Cohort studyindependent cross-checkabstract checked I-ODD-104 standard review
Ketoacidosis on SGLT2 drugs often comes with only mildly raised sugar
Clinical characteristics and outcomes of diabetes-related ketoacidosis (DKA) in sodium-glucose co-transporter-2 inhibitor (SGLT2i) users with type 2 diabetes.
Overview
Sharma A et al.. Diabetes Obes Metab 2025 · PMID 40919651 · DOI 10.1111/dom.70098
Published cases had median glucose 10.6 mmol/L despite severe acidosis (pH 7.1).
Does the study support the specific claim? Yes · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Describe DKA in SGLT2 inhibitor users.
- How was the study done?
UK hospital cohort and review of published cases.
- How many people, animals or samples were studied?
1,060 admissions; 1,024 published cases.
- What was actually found?
Lower glucose and more acidosis in SGLT2i users; similar outcomes.
- How large was the observed effect?
Median glucose 10.6 mmol/L; 21% ICU.
- What do the results mean in everyday life?
Normal-looking sugar does not exclude ketoacidosis in people on these drugs.
- What are the study's limitations?
No incidence data.
- What does it say about Elawady's specific claim?
Supports the 'normal glucose' part.
- Do the results apply to Germany and Europe?
High.
- What can explicitly not be concluded from this study?
How often DKA occurs.
Scientific in-depth review
1. Full reference
- Authors
- Sharma A et al.
- Journal
- Diabetes Obes Metab
- Year
- 2025
- Identifier
- PMID 40919651 DOI 10.1111/dom.70098
- Verification
- verified – PubMed efetch 2026-10-26; Crossref works API 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
NIHR, Advanced Clinician Scientist Fellowship, ABCD and Sanofi DKA Collaborative Working Project Grant; authors declare no conflicts.
2. Research question
How does DKA in SGLT2 inhibitor users with type 2 diabetes differ from DKA in non-users?
3. Study design and population
- Study design
- Cohort study – Retrospective multicentre cohort (propensity-matched) plus systematic review and meta-summary of published cases
- Population
Adults with type 2 diabetes admitted with DKA in 18 UK hospitals; published case reports/series
- Country
UK (cohort); international (meta-summary)
- Period
April 2018-March 2024
- Sample size
1,060 DKA admissions (267 SGLT2i users, 793 non-users); 534 matched; 1,024 published cases from 247 studies
- Inclusion and exclusion criteria
DKA admissions managed with standardised protocols
4. Methods and endpoints
- Exposure / intervention
SGLT2 inhibitor use
- Comparator
Non-users with DKA
- Endpoints
Admission biochemistry, precipitants, duration of DKA, length of stay, ICU admission
- Statistical methods
Propensity score matching; descriptive meta-summary
5. Actual results
- Results
SGLT2i users had lower glucose, pH and bicarbonate than non-users; SGLT2i was the sole precipitant in 30.3%. Outcomes (DKA duration, length of stay) similar. Meta-summary of 1,024 cases: median pH 7.1, ketones 5.7 mmol/L, glucose 10.6 mmol/L (modest hyperglycaemia); DKA typically after 2 months of use; 21.1% needed intensive care.
- Absolute risks
Not applicable (case-based study; no denominators).
- Authors' conclusion
Despite lower admission glucose and more pronounced acidosis, outcomes were similar; better education on risk factors and prevention is warranted.
6. Strengths
- Standardised DKA protocols across 18 hospitals
- Large meta-summary of published cases
7. Weaknesses
- Case-based: cannot estimate incidence or causality
- Publication bias in case reports
8. Risk of bias
- Orienting tool
- ROBINS-E
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Selection of published cases; comparison restricted to people who already had DKA.
9. Assessment of the statistical interpretation
Descriptive; median glucose 10.6 mmol/L (about 191 mg/dL) shows that SGLT2i-associated DKA frequently presents with only modestly raised glucose.
10. Relevance to the specific claim
Directly supports the 'normal or low/near-normal glucose' element of the claim (euglycaemic or near-euglycaemic presentation).
11. Independent contrary findings
None on this point; the claim's 'low' glucose is rare (case reports only).
12. Transferability to Germany and Europe
High.
13. Overall methodological judgement
Supports the euglycaemic presentation as typical of SGLT2i-associated DKA.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | not applicable |
| Directness | direct |
| Reproducibility | partly replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Frequency of truly normoglycaemic or hypoglycaemic DKA.
15. Linked fact checks
- SGLT2 inhibitors such as dapagliflozin (Forxiga) can cause ketoacidosis, sometimes with normal or low blood glucose. – Studies supporting the claim