Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension

Tikkanen I, Narko K, Zeller C, et al; for the EMPA-REG BP Investigators. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care. 2014;Epub ahead of print. DOI: 10.2337/dc14-1096.


Hypertension affects approximately two-thirds of patients with diabetes and is a significant contributing factor to cardiovascular complications. Empagliflozin is a sodium glucose co-transporter2 (SGLT2) inhibitor that leads to increased urinary glucose excretion via an insulin-independent mechanism of action. 
 
EMPA-REG BP assessed the efficacy, safety, and tolerability of empagliflozin 10 mg and 25 mg qd on blood pressure and glycemic control among subjects with type 2 diabetes (A1C ≥7.0 to ≤10.0%) and hypertension (mean seated office SBP 130-159 mm Hg and DBP 80-99 mm Hg). Patient demographics and baseline characteristics were balanced across treatment groups. The majority of subjects were male (60%), white (94%), older (60 yrs), and obese (mean BMI 32.6 kg/m2). Most were diagnosed with type 2 diabetes>5 years ago (71.7%) and were receiving ≥1 antihypertensive medications (92.5%). The primary endpoints were A1C change and mean 24-hr SBP change at Week 12. Secondary endpoints included mean 24-hour DBP change and body weight change at Week 12.
 Reductions from baseline in mean 24-hour SBP and DBP were significantly greater with empagliflozin 10 and 25 mg compared with placebo at Week 12:
  • The difference in 24-hr SBP between empagliflozin 10 mg and placebo was -3.44 (95% CI -4.68 to -2.09; P<0.001)
  • The difference in 24-hr DBP between empagliflozin 10 mg and placebo was -1.36 (95% CI -2.15 to -0.56; P<0.001)
  • The difference in 24-hr SBP between empagliflozin 25 mg and placebo was -4.16 (95% CI -5.50 to -2.83; P<0.001)
  • The difference in 24-hr DBP between empagliflozin 25 mg and placebo was -1.72 (95% CI -2.51 to -0.93; P<0.001)
Subjects with 24-hr mean ABPM ≥130/80 mm Hg at baseline had greater decreases in mean 24-hr SBP and DBP compared with placebo at Week 12 than those with BP <130/80 mm Hg at baseline. This suggests that the risk of hypotension in normotensive patients may be low. Reductions from baseline in mean seated office SBP and DBP were significantly greater with empagliflozin10 and 25 mg compared with placebo at Week 12, consistent with ABPM results.


 A1C reductions from baseline were significantly greater with empagliflozin compared with placebo at Week 12:
  • The difference in A1C between empagliflozin 10 mg and placebo was -0.62% (95% CI -0.72 to -0.52; P<0.001)
  • The difference in A1C between empagliflozin 25 mg and placebo was -0.65% (95% CI -0.75 to -0.55; P<0.001)
  Reductions in body weight were also significantly greater with empagliflozin compared with placebo at Week 12:
  •  
  • The difference in body weight between empagliflozin 10 mg and placebo was -1.49 kg (95% CI -1.85 to -1.13; P<0.001)
  • The difference in body weight between empagliflozin 25 mg and placebo was -1.98 kg (95% CI -2.33 to -1.62; P<0.001) 

Most subjects (97%) with one or more adverse events (AEs) reported only events that were mild or moderate in intensity. Serious AEs were reported in a higher proportion of patients receiving placebo than empagliflozin. One was considered drug-related by the investigator (sudden death in a patient receiving empagliflozin 10 mg). The most frequently reported drug-related AEs were frequent urination, hypoglycemia, polyuria, and thirst. Events consistent with volume depletion were reported by two patients: one receiving placebo (hypotension and orthostatic hypotension) and one receiving empagliflozin 10 mg (syncope), and was not considered drug related. The number of patients with a positive orthostatic BP test increased in all groups, with a higher proportion of patients in the empagliflozin groups than the placebo group at Week 12.

Confirmed hypoglycemic AEs were reported in more patients receiving empagliflozin than placebo, none of which required assistance or was severe. The percentage of patients with events consistent with genital infection was higher with empagliflozin than placebo. Events consistent with genital infection were of mild or moderate intensity in all cases and led to premature discontinuation in two patients (both receiving empagliflozin 25 mg). Small decreases in eGFR were seen in the 25 mg empagliflozin group, which returned to baseline at follow-up. There were small increases from baseline in total cholesterol and LDL cholesterol with empagliflozin 25 mg compared with placebo.

 Summary:
  • In EMPA-REG BP, treatment with the SGLT2 inhibitor, empagliflozin, for 12 weeks led to significant and clinically meaningful improvements in 24-hr systolic blood pressure and diastolic blood pressure compared with placebo
  • Significant reductions in A1C and body weight were also seen with emagliflozin vs placebo
  • The safety and tolerability profile for empagliflozin was consistent with other SGLT2 inhibitors
  • The mechanism by which empagliflozin reduces BP has yet to be fully elucidated, but may be related to improved glucose control, weight loss, volume contraction due to osmotic diuresis, and improved arterial stiffness
  • Reductions in SBP and DBP have also been observed with other SGLT2 inhibitors

All slides available for download in the Slide Library.

Empagliflozin is not FDA-approved in the United States for the treatment of hypertension or overweight/obesity.

ABPM=ambulatory blood pressure monitoring; DBP=diastolic blood pressure; SBP=systolic blood pressure 

Related content: 

For more on SGLT2 inhibitors, click here. 

  

Any pharmacologic agents discussed are approved for use in the United States by the U.S. Food and Drug Administration (FDA) unless otherwise noted. Consult individual prescribing information for approved uses outside of the United States. 

November 2014 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

Previous Article
Weight-loss therapy in type 2 diabetes effects of phentermine and topiramate extended-release  

Back to
Recent Diabetes Articles  

BG Footer

 

 

Last Modified: 12/10/2014