Effects of SGLT2 inhibition on insulin use in CKD and type 2 diabetes: insights from the CREDENCE trial
Bibliographic record
Abstract
BACKGROUND: Insulin is a mainstay treatment for diabetes, but its use is associated with weight gain and hypoglycaemia. Data on the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on insulin use in people with chronic kidney disease (CKD) are limited. METHODS: We conducted a post hoc analysis of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial. Effects of canagliflozin versus placebo on insulin use (initiation, dose intensification, reduction and discontinuation) in people with CKD and type 2 diabetes were evaluated using Cox regression models. The primary outcome was insulin initiation or a >25% insulin dose intensification (in those not receiving and receiving insulin at baseline, respectively). Effects on kidney, cardiovascular and safety outcomes by baseline insulin use were also assessed. RESULTS: Among 4401 participants, 2884 (65.5%) were receiving insulin at baseline; these participants were more likely to have lower estimated glomerular filtration rate, higher albuminuria and a longer duration of diabetes (all P < .001). Over a median on-treatment period of 2.0 years, canagliflozin reduced the need for insulin initiation or a >25% dose intensification by 19% compared with placebo {hazard ratio [HR] 0.81 [95% confidence interval (CI) 0.71-0.93]}, irrespective of baseline kidney function or albuminuria (both P-interaction > .10). Sustained insulin dose reductions of >50% were achieved more frequently with canagliflozin than placebo [HR 1.49 (95% CI 1.15-1.91)], although no difference in insulin discontinuation was observed between treatment arms. Effects of canagliflozin on kidney, cardiovascular and safety outcomes were consistent regardless of baseline insulin use (all P-interaction > .05). CONCLUSIONS: In CKD and type 2 diabetes, canagliflozin reduces insulin use with consistent effects regardless of baseline kidney function. This supports the use of canagliflozin in people with CKD, not only for end-organ protection, but also to improve glycaemic control and reduce exposure to insulin and its associated adverse effects.
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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 | 0.007 | 0.012 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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".