Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Objective To estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies. Design We conducted a systematic review and meta-analysis of randomised controlled trials (RCT). Six large databases were searched from inception to May 2018. Random effects models were used to estimate pooled relative risks (RRs). Intervention SGLT2 inhibitors, compared with placebo or active comparators. Primary outcomes Acute kidney injury (AKI), diabetic ketoacidosis (DKA), urinary tract infections (UTI), bone fractures and lower limb amputations. Results We screened 2418 citations of which 109 were included. Most studies included one of four SGLT2 inhibitors, dapagliflozin, canagliflozin, empagliflozin and ipragliflozin. When compared with placebo, SGLT2 inhibitors were found to be significantly protective against AKI (RR=0.59; 95% CI 0.39 to 0.89; I 2 =0.0%), while no difference was found for DKA (RR 0.66; 95% CI 0.30 to 1.45, I 2 =0.0%), UTI (RR 1.02; 95% CI 0.95 to 1.09, I 2 =0.0%) or bone fracture (RR 0.87; 95% CI 0.69 to 1.09, I 2 =1.3%). Three studies reported on amputation, with one finding a significant increase risk. No increased risk for either outcome was found when compared with active controls. Subgroup analysis did show an increased risk of UTI with dapagliflozin only (RR 1.21; 95% CI 1.02 to 1.43, I 2 =0.0%), but no other analysis supported an increased risk of AKI, DKA, UTI or fracture. Conclusions Current evidence from RCTs does not suggest an increased risk of harm with SGLT2 inhibitors as a class over placebo or active comparators with respect to AKI, DKA, UTI or fracture. However, wide CIs for many comparisons suggest limited precision, and therefore clinically important adverse events cannot be ruled out. Dapagliflozin, appears to independently increase the risk of UTI, although the mechanism for this intraclass variation in risk is unclear. PROSPERO registration number CRD42016038715.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.016 | 0.003 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it