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A Possible Role for SGLT-2 Inhibitors in Blood Pressure Control

New studies indicate potential class effect in reducing hypertension.

As the appropriateness of intensive blood pressure control targets for diabetic patients becomes a growing topic of discussion, new studies suggest there may be reason to consider SGLT-2 inhibitors in blood pressure control. Diabetes and its many complications have become a great concern in the American healthcare system, with approximately 29.1 million Americans having diabetes in 2012. The number of annual newly diagnosed cases of diabetes has tripled from 493,000 in 1980 to more than 1.4 million in 2014, according to the CDC. While the rates of diabetes peaked in 2009 at 1.7 million cases per year, and have since declined to 1.4 million in 2014, patients and healthcare providers should still be ever vigilant and adopt good health practices to prevent diabetes.

Those with diabetes suffer from many complications and chronic comorbidities. In 2011, there were 282,000 emergency room visits for adults aged 18 or older with hypoglycemia associated with diabetes. Studies found that roughly 71% of diabetic patients have blood pressure greater than or equal to 140/90 mmHg, or used prescription drugs to lower their blood pressure. Diabetics have an increased risk of cardiovascular disease, heart attack, stroke, blindness, kidney disease, and amputations. Monitoring and controlling the disease is an important step in preventing these risks.

There are many options and treatments for diabetes. Those with diabetes are first recommended to make lifestyle modifications and increase their physical activity to help control their disease. If lifestyle modification does not adequately control their disease, patients are put on drug therapy. According to the ADA guidelines, metformin is first-line therapy for patients whose glycemic control goals are not met. If metformin still does not control the patient’s blood glucose, additional oral therapy can be added before moving onto insulin. There are many different choices for a second line or third line therapy for metformin. Sodium glucose cotransporter (SGLT-2) inhibitors are the newest addition to diabetes care, and more studies are showing additional benefits beyond glycemic control.

SGLT-2 are proteins in the kidney that are responsible for 90% of glucose reabsorption. SGLT-2 inhibitors work by blocking the reabsorption of glucose, resulting in increasing glucose excretion, and ultimately lowering blood glucose levels. New studies are coming out showing evidence of decreases in blood pressure when using SGLT-2.

Empagliflozin

A randomized double-blind placebo controlled study looked at patients with type 2 diabetes and hypertension on empagliflozin. The study recruited 825 participants with type 2 diabetes and hypertension greater than or equal to 160/100 mmHg who were put on empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily for 12 weeks. The results from the study showed that 10 mg versus placebo showed a -3.44 mmHg SBP drop and in 25 mg versus placebo showed a -4.16 mmHg SBP drop (P < 0.001). When looking at DBP, 10 mg versus placebo showed a -1.36 mmHg DBP drop and in 25 mg versus placebo showed a -1.72 mmHg DBP drop (P < 0.001). The adjusted change from HbA1c levels in empagliflozin versus placebo showed an average of -0.62% in the 10 mg group and -0.65% in the 25 mg group. The study provided evidence that empagliflozin is associated with lowering blood pressure and HbA1c levels versus placebo in patients with type 2 diabetes and hypertension.

Dapagliflozin

A randomized phase 3 study looked at the glycemic control and systolic blood pressure in type 2 diabetes patients on dapagliflozin. There are 613 patients randomized to receive dapagliflozin 10 mg (n=302) or placebo (n=311) once daily for 12 weeks. The primary outcomes were measured by change in baseline to week 12 of SBP and HbA1c levels. At the end of 12 weeks, the study found that dapagliflozin patients showed a significant reduction in HbA1c and SBP over placebo group. The study found a reduction of HbA1c of -0.6% vs -0.1% and a reduction of SBP -10.4 mmHg vs -7.3 mmHg when comparing dapagliflozin vs placebo, respectively.

The results from these two studies show that SGLT-2 inhibitors control blood glucose and help with weight loss, but also help reduce blood pressure, which can lead to cardiovascular benefits. Though the study looked at two different individual drugs, the results suggest that the SGLT-2 drug class as a whole can confer blood pressure benefits. Hypertension is prevalent in diabetic patients and SGLT-2 inhibitors provide patients with benefits to both diseases.

Practice Pearls:

  • SGLT-2 inhibitors are the newest class of antidiabetic medication that control blood glucose by preventing reabsorption of glucose in the kidney.
  • Hypertension is common in the diabetic community. Roughly 71% of diabetic patients have blood pressure greater than 140/90 mmHg or are on hypertensive medication.
  • New evidence shows that SGLT-2 inhibitors not only help control blood glucose, but also help lower blood pressure.

Tikkanen, Ilkka, et al. “Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension.” Diabetes Care 38.3 (2015): 420-428..

Weber, Michael A., et al. “Effects of dapagliflozin on blood pressure in hypertensive diabetic patients on renin–angiotensin system blockade.” Blood pressure (2015): 1-11.

Annual Number (in Thousands) of New Cases of Diagnosed Diabetes Among Adults Aged 18-79 Years, United States, 1980-2014. CDC. www.cdc.gov