The Effects of Combined Antihypertensive and Antidiabetic Therapies on Cardiovascular Outcomes: A Systematic Review...

Hypertension and diabetes frequently coexist, yet the net clinical impact of intentionally combining antihypertensive (AHTN) and antidiabetic (ADA) therapies on cardiovascular (CV) outcomes is uncertain. Here we quantified the effects of AHTN and ADA co-therapy on CV and blood pressure (BP)/heart rate (HR) outcomes.

The MEDLINE, Embase, and Scopus databases were searched from database inception through November 2025. Eligible studies were randomised controlled trials (RCTs) comparing combined AHTN+ADA versus AHTN or ADA alone and reporting CV events and/or (BP)/(HR) outcomes. Risk ratios (RRs) and mean differences (MDs) with 95% CIs were pooled using random-effects models. A prespecified exploratory analysis synthesised CV outcome trials of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus placebo.

Nine RCTs (n = 13 955 subjects) met inclusion criteria. Compared with AHTN alone, AHTN+ADA reduced composite CV events as defined in each trial, CV death, and HF hospitalisation. Combination therapy achieved modest but significant BP reductions (systolic -2.57 mmHg; diastolic -1.03 mmHg) without excess risk of hypotension, and HR effects were combination specific. Exploratory analysis of seven GLP-1 RA trials (n = ~56 000) showed reductions in composite CV events and CV death versus placebo, but no effect on HF hospitalisation.

AHTN+ADA co-therapy was associated with improved CV outcomes and modest BP reduction compared with monotherapy, with effects predominantly driven by SGLT2 inhibitor-based combinations. Exploratory evidence indicates that GLP-1 RAs provide complementary reductions in CV outcomes and mortality but not HF events. Together, these findings support phenotype-guided integration of ADA with guideline-directed AHTN in cardiometabolic disease.