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ADA 2021: Lowering of Blood Pressure and Pulse Rate by Switching from DPP-4 Inhibitor to Luseogliflozin in Patients with T2D and Hypertension

Aug 10, 2021
 
Editor: Steve Freed, R.PH., CDE

Author: Torré Anderson, II, Fourth Year Doctor of Pharmacy Candidate, Florida A&M University College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health 

Researchers investigate the changes in ambulatory blood pressure using the antidiabetic drug Luseogliflozin in patients with type 2 diabetes and hypertension.

Ambulatory blood pressure monitoring is a method that allows individuals to record their blood pressure over 24 hours. This method reveals irregular blood pressure variability, which is a risk for cardiovascular disease and mortality. Generally, nocturnal blood pressure decreases by 10% or more as compared to daytime blood pressure levels. Clinicians refer to this drop in nocturnal blood pressure as the “dipper” pattern. When nocturnal blood pressure doesn’t decrease or is higher than daytime blood pressure, it is referred to as the “riser” pattern. The “riser” pattern is associated with a higher risk of cardiovascular disease. Cardiovascular disease and stroke are critical issues in managing patients with type 2 diabetes. Clinicians have noted that effective treatment of Hypertension is limited because most patients usually have their blood pressure taken either in the clinic or at home daily. However, this may not be a good representation of a patient’s 24-hour blood pressure readings. Adequate maintenance of hypertension reduces their risk of developing cardiovascular issues. While the mechanism remains uncertain, sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been reported to reduce mortality associated with cardiovascular complications and decrease blood pressure. Dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used for diabetes management because of their safety regarding hypoglycemia, but the drug class does not affect cardiovascular mortality or blood pressure. 

 

The objective of this study was to investigate the changes in ambulatory blood pressure monitoring parameters between patients with type 2 diabetes and Hypertension who either continued DPP-4 inhibitors or switched to the SGLT-2 inhibitor Luseogliflozin. Researchers conducted a multicenter randomized open-label blind-endpoint parallel-group comparative study. The study’s primary endpoint assessed the mean change in nighttime systolic blood pressure (SBP) measured by ambulatory blood pressure monitoring. Secondary endpoints included mean change in diastolic blood pressure, daytime blood pressure, and laboratory parameters associated with glucose, lipid metabolism, and liver and renal function.

Researchers included participants in the study if they were Japanese patients with type 2 diabetes who were 20 years of age or older with a history of DPP-4 inhibitor use longer than four weeks, diagnosis of Hypertension, and HbA1c levels 6-9%. In addition, individuals were excluded from the study if they had a history of use or allergy with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, unstable retinopathy, renal or hepatic complications, pregnancy, or ketosis. Other exclusion criteria included a history of diabetic coma, severe infection, impaired insulin selection, BMI <22kg/m2, estimated glomerular filtration rate (eGFR) < 30mL/min, or night shift worker. Participants were randomized in a 1:1 ratio to either continue treatment of DPP-4 inhibitors or discontinue and initiate Luseogliflozin 2.5mg daily for eight weeks. Ambulatory blood pressure monitoring was conducted at the first visit for two days and then again at the third visit. Daytime and nighttime blood pressure recordings were self-recorded by participants. All ambulatory blood pressure results were collected using a TM-2433 device. Differences between the two groups were analyzed using the Mann-Whitney U-test for continuous variables and the Pearson’s χ² test for categorical data. 

Fifty-six patients were eligible for the study and were assessed. The average age of participants in the DPP-4 inhibitor and Luseogliflozin groups were 68 and 69 years of age, respectively. The majority of patients reported their duration of diabetes as 15 years or more. Dyslipidemia was the primary comorbid condition found in both treatment groups. Systolic blood pressure was significantly reduced by Luseogliflozin in both daytime and nighttime settings (P<0.01). Luseogliflozin reduced diastolic blood pressure considerably during the daytime setting (P<0.05). SGLT-2 inhibitor use improved overall blood pressure variability in the Luseogliflozin group. However, there were two participants in whom researchers observed higher blood pressure after treatment intervention. The researchers gathered that Luseogliflozin reduced nighttime blood pressure, pulse rate, and abnormal blood pressure variability due to sodium reduction. Luseogliflozin increased sodium excretion and urinary volume; the release of excess fluid improved albuminuria. 

Participants who switched from DPP-4 inhibitor therapy to Luseogliflozin had improved blood pressure variability and daytime and nighttime systolic blood pressure and pulse rate. The improvements observed could be associated with the cardiovascular benefits from SGLT-2 inhibitors. The study was limited with its cohort size, and thus results are not generalizable to a real-world setting. However, the strength of this study is that it is one of the first studies to compare the efficacy between Luseogliflozin and DPP-4 inhibitors on nocturnal hypertension. The study results provide the start of ongoing data on the effectiveness of Luseogloflozin in improving hypertension in patients living with type 2 diabetes. 

Practice Pearls:

  •  Luseogliflozin reduced diastolic blood pressure considerably during the daytime setting (P<0.05).
  • Participants who switched from DPP-4 inhibitor therapy to Luseogliflozin had improved blood pressure variability and daytime and nighttime systolic blood pressure and pulse rate.
  • The study was limited with its cohort size, and thus results are not generalizable to a real-world setting.

 

Kameda, R et al. (2021, June). Lowering of Blood Pressure and Pulse Rate by Switching from DPP-4 Inhibitor to Luseogliflozin in Patients with Type 2 Diabetes and Hypertension. American Diabetes Association. (requires ADA Symposium login.) Sapporo; Japan.

 

Torré Anderson, II, Fourth Year Doctor of Pharmacy Candidate, Florida A&M University College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health

 

 

 

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