Clinical Trials Digest

Category: T2DM

  • Intensive Blood Pressure Control in Type 2 Diabetes: BPROAD Trial Summary

    Intensive Blood Pressure Control in Type 2 Diabetes: BPROAD Trial Summary

    Background

    Hypertension is the most modifiable cardiovascular risk factor in patients with type 2 diabetes. Yet, the ideal target for systolic blood pressure (SBP) remains a point of contention. Previous trials like ACCORD showed neutral findings for intensive BP lowering, whereas SPRINT—excluding patients with diabetes—showed clear benefits. The BPROAD trial aimed to resolve this uncertainty by evaluating whether targeting an SBP <120 mm Hg confers cardiovascular benefits over the standard <140 mm Hg in patients with type 2 diabetes.

    Study Design

    • Trial Name: BPROAD (Blood Pressure Control Target in Diabetes)
    • ClinicalTrials.gov: NCT03808311
    • Journal: New England Journal of Medicine, March 2025
    • Study Period: 2019–2021
    • Sites: 145 centers across China
    • Design: Randomized, open-label, blinded endpoint assessment
    • Duration: Median 4.2 years follow-up

    Inclusion Criteria

    • Age ≥50 years
    • Type 2 diabetes
    • Elevated SBP: 130–180 mm Hg (treated) or ≥140 mm Hg (untreated)
    • Increased cardiovascular risk (prior CVD, CKD, or multiple risk factors)

    Interventions

    • Intensive group: SBP target <120 mm Hg
    • Standard group: SBP target <140 mm Hg
    • Antihypertensive regimens titrated per protocolized algorithms

    Primary Outcome

    Composite of:

    • Nonfatal stroke
    • Nonfatal myocardial infarction
    • Hospitalization or treatment for heart failure
    • Cardiovascular death

    Key Findings

    Blood Pressure Control

    Time Point Intensive SBP (mean) Standard SBP (mean)
    1 year 121.6 mm Hg 133.2 mm Hg

    Cardiovascular Outcomes

    Outcome Intensive Group Standard Group Hazard Ratio (95% CI) p-value
    Primary composite endpoint 1.65/100 PY 2.09/100 PY 0.79 (0.69–0.90) <0.001
    Fatal or nonfatal stroke 1.19/100 PY 1.50/100 PY 0.79 (0.67–0.92) —
    Heart failure hospitalization 0.13/100 PY 0.19/100 PY 0.66 (0.41–1.04) —
    Cardiovascular death 0.24/100 PY 0.32/100 PY 0.76 (0.55–1.06) —
    All-cause mortality 0.69/100 PY 0.73/100 PY 0.95 (0.77–1.17) —

    PY = person-years

    Safety Outcomes

    Adverse Event Intensive Group Standard Group Notable Findings
    Serious AEs 36.5% 36.3% No significant difference
    Symptomatic hypotension 0.1% <0.1% Slightly more frequent in intensive arm
    Hyperkalemia (>5.5 mmol/L) 2.8% 2.0% Statistically significant (p = 0.003)

    Conclusions

    Intensive blood pressure control (target SBP <120 mm Hg) significantly reduced the incidence of major cardiovascular events compared to standard control (<140 mm Hg) in patients with T2DM. Benefits were consistent across subgroups and came without an overall increase in serious adverse events—though hypotension and hyperkalemia were more common with intensive therapy.

    Clinical Perspective

    • Reinforces a shift toward more intensive BP targets in diabetes, aligning with SPRINT’s findings in non-diabetic populations.
    • Impacts guideline interpretations, potentially challenging the legacy of JNC 8.
    • Clinical implementation should weigh cardiovascular benefits against potential risks like electrolyte abnormalities and orthostatic events, especially in frail or elderly populations.

    Reference

    Bi Y, Li M, Liu Y, et al. Intensive Blood-Pressure Control in Patients with Type 2 Diabetes. N Engl J Med. 2025;392(12):1155-1167. doi:10.1056/NEJMoa2412006(https://doi.org/10.1056/NEJMoa2412006)

  • EMPA-REG OUTCOME

    EMPA-REG OUTCOME

    Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes

    Background and Overview

    T2DM, is a chronic disease that affects millions of people worldwide. It is characterized by high blood glucose levels due to insulin resistance or insufficient insulin production. T2DM can lead to CVD, and in severe cases, it can result in death. There are two primary treatment options for T2DM: pharmacological and non-pharmacological interventions. Pharmacological treatments involve the use of medications such as metformin, other oral medications, and insulin. Non-pharmacological interventions, on the other hand, entail lifestyle modifications such as weight management, exercise, and diet. Despite the availability of these treatments, managing T2DM can be challenging, and I can attest to this fact.

    One promising approach that has emerged in recent years is the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. These inhibitors prevent glucose reabsorption in the kidneys, leading to glucose excretion in the urine and reduced blood glucose levels. The SGLT2 inhibitors have shown significant promise in managing T2DM, and they should be considered a viable treatment option for our patients.

    Researchers designed the EMPA-REG OUTCOME trial to examine the effects of empagliflozin on CV morbidity and mortality in patients with type 2 diabetes at high CV risk. The clinical question being asked by the study in PICO is:

    • In patients with T2DM at high CV risk (population), does the addition of empagliflozin (intervention) to standard care (comparison) reduce CV morbidity and mortality (outcome)?
    • Journal: N Engl J Med
    • DOI: 10.1056/NEJMoa1504720
    • Impact factor: The NEJM is a highly reputable journal with a significant impact factor.

    Methods

    Study Design

    • Type of study: Randomized control trial
    • Prospective vs. retrospective: Prospective
    • Location, duration: 590 sites in 42 countries, median observation time of 3.1 years
    • Blinding: Double-blind
    • Control: Placebo-controlled
    • Main analysis type: Intention-to-treat

    Outcomes

    • Primary endpoint: Composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke
    • Secondary endpoint: Primary outcome plus hospitalization for unstable angina
    • Efficacy, safety, adverse events: Genital infection increased in the empagliflozin group, no increase in other adverse events

    Interventions

    • Study medications: Empagliflozin (10 mg or 25 mg) or placebo once daily
    • Ancillary treatments: Standard care for type 2 diabetes and cardiovascular risk factors

    Oversight

    • Study Population: N = 7020 patients treated
    • Experimental arm: n = 4687 patients
    • Placebo: n = 2333 patients

    Study Population

    • Recruitment: Adults with type 2 diabetes at high cardiovascular risk
    • Randomization method: Computer-generated random-sequence
    • Inclusion criteria: Type 2 diabetes, eGFR of at least 30 ml per minute per 1.73 m^2, established cardiovascular disease
    • Exclusion criteria: Specific glucose-lowering drugs, BMI of 45 or less

    Statistical Analysis

    • Power: At least 90%
    • Statistical tests used: Cox proportional-hazards model

    Results

    The author’s concluded that in patients with type 2 diabetes at high risk for cardiovascular events had a lower rate of primary composite cardiovascular outcome and death from any cause when empagliflozin was added to standard care.

    • Baseline characteristics: Similar across treatment and placebo groups
    • Comparison of treatment and control groups: Lower rates of the primary outcome in the empagliflozin group (10.5% vs. 12.1%, P = 0.04 for superiority)
    • Adverse events: Increased rate of genital infection but no increase in other adverse events

    Discussion and Conclusion

    Strengths/Limitations

    • Strengths: Well-designed RCT, large sample size, clear outcomes
    • Limitations: Limited to patients at high cardiovascular risk, short median observation time

    Conclusion

    • Interpretation of results: Empagliflozin shows promise in reducing cardiovascular morbidity and mortality in type 2 diabetes patients at high cardiovascular risk.
    • Bottom line: Empagliflozin may be a valuable addition to standard care for patients with type 2 diabetes at high cardiovascular risk.

    Citation

    Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128. doi:10.1056/NEJMoa1504720

    Glossary

    • T2DM: Type 2 diabetes mellitus
    • Empagliflozin (Jardiance): Selective inhibitor of sodium glucose cotransporter 2
    • eGFR: Estimated glomerular filtration rate or a measure of renal function
    • Cox proportional-hazards model: A statistical method for survival analysis