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SGLT2 inhibitors

TL;DR — DAPA-CKD reduced its primary kidney/cardiovascular composite from 14.5% to 9.2% over median 2.4 years (HR 0.61, 95% CI 0.51–0.72; NNT 19) in albuminuric CKD with or without diabetes (Heerspink 2020, PMID 32970396). EMPA-KIDNEY reduced kidney progression or cardiovascular death from 16.9% to 13.1% over median 2.0 years (HR 0.72, 95% CI 0.64–0.82) across a broader CKD population (EMPA-KIDNEY Collaborative Group 2023, PMID 36331190). CREDENCE established kidney benefit in type 2 diabetes with albuminuric CKD on RAS blockade (HR 0.70, 95% CI 0.59–0.82) (Perkovic 2019, PMID 30990260). An early eGFR dip is followed by a slower chronic slope and should be interpreted as a treatment signature rather than automatic progression (Heerspink 2021, PMID 34619108) (EMPA-KIDNEY Collaborative Group 2024, PMID 38061371).

Trial populations

DAPA-CKD randomized 4,304 participants with eGFR 25–75 and uACR 200–5,000 mg/g; 2,906 of 4,304 (67.5%) had type 2 diabetes, so 32.5% did not (Heerspink 2020, PMID 32970396) (Heerspink 2021, PMID 34619108). EMPA-KIDNEY enrolled eGFR 20–<45 regardless of albuminuria or eGFR 45–<90 with uACR at least 200 (EMPA-KIDNEY Collaborative Group 2023, PMID 36331190).

Absolute and relative effects

Relative effects on clinical events were similar in participants with and without type 2 diabetes in both DAPA-CKD and EMPA-KIDNEY (Heerspink 2020, PMID 32970396) (EMPA-KIDNEY Collaborative Group 2023, PMID 36331190), but absolute benefit rises with baseline risk. The slope effect was not uniform: dapagliflozin's chronic-slope difference was larger in participants with type 2 diabetes than without (2.26 versus 1.29 mL/min/1.73 m²/year; p-interaction 0.0049), so consistency of relative event effects should not be read as identical biology (Heerspink 2021, PMID 34619108). Event definitions and follow-up differ, so cross-trial rankings are not justified.

eGFR slope

Dapagliflozin slowed total eGFR decline by 0.95 mL/min/1.73 m²/year versus placebo (Heerspink 2021, PMID 34619108). Empagliflozin caused a 2.12 mL/min/1.73 m² acute dip then halved chronic slope from −2.75 to −1.37 (EMPA-KIDNEY Collaborative Group 2024, PMID 38061371).

Low albuminuria

EMPA-KIDNEY slope analyses support biological benefit even with uACR below 30 mg/g, while clinical-event precision is lower because progression is slower (EMPA-KIDNEY Collaborative Group 2024, PMID 38061371).

Safety frame

Expected issues include volume depletion, genital infection and rare ketoacidosis; trial serious-adverse-event rates were broadly similar, but peri-illness interruption and phenotype matter (EMPA-KIDNEY Collaborative Group 2023, PMID 36331190).

Class boundary

The evidence supports a class kidney effect but individual labels, eGFR initiation limits and diabetes indications change over time and by regulator.

Pivotal trial comparison

Trial Population Primary result Interpretation
CREDENCE T2D, eGFR 30–<90, uACR >300–5000, RAS blockade 43.2 vs 61.2 events/1,000 patient-years; HR 0.70 (0.59–0.82) Dedicated diabetic albuminuric-CKD kidney-outcome evidence (Perkovic 2019, PMID 30990260)
DAPA-CKD eGFR 25–75, uACR 200–5000; with or without T2D 9.2% vs 14.5%; HR 0.61 (0.51–0.72); NNT 19 (15–27) Broadened benefit beyond diabetes (Heerspink 2020, PMID 32970396)
EMPA-KIDNEY eGFR 20–<45 regardless of uACR, or 45–<90 with uACR ≥200 13.1% vs 16.9%; HR 0.72 (0.64–0.82) Broadest GFR/albuminuria entry architecture (EMPA-KIDNEY Collaborative Group 2023, PMID 36331190)

The class effect, pooled

Individual trials cannot resolve whether diabetes status modifies benefit; the collaborative meta-analyses can. Pooling 13 placebo-controlled trials with 90,409 analysable participants (74,804 with diabetes, 15,605 without; trial-level mean baseline eGFR 37–85 mL/min/1.73 m²), SGLT2 inhibition reduced kidney disease progression — standardised to sustained ≥50% eGFR decline, sustained low eGFR, ESKD or death from kidney failure — by 37% (RR 0.63, 95% CI 0.58–0.69), with similar relative risks in participants with and without diabetes, and similar relative risks across primary kidney diagnoses within the four dedicated CKD trials (Nuffield Department of Population Health Renal Studies Group 2022, PMID 36351458).

The 2026 update resolves the albuminuria question that guidelines disagreed on. Across 8 trials of SGLT2 inhibitors with a kidney-disease label indication (58,816 participants; mean age 64, 35% female; 48,946 with and 9,870 without diabetes), kidney disease progression fell from 48 to 33 per 1,000 patient-years in diabetes (HR 0.65, 95% CI 0.60–0.70) and from 46 to 32 without diabetes (HR 0.74, 0.63–0.85). Diabetes-specific hazard ratios were similar in participants with uACR ≥200 mg/g and <200 mg/g considered separately, while absolute benefit was larger at higher uACR because event rates are higher (Staplin 2026, PMID 41202026). The same analysis found lower rates of acute kidney injury (14 vs 18 per 1,000; HR 0.77, 0.69–0.87 with diabetes; 13 vs 18; HR 0.72, 0.56–0.92 without), lower any-cause hospitalisation (HR 0.90, 0.87–0.92 and 0.89, 0.83–0.95) and lower all-cause death in the diabetes group (42 vs 47 per 1,000; HR 0.86, 0.80–0.91), with the non-diabetes death estimate not significant (HR 0.91, 0.78–1.05) (Staplin 2026, PMID 41202026).

The AKI result deserves emphasis because it is counter-intuitive: a drug that acutely lowers eGFR reduces recorded acute kidney injury. A network meta-analysis of 20 outcome trials (2,051 AKI events among 156,690 participants) had already found SGLT2 inhibitors associated with lower AKI risk than placebo (OR 0.76, 95% CI 0.66–0.88), lower than GLP-1 receptor agonists (OR 0.79, 0.65–0.97) and lower than DPP-4 inhibitors (OR 0.68, 0.54–0.86), with an 84% probability of being the safest of the three classes (Zhao 2020, PMID 33376101). The acute dip and AKI are therefore not the same phenomenon, and treating the dip as an injury signal is contradicted by the event data.

Safety, from pooled participant-level data

Pooling participant-level data from EMPA-REG OUTCOME, EMPEROR-Reduced, EMPEROR-Preserved and EMPA-KIDNEY at the 10 mg dose (10,472 on empagliflozin, 19,727 patient-years; 10,461 on placebo, 19,447 patient-years), serious, fatal and discontinuation-causing adverse events were similar between groups. Serious urinary tract infection and serious pyelonephritis or urosepsis rates were similar overall but higher in women on empagliflozin; serious genital infections were not increased; ketoacidosis and serious volume depletion were slightly increased; serious acute kidney injury was lower with empagliflozin; and there was no increase in severe hypoglycaemia, bone fracture or lower-limb amputation (Wanner 2024, PMID 38771475). The amputation and fracture signals that shaped early prescribing caution do not reproduce in this pooled dataset at this dose.

Head-to-head comparison of molecules exists only observationally. A target-trial emulation across three US claims databases compared 232,890 canagliflozin, 129,881 dapagliflozin and 295,043 empagliflozin initiators with type 2 diabetes, weighted on 129 confounders — the largest available comparison of individual agents, and the appropriate source for molecule-level rather than class-level questions (Shin 2025, PMID 39836397).

Beyond the CKD trials' entry criteria

Sotagliflozin (SGLT1/2). SCORED randomized 10,584 patients with type 2 diabetes and CKD but terminated early with incomplete endpoint adjudication. A secondary analysis using the complete laboratory dataset identified 223 events and found sotagliflozin reduced the composite of sustained ≥50% eGFR decline, eGFR <15, dialysis or transplant (87 events, 1.6% vs 136, 2.6%; HR 0.62, 95% CI 0.48–0.82; p < 0.001) and a cardiorenal composite adding cardiovascular or kidney death (239, 4.5% vs 306, 5.7%; HR 0.77, 0.65–0.91; p = 0.0023), with similar AKI incidence between arms (Sridhar 2024, PMID 38277468). This is an exploratory reanalysis of a prematurely stopped trial, so it supports rather than establishes a kidney indication.

Kidney transplant recipients. A randomized, double-blind, placebo-controlled physiology study in 52 transplant recipients (mean eGFR 68.2 ± 24.4 mL/min/1.73 m², 57% with type 2 diabetes) found dapagliflozin did not lower systolic blood pressure at 1 or 12 weeks but reduced mean arterial pressure at 1 week by 3.9 mmHg (95% CI −7.5 to −0.2) and reduced iohexol-measured GFR by 4.2 mL/min/1.73 m² (95% CI −7.14 to −1.24) at 1 week, with good tolerability (Sridhar 2026, PMID 41385300). A later 208-person, 12-month randomized trial in chronic allograft dysfunction found no eGFR benefit, but lower proteinuria, blood pressure and weight (David-Neto 2026, PMID 42102257). DEAK is recruiting 330 de novo recipients for a three-year chronic-eGFR-slope endpoint (Kongerud 2026, PMID 42315275; NCT05788276). Hard graft-failure, cardiovascular and mortality effects remain untested.

Cost-effectiveness

A lifetime Markov model built on DAPA-CKD projected that dapagliflozin adds 1.7 years (95% CrI 0.8–2.4) in the eGFR 15–89 range and 1.7 undiscounted life-years (0.7–2.5), yielding discounted QALY gains of 0.82 (0.38–1.18) to 1.00 (0.46–1.41) and ICERs of $8,280 (UK), $17,623 (Germany) and $11,687 (Spain) against willingness-to-pay thresholds of $27,510 and $35,503 per QALY (McEwan 2022, PMID 36323444). Even at branded prices the class was comfortably cost-effective in three European systems; the constraint on population benefit is prescribing rate, not price.

Question Best pooled answer Source
Does diabetes status modify relative kidney benefit? No: RR 0.63 (0.58–0.69) overall, similar with and without diabetes across 13 trials, n=90,409 Nuffield Renal Studies Group 2022, PMID 36351458
Does albuminuria below 200 mg/g abolish benefit? No: diabetes-specific HRs similar above and below 200 mg/g; absolute benefit larger above Staplin 2026, PMID 41202026
Do these drugs cause AKI? No: AKI reduced (HR 0.77 with diabetes, 0.72 without); lowest AKI risk of three drug classes Staplin 2026, PMID 41202026; Zhao 2020, PMID 33376101
Amputation and fracture risk? Not increased in pooled participant-level data at 10 mg empagliflozin Wanner 2024, PMID 38771475
Value for money? ICER $8,280–$17,623/QALY in UK, Germany, Spain McEwan 2022, PMID 36323444

A mechanistic side-effect that did not become a clinical one

Hyperuricaemia and gout are common in CKD, and SGLT2 inhibitors are uricosuric — an attractive secondary benefit. EMPA-KIDNEY tested it prospectively. Among 6,609 randomized participants (baseline mean serum uric acid 431 ± 114 µmol/L) followed a median 2 years, with uric acid measured at randomisation and at 2 and 18 months, empagliflozin produced a study-average between-group difference in serum uric acid of −25.6 µmol/L (95% CI −30.3 to −21.0), with larger effects at higher eGFR (trend p < 0.001) and in participants without diabetes (heterogeneity p < 0.001).

That biochemical effect did not translate. Participant-reported gout events were not significantly reduced: HR 0.87 (95% CI 0.74–1.02) for the 595 first events and 0.86 (0.72–1.03) for the 869 total events, with similar hazard ratios for a post-hoc composite of new urate-lowering therapy or colchicine initiation and across subgroups defined by diabetes and eGFR. Effects on the primary outcome and on kidney disease progression were similar regardless of baseline uric acid (Mayne 2025, PMID 39277784).

Two conclusions follow. A −25.6 µmol/L urate reduction is real but modest — roughly 6% of baseline — and is not enough to prevent gout, so SGLT2 inhibition should not be selected for that purpose. And the absence of effect modification by baseline uric acid is a further piece of evidence against the urate hypothesis discussed on the pathophysiology page: if urate drove progression, the kidney benefit should have been larger in those with the highest baseline levels.

Decision and interpretation matrix

Dimension Question Guardrail
Diagnostic axis Cause + G category + A category Avoid treating eGFR as the diagnosis
Time axis Chronicity and trajectory Separate acute change from persistent disease
Risk axis Kidney failure + cardiovascular events + death Show competing events
Treatment axis Eligibility, absolute benefit, harm, burden Do not rank drugs by relative effect alone
Measurement axis Assay, equation, repeatability State what was actually measured
Equity axis Testing, referral, access, affordability Audit downstream care, not labels only
Patient axis Symptoms, function, life participation Include outcomes patients prioritize
Evidence axis RCT, cohort, model, guideline Do not collapse designs

Evidence ledger

This ledger makes the page’s evidentiary mix inspectable. It does not imply that every source answers every question.

PMID Record used Role and boundary
32970396 Dapagliflozin in Patients with Chronic Kidney Disease. (Heerspink 2020, PMID 32970396) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
36331190 Empagliflozin in Patients with Chronic Kidney Disease. (EMPA-KIDNEY Collaborative Group 2023, PMID 36331190) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
30990260 Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. (Perkovic 2019, PMID 30990260) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
34619108 Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. (Heerspink 2021, PMID 34619108) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
38061371 Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the EMPA-KIDNEY trial. (EMPA-KIDNEY Collaborative Group 2024, PMID 38061371) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
38490803 KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. (KDIGO CKD Work Group 2024, PMID 38490803) Guideline or commentary; recommendation evidence depends on its review.
38519239 Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. (Levin 2024, PMID 38519239) Guideline or commentary; recommendation evidence depends on its review.
11565518 Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. (Brenner 2001, PMID 11565518) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
11565517 Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. (Lewis 2001, PMID 11565517) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
11565519 The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. (Parving 2001, PMID 11565519) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
18707986 Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk: the ONTARGET study. (Mann 2008, PMID 18707986) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
24206457 Combined angiotensin inhibition for the treatment of diabetic nephropathy. (Fried 2013, PMID 24206457) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
33264825 Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. (Bakris 2020, PMID 33264825) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
35023547 Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. (Agarwal 2022, PMID 35023547) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
38785209 Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. (Perkovic 2024, PMID 38785209) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
38914124 Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial. (Mann 2024, PMID 38914124) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
37952217 Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria. (Neuen 2024, PMID 37952217) Modelled projection; the estimate follows from the model inputs and assumptions, not from observed randomized follow-up.
30697905 SGLT2 inhibitors and cardiovascular, renal and safety outcomes in T2D and CKD: meta-analysis. (Toyama 2019, PMID 30697905) Synthesis; heterogeneity and included-study definitions constrain transport.
36316605 SGLT2 inhibitors in advanced CKD: systematic review and meta-analysis. (Cao 2023, PMID 36316605) Synthesis; heterogeneity and included-study definitions constrain transport.
36927680 Finerenone outcomes in stage 4 CKD and type 2 diabetes. (Sarafidis 2023, PMID 36927680) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
36272755 Executive summary of KDIGO 2022 Diabetes Management in CKD guideline. (Rossing 2022, PMID 36272755) Guideline or commentary; recommendation evidence depends on its review.
33637203 Executive summary of KDIGO 2021 Blood Pressure in CKD guideline. (Cheung 2021, PMID 33637203) Guideline or commentary; recommendation evidence depends on its review.
31533906 Patiromer to enable spironolactone in resistant hypertension and CKD: AMBER. (Agarwal 2019, PMID 31533906) Intervention study; eligibility, comparator, endpoint and follow-up bound inference.
40542996 Novel potassium binders, hyperkalemia and RAAS inhibitor optimization: meta-analysis. (Huang 2025, PMID 40542996) Synthesis; heterogeneity and included-study definitions constrain transport.
32061315 Global, regional, and national burden of chronic kidney disease, 1990-2017. (GBD CKD Collaboration 2020, PMID 32061315) Modelled projection; the estimate follows from the model inputs and assumptions, not from observed randomized follow-up.

What can and cannot be concluded

  • Risk associations do not by themselves establish that changing the marker changes risk.
  • A relative effect must be paired with baseline risk, follow-up and the exact endpoint.
  • Albuminuria, acute eGFR change, chronic eGFR slope and kidney failure are not interchangeable.
  • Subgroup consistency is not evidence that every subgroup had adequate power.
  • Guideline recommendations combine evidence with values, feasibility, cost and service capacity.
  • Older adults require competing-mortality and treatment-burden framing.
  • Dialysis and transplantation comparisons are vulnerable to eligibility and immortal-time bias.
  • Modelled lifetime benefit is not a randomized observed benefit.
  • A biochemical response without a patient-important outcome remains a surrogate result.
  • This page is research synthesis, not individualized medical advice.

Research-design checklist

  • Define CKD cause, G category, A category and chronicity at baseline.
  • Report the creatinine or cystatin C equation and laboratory calibration.
  • Prespecify acute and chronic eGFR slopes when haemodynamic effects are expected.
  • Keep sustained GFR decline, kidney failure and replacement therapy separable.
  • Report absolute event risks, follow-up and confidence intervals with relative effects.
  • Treat death as a competing event where it can preclude kidney failure.
  • Measure hyperkalaemia, acute kidney injury and treatment discontinuation consistently.
  • Include symptoms, function, life participation and treatment burden.
  • Describe background RAS, SGLT2, MRA and GLP-1 therapy explicitly.
  • Prespecify albuminuria and cause strata without over-reading underpowered interactions.
  • Record screening, prescribing, persistence and monitoring as separate implementation steps.
  • Report representation, access and affordability variables needed for equity analysis.

Open questions

  • What is the absolute clinical-event benefit of SGLT2 inhibition at uACR below 30 mg/g? The relative chronic-slope reduction was largest in that stratum precisely because progression is slowest, so hard-event precision is lowest where relative benefit looks greatest (EMPA-KIDNEY Collaborative Group 2024, PMID 38061371). → OQ-3
  • Why was the chronic-slope benefit larger with diabetes than without in DAPA-CKD (2.26 vs 1.29 mL/min/1.73 m²/year) when clinical-event effects looked similar (Heerspink 2021, PMID 34619108)?
  • How should the class be used below the eGFR entry limits of the pivotal trials, where evidence is extrapolated rather than observed?

  • Can the acute eGFR dip be used prospectively as a treatment-response signature rather than interpreted retrospectively (Heerspink 2021, PMID 34619108) (EMPA-KIDNEY Collaborative Group 2024, PMID 38061371)? → OQ-19

  • Why does a drug that acutely lowers eGFR reduce recorded acute kidney injury (HR 0.77 with diabetes, 0.72 without) (Staplin 2026, PMID 41202026) (Zhao 2020, PMID 33376101)? The mechanism linking the haemodynamic dip to fewer AKI events is unestablished.

  • Do SGLT2 inhibitors improve patient-important outcomes in kidney transplant recipients? Randomized studies now include 52-person physiology and 208-person 12-month surrogate-endpoint trials (Sridhar 2026, PMID 41385300; David-Neto 2026, PMID 42102257), while the 330-person DEAK trial uses chronic eGFR slope (Kongerud 2026, PMID 42315275); none is powered for graft failure, cardiovascular events or mortality.
  • Is the sotagliflozin kidney benefit real? SCORED's kidney composite became significant (HR 0.62, 0.48–0.82) only in an exploratory reanalysis after early termination and suspended adjudication (Sridhar 2024, PMID 38277468).

  • Do individual SGLT2 inhibitors differ in effectiveness or safety? Only observational target-trial emulation addresses this; no head-to-head randomized comparison exists (Shin 2025, PMID 39836397).

  • Why does a −25.6 µmol/L reduction in serum uric acid not reduce gout events (HR 0.87, 0.74–1.02) (Mayne 2025, PMID 39277784) — is the effect simply too small, or is the CKD gout phenotype driven by something other than serum urate level?

  • The kidney benefit of empagliflozin was independent of baseline uric acid (Mayne 2025, PMID 39277784), which argues against urate mediation — does the same independence hold for the other kidney-protective classes?

References

  1. Heerspink et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020;383(15):1436-1446. PMID 32970396
  2. EMPA-KIDNEY Collaborative Group et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023;388(2):117-127. PMID 36331190
  3. Perkovic et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019;380(24):2295-2306. PMID 30990260
  4. Heerspink et al. Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021;9(11):743-754. PMID 34619108
  5. EMPA-KIDNEY Collaborative Group et al. Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the EMPA-KIDNEY trial. Lancet Diabetes Endocrinol. 2024;12(1):39-50. PMID 38061371
  6. KDIGO CKD Work Group et al. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117-S314. PMID 38490803
  7. Levin et al. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns. Kidney Int. 2024;105(4):684-701. PMID 38519239
  8. Brenner et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861-869. PMID 11565518
  9. Lewis et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345(12):851-860. PMID 11565517
  10. Parving et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345(12):870-878. PMID 11565519
  11. Mann et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk: the ONTARGET study. Lancet. 2008;372(9638):547-553. PMID 18707986
  12. Fried et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013;369(20):1892-1903. PMID 24206457
  13. Bakris et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020;383(23):2219-2229. PMID 33264825
  14. Agarwal et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43(6):474-484. PMID 35023547
  15. Perkovic et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024;391(2):109-121. PMID 38785209
  16. Mann et al. Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial. Nat Med. 2024;30(10):2849-2856. PMID 38914124
  17. Neuen et al. Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria. Circulation. 2024;149(6):450-462. PMID 37952217
  18. Toyama et al. SGLT2 inhibitors and cardiovascular, renal and safety outcomes in T2D and CKD: meta-analysis. Diabetes Obes Metab. 2019;21(5):1237-1250. PMID 30697905
  19. Cao H, et al. Effects of sodium-glucose co-transporter-2 inhibitors on kidney, cardiovascular, and safety outcomes in patients with advanced chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol. 2023;60(3):325-335. PMID 36316605
  20. Sarafidis et al. Finerenone outcomes in stage 4 CKD and type 2 diabetes. Clin J Am Soc Nephrol. 2023;18(5):602-612. PMID 36927680
  21. Rossing et al. Executive summary of KDIGO 2022 Diabetes Management in CKD guideline. Kidney Int. 2022;102(5):990-999. PMID 36272755
  22. Cheung et al. Executive summary of KDIGO 2021 Blood Pressure in CKD guideline. Kidney Int. 2021;99(3):559-569. PMID 33637203
  23. Agarwal et al. Patiromer to enable spironolactone in resistant hypertension and CKD: AMBER. Lancet. 2019;394(10208):1540-1550. PMID 31533906
  24. Huang et al. Novel potassium binders, hyperkalemia and RAAS inhibitor optimization: meta-analysis. Drugs. 2025;85(8):1013-1031. PMID 40542996
  25. GBD CKD Collaboration et al. Global, regional, and national burden of chronic kidney disease, 1990-2017. Lancet. 2020;395(10225):709-733. PMID 32061315
  26. Nuffield Department of Population Health Renal Studies Group. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022;400(10365):1788-1801. PMID 36351458
  27. Staplin N, et al. Effects of Sodium Glucose Cotransporter 2 Inhibitors by Diabetes Status and Level of Albuminuria: A Meta-Analysis. JAMA. 2026;335(3):220-232. PMID 41202026
  28. Zhao M, et al. Network Meta-Analysis of Novel Glucose-Lowering Drugs on Risk of Acute Kidney Injury. Clin J Am Soc Nephrol. 2020;16(1):70-78. PMID 33376101
  29. Wanner C, et al. Safety of Empagliflozin: An Individual Participant-Level Data Meta-Analysis from Four Large Trials. Adv Ther. 2024;41(7):2826-2844. PMID 38771475
  30. Shin H, et al. Comparative Effectiveness of Individual Sodium-Glucose Cotransporter 2 Inhibitors. JAMA Intern Med. 2025;185(3):302-313. PMID 39836397
  31. Sridhar VS, et al. Sotagliflozin and Kidney Outcomes, Kidney Function, and Albuminuria in Type 2 Diabetes and CKD: A Secondary Analysis of the SCORED Trial. Clin J Am Soc Nephrol. 2024;19(5):557-564. PMID 38277468
  32. Sridhar VS, et al. Efficacy, Mechanisms, and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Kidney Transplant Recipients: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin J Am Soc Nephrol. 2026;21(4):664-679. PMID 41385300
  33. McEwan P, et al. Cost-Effectiveness of Dapagliflozin as a Treatment for Chronic Kidney Disease: A Health-Economic Analysis of DAPA-CKD. Clin J Am Soc Nephrol. 2022;17(12):1730-1741. PMID 36323444
  34. Mayne KJ, et al. Empagliflozin lowers serum uric acid in chronic kidney disease: exploratory analyses from the EMPA-KIDNEY trial. Nephrol Dial Transplant. 2025;40(4):720-730. PMID 39277784
  35. David-Neto E, et al. The Effect of Adding Dapagliflozin on Chronic Renal Allograft Dysfunction: A Randomized, Prospective, Double-blind, Placebo-controlled Trial. Transplantation. 2026;110(7):e1527-e1538. PMID 42102257
  36. Kongerud IC, et al. Can sodium-glucose cotransporter 2 (SGLT2) inhibition preserve renal structure and function in de novo kidney transplant recipients? Protocol for a randomised, double-blind, placebo-controlled trial assessing the efficacy of dapagliflozin on kidney structure, function and safety in kidney transplant recipients in Norway-the DEAK study. BMJ Open. 2026;16(6):e117263. PMID 42315275