Japan Study: DKA Risk With Dapagliflozin in Type 1 Diabetes

A study from Japan is offering important reassurance — with some important caveats — for people with Type 1 diabetes (T1DM) who take the SGLT2 inhibitor dapagliflozin (brand name: Farxiga). Researchers examined whether this popular blood sugar-lowering medication meaningfully raises the risk of a dangerous complication called diabetic ketoacidosis (DKA).

What Is DKA — and Why Does It Matter With SGLT2 Inhibitors?

Diabetic ketoacidosis is a life-threatening emergency where the body produces dangerously high levels of blood acids called ketones. It can occur even when blood sugar levels appear relatively normal — a phenomenon sometimes called "euglycemic DKA" — which makes it especially tricky to catch. SGLT2 inhibitors like dapagliflozin work by flushing excess glucose through the urine, and while effective, they have long carried an FDA warning about elevated DKA risk, particularly in people with T1DM.

What the Japanese Researchers Found

The research team at Japan Patient Safety and AstraZeneca K.K. in Osaka analyzed data from the JMDC Payer database, a large Japanese insurance claims database. They followed 327 insulin-treated T1DM patients who were newly prescribed dapagliflozin between March 2019 and March 2021, comparing them to 980 similar patients who did not take any SGLT2 inhibitor.

The DKA incidence rates were:

• Dapagliflozin group: 1.54 DKA events per 100 patient-years
• Control group (no SGLT2 inhibitor): 1.14 DKA events per 100 patient-years

The hazard ratio — a measure of relative risk — was 1.28, meaning roughly a 28% higher rate in the dapagliflozin group. However, the confidence interval ranged from 0.40 to 4.09, meaning the true difference could be negligible or even slightly protective. In statistical terms, this result was not significant, and the authors concluded there was no unexpected or meaningful increase in DKA risk.

Why an International Perspective Is Valuable for US Patients

Japan has one of the world's most meticulous pharmaceutical post-marketing surveillance systems, and Japanese T1DM patients tend to use insulin very carefully with close physician oversight. This real-world data from a different healthcare system — with different diets, body compositions, and clinical practices — helps confirm whether findings from US and European clinical trials hold up across diverse populations. When multiple countries reach similar conclusions, the evidence becomes more reliable for everyone.

How This Compares to US Guidelines

The FDA approved dapagliflozin as an adjunct to insulin for T1DM in 2019 but requires a black box warning about DKA risk. The American Diabetes Association (ADA) Standards of Care acknowledge that SGLT2 inhibitors can be considered in T1DM patients on insulin but emphasize careful patient selection, education about ketone monitoring, and sick-day rules. This Japanese study aligns with earlier clinical trial data — such as the DEPICT program — showing a modest but real DKA signal that requires vigilance rather than outright avoidance.

Why This Matters for US Patients

If you have Type 1 diabetes and your doctor has prescribed dapagliflozin alongside your insulin, this study offers measured reassurance: the absolute DKA risk increase appears small, and this finding is consistent with international data. That said, DKA remains a real risk. US patients should always:

• Monitor blood ketones regularly, not just blood sugar
• Know the signs of DKA: nausea, vomiting, abdominal pain, fruity breath
• Follow sick-day rules — consider pausing dapagliflozin when ill, fasting, or before surgery
• Never stop insulin without medical guidance

Talk with your endocrinologist about whether dapagliflozin is appropriate for your individual situation.

Source: Tamura, Kim, Takumi. "Incidence of Diabetic Ketoacidosis in Dapagliflozin-Treated Japanese Patients With Type 1 Diabetes Mellitus: An Observational Cohort Database Study." Pharmacoepidemiology and Drug Safety, 2026. DOI: 10.1002/pds.70294. PMID: 41449745.