Semaglutide May Significantly Reduce Systolic Blood Pressure in People with T2D

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Oral or subcutaneous semaglutide can significantly reduce systolic blood pressure in people with type 2 diabetes (T2D), according to findings from a recent systematic review and meta-analysis.¹

Across 29 randomized controlled trials (RCTs), semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), showed notable reductions in both glycated hemoglobin A1c (HbA1c) and body weight loss, but no significant impact on diastolic blood pressure.

“In terms of oral and subcutaneous formulations of semaglutide, changes in study design did not obviously alter the estimated therapeutic effect,” wrote the investigative team, led by Jia Cui, department of endocrinology, Chun’an First People’s Hospital.

Poor control of blood pressure is common in people with T2D, with hypertension occurring in approximately two-thirds of patients, making optimal blood pressure lowering crucial for disease management.² Semaglutide provides glucose-lowering effects in a glucose-dependent manner and does not increase hypoglycemia risk. The agent has been shown to reduce HbA1c, weight, and provide additional benefits, including blood pressure regulation and kidney function improvement.

However, Cui and colleagues noted the dearth of studies analyzing the impact of semaglutide on blood pressure as a primary outcome.¹ Their review assessed the findings of nearly 30 RCTs to determine the effect of semaglutide on blood pressure levels in people with T2D. The systematic review included a search of PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Library.

Investigators analyzed RCTs comparing oral or subcutaneous semaglutide with placebo or other antihyperglycemic agents in patients aged ≥18 years with T2D. The change from baseline in systolic and/or diastolic blood pressure was identified as the primary outcome for included RCTs, while data on changes in HbA1c and body weight were additionally extracted. Weighted mean differences and 95% confidence intervals were used to express meta-analysis results.

Cui and colleagues identified an initial 1848 unique citations and included 29 RCTs (n = 26,985) published between 2016 and 2023. A total of 10 trials (n = 9541) included once-daily oral semaglutide, 18 trials (n = 16,814) included once-weekly subcutaneous semaglutide, and 1 study (n = 630) assessed both oral and subcutaneous semaglutide.

Upon analysis, investigators found the mean change from baseline in systolic blood pressure was –2.31 mmHg (95% CI, –3.11 to –1.51) for semaglutide versus placebo. The effect of semaglutide on systolic blood pressure in individual studies ranged from –7.00 to 2.00 mmHg. Meanwhile, the mean difference in diastolic blood pressure was 0.009 mmHg (95% CI, -0.16 to 0.33) across all 29 RCTS, and did not reach statistical significance.

Compared to placebo, or other antihyperglycemic agents, including other GLP-1 RAs, semaglutide additionally led to a reduction in glycated HbA1c (-0.75% [95% CI, -0.92 to -0.58]) and body weight (-2.80 kg [95% CI, -3.51 to -2.08). The analysis revealed similar reductions in systolic blood pressure for both subcutaneous and oral administration of semaglutide. Patients treated with oral semaglutide showed a total reduction of –2.50 mmHg (95% CI, –3.48 to –1.53) in systolic blood pressure, while those treated with subcutaneous semaglutide showed a decrease of –2.36 mmHg (95% CI, –3.38 to –1.35).

In their summary, Cui and colleagues indicated the need for future literature to assess the blood pressure-lowering mechanisms of semaglutide. The team noted a greater understanding of these associations could ultimately benefit more people with diabetes.

“For diabetes patients with hypertension, the antihypertensive effect of semaglutide may be greater than the 2.31 mmHg in this paper, but the real-world effect has yet to be determined,” investigators wrote.

References

1. _{Wu W, Tong HM, Li YS, Cui J. The effect of semaglutide on blood pressure in patients with type-2 diabetes: a systematic review and meta-analysis. Endocrine. Published online December 15, 2023. doi:10.1007/s12020-023-03636-9}
2. _{Kim HJ, Kim KI. Blood Pressure Target in Type 2 Diabetes Mellitus. Diabetes Metab J. 2022;46(5):667-674. doi:10.4093/dmj.2022.0215}