Effects of Sodium Glucose Cotransporter 2 Inhibitors by Diabetes Status and Level of Albuminuria
Bibliographic record
Abstract
Importance: There is uncertainty about the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in participants with chronic kidney disease, with guidelines offering different strengths of recommendation based on diabetes status and urine albumin to creatinine ratio (UACR). Objective: To assess the relative and absolute effects of SGLT2 inhibitor use across efficacy and serious safety outcomes in participants stratified by diabetes status and UACR (≥200 mg/g or <200 mg/g). Data Sources and Study Selection: Included 8 randomized clinical trials that studied an SGLT2 inhibitor with a label indication for use in kidney disease and recorded longitudinal kidney outcomes and baseline data on albuminuria. Data Extraction and Synthesis: Data were combined using inverse variance-weighted meta-analysis; group-specific absolute effects were estimated by applying relevant relative risks to the event rates of the placebo groups. Main Outcomes and Measures: Assessed the effects of SGLT2 inhibitor use on clinical efficacy and safety outcomes. Heterogeneity by baseline level of UACR was assessed separately by diabetes status. Results: A total of 58 816 participants (mean age, 64 [SD, 10] years; 35% were female; 48 946 with diabetes and 9870 without diabetes) were included from trials comparing an SGLT2 inhibitor vs placebo. Allocation to an SGLT2 inhibitor produced a lower rate of kidney disease progression (33 vs 48 for placebo per 1000 patient-years; hazard ratio [HR], 0.65 [95% CI, 0.60-0.70] in those with diabetes and 32 vs 46 per 1000; HR, 0.74 [95% CI, 0.63-0.85] in those without diabetes), a lower rate of acute kidney injury (14 vs 18 per 1000 [HR, 0.77; 95% CI, 0.69-0.87] with diabetes and 13 vs 18 per 1000 [HR, 0.72; 95% CI, 0.56-0.92] without diabetes), a lower rate of any hospitalization (202 vs 231 per 1000 [HR, 0.90; 95% CI, 0.87-0.92] with diabetes and 203 vs 237 per 1000 [HR, 0.89; 95% CI, 0.83-0.95] without diabetes), and a lower rate of any death (42 vs 47 per 1000 [HR, 0.86; 95% CI, 0.80-0.91] with diabetes and 42 vs 48 per 1000 [HR, 0.91; 95% CI, 0.78-1.05] without diabetes). Diabetes-specific HRs were similar in participants (with a UACR ≥200 mg/g vs with a UACR <200 mg/g) considered separately. Higher absolute risk at a UACR of 200 mg/g or greater meant larger estimated absolute benefits on kidney disease progression were evident in this subgroup. Clear absolute benefits were evident for other efficacy outcomes, and particularly hospitalization, in participants with a UACR less than 200 mg/g. Net absolute benefits remained in the analyses of non-heart failure populations and when estimated glomerular filtration rate was less than 60 mL/min/1.73 m2. Conclusions and Relevance: Within the studied participants, there were clear absolute benefits of SGLT2 inhibitors on kidney, hospitalization, and mortality outcomes irrespective of diabetes status and level of UACR.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.056 | 0.131 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.029 |
| Bibliometrics | 0.004 | 0.004 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".