Hypertension and type 2 diabetes mellitus (T2DM) are common co-morbidities, with hypertension being twice as frequent in patients with T2DM as in those without. ^, Blood pressure (BP) control is of great importance in subjects with T2DM, to minimize the risk for cardiovascular and chronic kidney disease. High on-treatment BP levels also correlate with the incidence of major adverse cardiovascular outcomes and all-cause death; thus, adequate BP control should be placed at the epicenter.

Glucagon-like Peptide-1 receptor agonists (GLP-1 RAs), developed during the last decade, have revolutionized the treatment of T2DM and concomitant cardiovascular disease. Indeed, several recently published cardiovascular outcome trials have established their cardio-protective role in patients with T2DM. However, GLP-1 RAs do not significantly affect either systolic BP (SBP) or diastolic BP (DBP) under ambulatory condition.

Recently, novel dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RAs have been utilized in patients with T2DM, with a recent meta-analysis of relevant randomized controlled trials showing that this class improves glycemic control and induces greater body weight reduction than does placebo or active control. Of note, the SURPASS-2 trial demonstrated the superiority of tirzepatide, a dual GIP and GLP-1 RA, to semaglutide in terms of improvement of glycemic control and body weight loss.

Therefore, we sought to determine whether dual GIP and GLP-1 RAs have a significant effect on SBP and/or DBP in subjects with T2DM.

We searched PubMed and Cochrane Library databases for relevant published randomized controlled trials up to November 13, 2021. We assessed the change in office SBP and DBP with dual GIP and GLP-1 RAs compared with placebo or active comparator in subjects with T2DM.

Because we assessed only continuous variables, we calculated mean difference (MD), with 95% confidence interval (CI), after implementation of the Mantel-Haenszel random effects formula. Statistical heterogeneity among studies was assessed using I ² statistics. All analyses were performed at the 0.05 significance level and undertaken with RevMan 5.3 software.

We finally pooled data from 5 trials in a total of 5,060 patients with T2DM. We demonstrated that dual GIP/GLP-1 RAs compared with control induced a significant decrease in SBP by 3.6 mm Hg (MD −3.6, 95% CI −5.54 to −1.65, I ² = 83%, p = 0.0003), as shown in Figure 1 , along with a significant decrease in DBP by 1.29 mm Hg (MD −1.29, 95% CI −2.30 to −0.28, I ² = 74%, p = 0.01), as shown in Figure 2 .

Effect of dual GIP/GLP-1 RAs compared with control on systolic blood pressure.

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