Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials

Baigent, Colin; Emberson, JonathanR.; Judge, Parminder; Landray, Martin J; Mayne, Kaitlin J.; Ng, Sarah; Preiss, David; Roddick, Alistair; Staplin, Natalie; Zhu, Doreen; Anker, Stefan D.; Bhatt, Deepak L.; Brueckmann, Martina; Butler, Javed; Cherney, David Z.I.; Green, Jennifer B.; Hauske, Sibylle J.; Haynes, Richard; Heerspink, Hiddo J.L.; Herrington, William G.; Inzucchi, Silvio E.; Jardine, Meg; Liu, Chih‐Chin; Mahaffey, Kenneth W.; McCausland, Finnian; McGuire, Darren K.; McMurray, John J.V.; Neal, Bruce; Neuen, Brendon L.; Packer, Milton; Perkovic, Vlado; Sabatine, Marc S.; Solomon, Scott D.; Vaduganathan, Muthiah; Wanner, Christoph; Wheeler, David C.; Wiviott, Stephen D.; Zannad, Faı̈ez

doi:10.1016/s0140-6736(22)02074-8

Cited by 416 publications

(321 citation statements)

References 58 publications

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“…In addition to the effects on glycemia, SGLT2i have shown to improve cardiovascular outcomes in patients with ASCVD and heart failure (HF) and be renoprotective in CKD patients (Table 1). 18,62–68 With labeled indications for T2DM, CKD, and now HF regardless of ventricular ejection fraction, SGLT2i have become attractive agents for many patient populations. These agents have also been shown to increase magnesium levels which could be beneficial to KTR with chronic hypomagnesemia and improving cardiovascular outcomes 69,70 .…”

Section: Resultsmentioning

confidence: 99%

“…61 In addition to the effects on glycemia, SGLT2i have shown to improve cardiovascular outcomes in patients with ASCVD and heart failure (HF) and be renoprotective in CKD patients (Table 1). 18,[62][63][64][65][66][67][68] With labeled indications for T2DM, CKD, and now HF regardless of ventricular ejection fraction, SGLT2i have become attractive agents for many patient populations.…”

Section: Overview In General Populationmentioning

confidence: 99%

“…The American Diabetes Association (ADA) guidelines recommend the use of GLP1RA and SGLT2i in patients with high risk of atherosclerotic cardiovascular disease 17 . In addition, SGLT2i have shown to have renoprotective effects as demonstrated in multiple large trials 18 . See Table 1 for details highlighting the use of these agents in the general population.…”

Section: Introductionmentioning

confidence: 99%

“…have shown to have renoprotective effects as demonstrated in multiple large trials. 18 See Table 1 for details highlighting the use of these agents in the general population.…”

Section: Introductionmentioning

confidence: 99%

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Sweet and simple as syrup: A review and guidance for use of novel antihyperglycemic agents for post‐transplant diabetes mellitus and type 2 diabetes mellitus after kidney transplantation

Lawrence

Chandran

Park

et al. 2023

Clinical Transplantation

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Uncontrolled type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) increase morbidity and mortality after kidney transplantation. Conventional strategies for diabetes management in this population include metformin, sulfonylureas, meglitinides and insulin. Limitations with these agents, as well as promising new antihyperglycemic agents, create a need and opportunity to explore additional options for transplant diabetes pharmacotherapy. Novel agents including sodium glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1RA), and dipeptidyl peptidase IV inhibitors (DPP4i) demonstrate great promise for T2DM management in the non-transplant population. Moreover, many of these agents possess renoprotective, cardiovascular, and/or weight loss benefits in addition to improved glucose control while having reduced risk of hypoglycemia compared with certain other conventional agents. This comprehensive review examines available literature evaluating the use of novel antihyperglycemic agents in kidney transplant recipients (KTR) with T2DM or PTDM. Formal grading of recommendations assessment, development, and evaluation (GRADE) system recommendations are provided to guide incorporation of these agents into post-transplant care. Available literature was evaluated to address the clinical questions of which agents provide greatest shortand long-term benefits, timing of novel antihyperglycemic therapy initiation after transplant, monitoring parameters for these antihyperglycemic agents, and concomitant antihyperglycemic agent and immunosuppression regimen management. Current experience with novel antihyperglycemic agents is primarily limited to single-center retrospective studies and case series. With ongoing use and increasing comfort, further and more robust research promises greater understanding of the role of these agents and place in therapy for kidney transplant recipients.

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Section: Resultsmentioning

confidence: 99%

Section: Overview In General Populationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…have shown to have renoprotective effects as demonstrated in multiple large trials. 18 See Table 1 for details highlighting the use of these agents in the general population.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sweet and simple as syrup: A review and guidance for use of novel antihyperglycemic agents for post‐transplant diabetes mellitus and type 2 diabetes mellitus after kidney transplantation

Lawrence

Chandran

Park

et al. 2023

Clinical Transplantation

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“…These benefits were verified by a trilogy of trials with kidney disease end points as the primary outcomes: CREDENCE, DAPA-CKD, and EMPA-KIDNEY ( 5 – 7 ). Together, these trials, meta-analyzed with the CVOTs and heart failure trials, found clear superiority of SGLT2 inhibitors compared with placebo, with a relative risk reduction of 40% for kidney disease progression in patients with or without type 2 diabetes ( 13 ).…”

Section: A History Of Sodium Glucose Cotransporter Inhibitorsmentioning

confidence: 99%

Digging deep into cells to find mechanisms of kidney protection by SGLT2 inhibitors

Tuttle

2023

Journal of Clinical Investigation

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Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction

Tavares,

Azevedo,

Rea-Neto

et al. 2024

JAMA

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ImportanceSodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown.ObjectiveTo determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction.Design, Setting, and ParticipantsMulticenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023.InterventionParticipants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first.Main Outcomes and MeasuresThe primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support–free days, ICU, and hospital stay, assessed using bayesian regression models.ResultsAmong 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group.Conclusion and RelevanceThe addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin.Trial RegistrationClinicalTrials.gov Identifier: NCT05558098

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Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials

Cited by 416 publications

References 58 publications

Sweet and simple as syrup: A review and guidance for use of novel antihyperglycemic agents for post‐transplant diabetes mellitus and type 2 diabetes mellitus after kidney transplantation

Sweet and simple as syrup: A review and guidance for use of novel antihyperglycemic agents for post‐transplant diabetes mellitus and type 2 diabetes mellitus after kidney transplantation

Digging deep into cells to find mechanisms of kidney protection by SGLT2 inhibitors

Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction

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