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Benefits regardless of diabetes and urine protein
Sodium-glucose cotransporter 2 inhibitors reduced kidney worsening and hospitalizations across diabetes status and urine protein levels.
*Meta-analysis of randomized trials; Level 1a (OCEBM).

Citation

Staplin N, Roddick AJ, Neuen BL, et al; SMART-C. Effects of Sodium Glucose Cotransporter 2 Inhibitors by Diabetes Status and Level of Albuminuria: A Meta-Analysis. JAMA. 2026;335(3):220-232. doi:10.1001/jama.2025.20835

Background

These medicines are recommended for chronic kidney disease, but some guidelines give weaker recommendations for people without diabetes or with lower urine protein. This study pooled large trials to clarify benefits and serious harms across these groups.

Patients

58,816 adults from 8 randomized trials; 48,946 with diabetes and 9,870 without diabetes; grouped by urine albumin-to-creatinine ratio (200 mg/g or more vs less than 200 mg/g).

Intervention

Sodium-glucose cotransporter 2 inhibitor added to usual care.

Control

Placebo added to usual care.

Outcome

Kidney disease progression, acute kidney injury, any hospitalization, death, and key serious harms.

Follow-up Period

Approximately 1.6 to 3.3 years (varied by trial and outcome).

Results

Group Outcome Hazard ratio (95% confidence interval) Absolute change (events per 1000 patient-years) Number needed to treat or harm (1 year)
Diabetes Kidney disease progression 0.65 (0.60 to 0.70) 15 fewer Treat 67
No diabetes Kidney disease progression 0.74 (0.63 to 0.85) 14 fewer Treat 72
Diabetes Acute kidney injury 0.77 (0.69 to 0.87) 4 fewer Treat 250
No diabetes Acute kidney injury 0.72 (0.56 to 0.92) 5 fewer Treat 200
Diabetes Any hospitalization 0.90 (0.87 to 0.92) 29 fewer Treat 35
No diabetes Any hospitalization 0.89 (0.83 to 0.95) 34 fewer Treat 30
Diabetes Death from any cause 0.86 (0.80 to 0.91) 5 fewer Treat 200
Diabetes Ketoacidosis (serious harm) 2.29 (1.42 to 3.71) 0.5 more Harm 2000
Ketoacidosis is a dangerous buildup of acids in the blood.
Analyses were intention-to-treat. Relative benefits were similar in higher vs lower urine protein groups; kidney benefits were larger in absolute terms when urine protein was 200 mg/g or more.

Limitations

Not all eligible trials had urine protein data; subgroup tests may miss real differences; absolute benefit estimates reflect trial populations and were not adjusted for competing risks.

Funding

No industry funding for meta-analysis; included trials were industry-funded.

Clinical Application

For chronic kidney disease, consider these medicines even without diabetes or with lower urine protein, while counseling people with diabetes about rare ketoacidosis risk.

Top Journal Rankings - February 2026

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11679 abstracts scored across 7 criteria. Click any article to expand criterion scores.
1. 8.9
Aluminum-Adsorbed Vaccines and Chronic Diseases in Childhood : A Nationwide Cohort Study.
Overall: A very large nationwide cohort provides precise, patient-relevant evidence that cumulative aluminum exposure from early childhood vaccines is not associated with higher rates of autoimmune, atopic/allergic, or neurodevelopmental disorders, making it highly useful for primary-care counseling despite inherent observational limitations.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.5
Addresses a very common primary-care concern (vaccine safety counseling) in routine early-childhood immunization, with outcomes directly relevant to family medicine/pediatrics decision-making.
Validity, Bias Control & Precision 8.5
Very large nationwide registry-linked cohort with adjustment for confounders and tight confidence intervals for most outcomes; however, it remains observational (residual confounding possible) and diagnoses were not validated by chart review.
Patient-Oriented Outcomes 9.0
Outcomes are clinically meaningful diagnoses (autoimmune diseases, asthma/allergy conditions, ASD/ADHD) rather than laboratory surrogates, though severity, functional impact, and patient-reported outcomes are not described.
Magnitude of Net Benefit 8.0
Findings support no increased risk across 50 chronic disorders, with estimates near null and CIs often excluding moderate-to-large harm; benefit is primarily reassurance and risk communication rather than a direct therapeutic gain.
Implementability & Practicality 9.5
Results are easy to apply immediately in counseling and shared decision-making without new tests, monitoring, or workflow changes.
Practice-Changing Potential 9.0
High-quality large-scale safety evidence can meaningfully affect vaccine-hesitancy conversations and reinforce adherence to routine immunization, though it is less likely to alter immunization schedules already in place.
2. 8.8
Apixaban for Extended Treatment of Provoked Venous Thromboembolism.
Overall: A well-designed, double-blind RCT shows a large reduction in symptomatic recurrent VTE with extended low-dose apixaban and minimal major bleeding, making the findings highly actionable for outpatient anticoagulation decisions.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 8.0
VTE secondary prevention and decisions about extending anticoagulation commonly involve generalists in outpatient care, though some patients may be co-managed with hematology.
Validity, Bias Control & Precision 9.0
Double-blind randomized placebo-controlled design with 600 participants and a strong, precise effect estimate (HR 0.13; 95% CI 0.04–0.36) supports high internal validity.
Patient-Oriented Outcomes 9.0
Primary outcome (symptomatic recurrent VTE) and key safety outcomes (major bleeding, clinically relevant nonmajor bleeding, death) are directly patient-important.
Magnitude of Net Benefit 9.0
Large absolute reduction in recurrent symptomatic VTE (10.0% to 1.3% over 12 months) with very low major bleeding (1 vs 0) indicates substantial net benefit despite more nonmajor bleeding.
Implementability & Practicality 8.0
Apixaban 2.5 mg twice daily is a widely used oral anticoagulant and does not require INR monitoring, but bleeding-risk management and medication cost/access can be practical barriers.
Practice-Changing Potential 10.0
Provides clear randomized evidence for extended low-dose apixaban in a common gray-zone population (provoked VTE with enduring risk factors), with a large reduction in clinically important recurrence.
3. 8.5
Self-Collection for Cervical Cancer Screening in a Safety-Net Setting: The PRESTIS Randomized Clinical Trial.
Overall: A large pragmatic RCT in a safety-net system shows mailed HPV self-collection (with or without navigation) markedly increases cervical cancer screening participation versus reminder calls, with precise estimates and high real-world applicability, though outcomes are participation rather than clinical endpoints.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.5
Directly addresses a core primary-care preventive service (cervical cancer screening) in an outpatient safety-net population that generalists routinely manage.
Validity, Bias Control & Precision 8.5
Pragmatic randomized clinical trial with intent-to-screen analysis, large sample (~2474), and clear effect estimates with tight 95% CIs; only single-blinded and participation outcome is not fully blinded to participants.
Patient-Oriented Outcomes 6.5
Primary outcome is screening participation (process measure) rather than downstream patient outcomes (cancer incidence/mortality), though it is closely linked to prevention.
Magnitude of Net Benefit 9.0
Large absolute increases in screening participation at 6 months (≈+23.7% to +29.2% vs reminders alone) with no harms/burdens quantified in the abstract.
Implementability & Practicality 8.5
Mailed self-collection and navigation are operationally feasible in many systems, especially integrated safety-net settings, but require kit logistics, tracking, and navigator time.
Practice-Changing Potential 9.0
Provides strong randomized evidence in an underresourced setting that mailed self-collection substantially improves screening uptake over usual reminder outreach, supporting programmatic adoption where coverage is low.
4. 8.4
Increasing the uptake of long-acting reversible contraception through family practice: the Australian Contraceptive ChOice pRoject (ACCORd) cluster randomized controlled trial 3-year follow-up.
Overall: A primary-care cluster RCT follow-up showing sustained LARC use and fewer unintended pregnancies/abortions at 3 years suggests a clinically meaningful, implementable intervention, though reliance on survey follow-up and limited reporting of harms/precision temper certainty.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.5
Directly tests a family-practice–delivered contraception counseling/referral workflow and reports outcomes in typical primary-care patients over 3 years.
Validity, Bias Control & Precision 7.5
Cluster randomized trial with longitudinal 3-year follow-up and moderate sample size; however, outcomes rely on follow-up survey participation (75%), blinding is not described, and limited precision metrics are provided beyond p-values and some CIs.
Patient-Oriented Outcomes 9.0
Includes clearly patient-important outcomes (unintended pregnancies and abortions) plus satisfaction; not limited to contraceptive uptake alone.
Magnitude of Net Benefit 8.0
Shows meaningful absolute reductions in unintended pregnancy (3.1% vs 6.3%) and abortion (0.9% vs 3.6%) with supportive ORs and CIs; harms/burdens are not reported in the abstract, limiting full net-benefit assessment.
Implementability & Practicality 8.0
Intervention is pragmatic (online clinician training, structured counseling, and an online rapid-referral booking system), though it requires access to insertion clinics and referral infrastructure.
Practice-Changing Potential 8.5
A scalable primary-care intervention linked to fewer unintended pregnancies over 3 years is likely to influence practice, especially where LARC uptake is low and dedicated sexual health services are limited.
5. 8.3
Vaporized Nicotine Products for Smoking Cessation Among People Experiencing Social Disadvantage : A Randomized Clinical Trial.
Overall: A large randomized trial in a high-priority primary-care population shows a substantial, biochemically verified improvement in smoking cessation with VNPs versus NRT and fewer reported adverse events, supporting meaningful clinical impact with some real-world implementation constraints.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
Directly addresses a common primary-care problem (smoking cessation) in a high-need group, with an intervention a generalist could recommend and follow over time.
Validity, Bias Control & Precision 8.0
Large randomized trial (n=1045) with intention-to-treat analysis and blinded outcome ascertainment; open-label design and some loss to follow-up (82.9% completed) leave some residual risk of bias, but effect estimates are precise (credible interval reported).
Patient-Oriented Outcomes 9.0
Primary outcome is sustained smoking abstinence over 6 months with biochemical verification, which is strongly patient-important; adverse events were also reported.
Magnitude of Net Benefit 9.0
Large absolute benefit for verified abstinence (risk difference 18.7% with tight interval) and fewer self-reported adverse events in the VNP group, suggesting a favorable benefit–harm profile based on reported data.
Implementability & Practicality 7.0
Implementation is plausible (8-week provision plus text support), but real-world uptake may face access, regulatory, and workflow barriers compared with standard NRT depending on local policy and prescribing/dispensing pathways.
Practice-Changing Potential 8.0
The large, verified quit-rate improvement versus NRT in a socially disadvantaged population is likely to influence cessation strategies, though broader adoption may be tempered by local e-cigarette/VNP regulations and clinician comfort.
6. 8.2
Population Health Colorectal Cancer Screening Strategies in Adults Aged 45 to 49 Years: A Randomized Clinical Trial.
Overall: A large, precise RCT in primary care–aged adults shows default mailed FIT outreach achieves meaningfully higher screening completion than multiple active-choice approaches, making the findings highly applicable and potentially practice-shaping despite relying on a process outcome and limited reporting on harms/costs.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.5
Directly addresses how to increase colorectal cancer screening uptake in average-risk 45–49-year-old primary care patients using outreach approaches a health system/PCP network can deploy.
Validity, Bias Control & Precision 8.5
Large randomized clinical trial (n=20,509) with clear comparators and 6-month follow-up; effect estimates include tight 95% CIs, though blinding is not described and it is single health-system based.
Patient-Oriented Outcomes 6.0
Primary outcome is screening completion (a process measure); no downstream patient outcomes (cancer detection, stage, morbidity/mortality) or patient-reported outcomes are reported.
Magnitude of Net Benefit 7.0
Shows a sizable absolute difference in screening participation favoring usual care mailed FIT over active-choice strategies (about 9–12% absolute higher completion), but harms/burdens/costs of each strategy are not reported.
Implementability & Practicality 8.5
Interventions are pragmatic population-health outreach options (mailed FIT vs different “active choice” framings) that are plausibly scalable within many primary care systems, though operational details and costs are not provided.
Practice-Changing Potential 9.5
Provides high-quality evidence that default mailed FIT outreach outperforms several active-choice designs in a newly expanded screening age group, offering a clear, actionable takeaway for health systems.
7. 8.2
Daily Walking and Mortality in Racially and Socioeconomically Diverse U.S. Adults.
Overall: A large, long-followed cohort links faster daily walking to lower mortality with precise estimates and high real-world applicability, though causal inference is limited by observational self-reported exposure and unreported absolute benefits/harms.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 9.0
Directly informs a common primary-care counseling decision (walking/physical activity), studied in a large, racially and socioeconomically diverse U.S. outpatient population with major relevance to health equity.
Validity, Bias Control & Precision 6.5
Very large prospective cohort with long follow-up and many events yields precise estimates (n≈85,000; 26,862 deaths; narrow CIs), but observational design with baseline self-reported walking and potential residual confounding limits causal certainty.
Patient-Oriented Outcomes 10.0
Uses all-cause mortality (and cause-specific mortality) as outcomes, which are unequivocally patient-important.
Magnitude of Net Benefit 7.5
Association suggests clinically meaningful benefit for fast walking (HR 0.81 for 15 min/day) with minimal inherent harms/burdens; however, absolute risk reduction and adverse effects are not reported.
Implementability & Practicality 9.5
Fast walking is low-cost, broadly accessible, and feasible to recommend and monitor pragmatically in routine care without specialized equipment or medication management.
Practice-Changing Potential 6.5
Likely strengthens and refines existing activity counseling (emphasizing pace and small time doses, especially in disadvantaged groups), but as non-randomized evidence it is more reinforcing than definitively practice-changing.
8. 7.9
A phase 3, multicenter, randomized, placebo-controlled trial of monthly oral ibrexafungerp to reduce the incidence of recurrent vulvovaginal candidiasis.
Overall: This multicenter phase 3 randomized placebo-controlled trial shows a clinically meaningful reduction in recurrent vulvovaginal candidiasis with monthly oral ibrexafungerp and acceptable tolerability, making it relevant and potentially influential for outpatient management despite some reliance on mycologic outcomes and limited implementation details in the abstract.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 8.5
Recurrent vulvovaginal candidiasis is a common outpatient condition with quality-of-life impact, and monthly oral maintenance therapy is a decision point relevant to generalist care.
Validity, Bias Control & Precision 8.5
Phase 3 multicenter randomized placebo-controlled design with intent-to-treat results and reported RRs with 95% CIs supports credible estimates, though key operational details (e.g., blinding procedures/attrition) are not fully described in the abstract.
Patient-Oriented Outcomes 7.0
Outcomes include recurrence and a clinical success definition incorporating recurrence status; however, primary emphasis includes mycologic recurrence (more disease-oriented) and the symptom/QoL impact is not directly quantified.
Magnitude of Net Benefit 8.5
Absolute improvement was ~12% for both no mycologically proven recurrence (70.8% vs 58.5%) and clinical success (65.4% vs 53.1%) with sustained benefit in follow-up, while adverse events were mostly mild with no discontinuations in the treatment group.
Implementability & Practicality 7.5
A once-monthly oral regimen is practical, but the protocol requires an initial fluconazole induction and culture-confirmation/assessment steps that may add testing and workflow complexity in routine practice.
Practice-Changing Potential 7.5
Demonstrates a meaningful prophylactic option beyond standard azole strategies and could change management for recurrent cases, though real-world uptake will depend on factors not reported here (e.g., cost/access and longer-term safety).
9. 7.9
Pregnancy outcomes in type 2 diabetes: a systematic review and meta-analysis.
Overall: A large registered systematic review of observational cohorts reports markedly higher risks of major perinatal harms (including stillbirth and neonatal/perinatal mortality) in type 2 diabetes pregnancies compared with other comparator groups, making it highly clinically relevant, though limited by nonrandomized evidence and lack of intervention-specific, absolute-effect guidance.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 8.0
Pre-existing type 2 diabetes in pregnancy is common and increasingly encountered in outpatient/preconception and antenatal shared care; the outcomes compared (stillbirth, neonatal/perinatal mortality, congenital anomalies, growth outcomes) are directly relevant to counseling, risk stratification, and management planning.
Validity, Bias Control & Precision 7.5
Systematic review/meta-analysis with PROSPERO registration and a large evidence base (47 cohort studies; very large pooled sample ranges), but limited by observational designs with potential confounding and heterogeneity; confidence intervals are provided and are reasonably precise for several key estimates.
Patient-Oriented Outcomes 9.5
Primary outcomes are strongly patient-important (stillbirth, neonatal/perinatal mortality, congenital anomalies) with additional clinically meaningful neonatal size outcomes (LGA/SGA/macrosomia).
Magnitude of Net Benefit 7.5
Findings show substantially higher odds of serious adverse outcomes for T2D vs GDM and vs no diabetes (e.g., stillbirth OR 16.55 vs GDM; OR 7.27 vs non-diabetes; neonatal mortality OR 3.96 vs GDM), but results are comparative risk associations rather than effects of an intervention, and absolute risks are not reported in the abstract.
Implementability & Practicality 8.0
Implications are readily actionable as enhanced surveillance, preconception optimization, and counseling in routine care pathways; however, the abstract does not specify a concrete intervention or workflow, so practicality is inferred only at a general risk-awareness level.
Practice-Changing Potential 6.8
Likely to influence clinician counseling and prioritization of intensive management for T2D pregnancies by quantifying comparative risks, but it does not test a specific management strategy or provide absolute risk thresholds to directly change protocols on its own.
10. 7.8
The Mediterranean Diet for Irritable Bowel Syndrome : A Randomized Clinical Trial.
Overall: A pragmatic, short-term randomized trial suggests the Mediterranean diet can meaningfully improve IBS symptoms versus traditional dietary advice, with good primary-care relevance but limited long-term and harms data.
View 6 Criterion Scores
Primary-Care Relevance & Applicability 8.5
IBS is a common primary-care problem and dietary counseling is a typical first-line decision; the virtual, community-based UK sample increases real-world outpatient relevance.
Validity, Bias Control & Precision 7.0
Randomized noninferiority trial with modified intention-to-treat and reported CIs, but modest sample size, short 6-week follow-up, and key noninferiority details (e.g., margin, blinding) are not provided in the abstract.
Patient-Oriented Outcomes 8.0
Primary outcome is a validated symptom severity measure (IBS-SSS) and secondary outcomes include quality of life and psychological health, which are patient-important for IBS.
Magnitude of Net Benefit 8.0
Clinical response was higher with the Mediterranean diet (62% vs 42%; absolute difference 20% with CI 4–36%), suggesting a meaningful short-term benefit, though harms/burdens are not described in the abstract.
Implementability & Practicality 8.0
A Mediterranean diet is generally feasible to recommend and scale (including via virtual delivery) and likely less resource-intensive than low-FODMAP approaches, though it still requires dietary behavior change and support.
Practice-Changing Potential 7.5
Findings support a broadly acceptable first-line dietary option for IBS and could shift counseling, but limited duration and single-trial evidence temper immediate, definitive practice change.
Score Guide: 9-10 Exceptional 7-8 Strong 5-6 Moderate 3-4 Weak 1-2 Poor
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