed here.Approval, trial recruitment, local supply and funding are separate. Check the cited label or access source.
- Follow-up and remaining uncertainty
- Read the full discussion and original sources for follow-up duration and study limitations.
This record cites company or conference reports. Those sources may describe interim findings; their source type is shown in the source list.
Editorial score: calculation and evidence
A weighted editorial judgment on a 0–100 scale, not a probability of success or a measured treatment effect. Higher criterion scores mean more favorable assessments.
Default calculation: 65 × 25 + 20 × 25 + 65 × 15 + 60 × 20 + 25 × 15 = 4675; divide by total weight 100. Unrounded weighted result: 46.75.
The efficacy was never the disputed part. The EMA authorised sotagliflozin in 2019 as an add-on to insulin in type 1 diabetes on the strength of its trial programme, and dapagliflozin was licensed for the same use in Europe and Japan — regulators do not grant a type 1 indication without a demonstrated glucose benefit. The effect is described as modest — reported as a fraction of a percentage point off HbA1c, plus added time in range — on top of insulin you keep taking.[2]
Dapagliflozin T1D studies identify DKA as a common adverse reaction; it can occur without marked hyperglycemia. This is an increased risk in T1D, not a risk exclusive to T1D.[1]
Genuinely more than a glucose drug. In type 1 diabetes they are described as reducing total daily insulin dose and body weight, which is why sotagliflozin's European licence was written for people with a BMI of 27 or above. The cardiovascular and kidney protection this class is famous for is described as demonstrated in type 2 diabetes and chronic kidney disease, not in type 1 in the sources reviewed here, so we do not score it here.[2]
Dedicated phase 3 T1D programs establish modest glycemic efficacy, but EU T1D indications were withdrawn and US T1D approval remains absent. Resubmission requires further exposure/safety evidence.[2]
Dapagliflozin is approved for T1D in Japan. No US or EU T1D indication; UAE/Bahrain sotagliflozin approvals are for heart failure. US T1D resubmission targeted Q4 2026, subject to STENO1 data.[6]
These ratings concern add-on treatment alongside insulin in T1D. Maturity reflects the T1D evidence, and safety receives substantial editorial weight because risks differ by drug and population. For example, SGLT2 inhibitors can cause ketoacidosis even without markedly high glucose; this is not exclusive to T1D. Access reflects the stated indication and region, including whether a separate obesity indication applies.
Editor’s take
Ketone monitoring can reveal a risk that a glucose-only CGM misses, but monitoring alone does not remove the drug-associated DKA risk or validate routine T1D use. Continuous ketone sensing needs prospective outcome evidence before it can be treated as an effective prevention strategy.
The full picture
SGLT2 inhibitors reduce renal glucose reabsorption. Sotagliflozin also inhibits intestinal SGLT1. In T1D these are adjuncts to insulin, with modest glucose, weight and insulin-dose benefits; they do not replace insulin.
The defining risk
Diabetic ketoacidosis can develop without markedly high glucose. The European dapagliflozin safety communication calls DKA a common adverse reaction in its T1D studies. Normal-looking CGM readings therefore cannot exclude it.1
Ketone testing, insulin continuity and a clinician-agreed sick-day plan matter. Continuous ketone sensors may help detection, but detecting ketones does not itself prevent or treat DKA, and this review has not established that such sensors make SGLT2 treatment safe in routine T1D care.
Approval and access
Dapagliflozin’s EU/UK T1D indication was withdrawn by its manufacturer in October 2021; the UK communication explicitly says the removal is not due to any safety concern. Sotagliflozin’s European authorization was withdrawn in March 2022 at the holder’s request for commercial reasons. These reasons should not be replaced with speculation about company motives.12
Japan approved dapagliflozin as a T1D insulin adjunct in 2019.3 No class-wide Japanese approval for every SGLT2 drug was established in the sources reviewed here. Off-label use and reimbursement elsewhere differ from a licensed T1D indication.
September 2026 development check
Lexicon’s August 6 update moved the anticipated US T1D resubmission to Q4 2026, dependent on STENO1 collecting sufficient exposure and safety data. It also identifies the UAE and Bahrain sotagliflozin approvals as heart-failure indications. Neither is evidence of T1D approval. An NDA resubmission target is not a promised FDA decision date.6
What's next for this
- →Potential US sotagliflozin T1D NDA resubmission, dependent on STENO1 data · Q4 2026 company target
Sources
- [1]Forxiga (dapagliflozin) 5mg should no longer be used for the treatment of type 1 diabetes mellitus — Direct Healthcare Professional Communication · Regulatory decision · 2021-11-11 — Issued November 2021 (listed as first published 11 November 2021). The marketing-authorisation holder withdrew the type 1 diabetes indication for Forxiga 5mg across the EU and UK on 25 October 2021. The communication states the withdrawal was not prompted by a new safety signal. Diabetic ketoacidosis is a common (at least 1 in 100) adverse reaction in the type 1 studies of dapagliflozin.
EMA. Forxiga T1D safety communication.
- [2]Zynquista (sotagliflozin) — European Medicines Agency medicine overview · Regulatory decision · 2022-03-22 — Sotagliflozin was authorised in the EU on 26 April 2019 as an adjunct to insulin in adults with type 1 diabetes and a BMI of 27 or above who were inadequately controlled on insulin alone. The EU marketing authorisation was withdrawn on 22 March 2022 at the request of the marketing-authorisation holder, for commercial reasons.
EMA. Zynquista overview.
- [3]Forxiga approved in Japan for type-1 diabetes · Manufacturer · 2019-03-27 — Japan's Ministry of Health, Labour and Welfare approved Forxiga (dapagliflozin) in March 2019 as an oral adjunct to insulin in adults with type 1 diabetes. This approval remains in force.
AstraZeneca. Forxiga approved in Japan for T1D.
- [4]Lexicon Pharmaceuticals Provides a Business and Pipeline Update at the 44th Annual J.P. Morgan Healthcare Conference · Manufacturer · 2026-01-12 — Company guidance: Lexicon expects to resubmit the US sotagliflozin NDA for type 1 diabetes in 2026, with potential resubmission and approval in 2026, contingent on the independently run STENO1 study supplying the DKA-incidence and exposure data the FDA required. The release also states that licensee Viatris obtained regulatory approval for sotagliflozin in the United Arab Emirates, but does not say which indication that approval covers.
- [5]Dapagliflozin (Forxiga) is no longer to be used for type 1 diabetes · Open-source community · 2021-11-18 — Published November 2021 (listed as published 18 November 2021). Patient-facing explanation of the UK withdrawal, including the advice given to people with type 1 diabetes who were taking dapagliflozin at the time.
- [6]Lexicon second-quarter 2026 clinical update · Manufacturer · 2026-08-06
Lexicon. August 2026 clinical update.