Urinary Protein as a Marker for Systolic Blood Pressure Reduction in Patients with Type 2 Diabetes Mellitus Participating in an In-Hospital Diabetes Education Program

2011 ◽  
Vol 39 (4) ◽  
pp. 70-75
Author(s):  
Kenta Okada ◽  
Michiaki Miyamoto ◽  
Kazuhiko Kotani ◽  
Hiroaki Yagyu ◽  
Jun-ichi Osuga ◽  
...  
Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Michael A Weber ◽  
James List ◽  
Traci A Mansfield ◽  
Shamik J Parikh ◽  
Agata Ptaszynska

Background: Hypertension is a common comorbidity in patients with type 2 diabetes mellitus (T2DM). Initial treatment is usually with an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB), with other antihypertensive therapies (AHTs) added if needed. Dapagliflozin (DAPA) increases urinary glucose excretion accompanied by diuresis and weight loss, which contributes to blood pressure (BP) reduction. Here we evaluate the proportions of patients achieving combined HbA1c and systolic blood pressure (SBP) reduction with DAPA in two studies of patients with both inadequately controlled T2DM and hypertension. Methods: Patients with both inadequately controlled T2DM (HbA1c 7.0-10.5%) and hypertension (seated SBP / diastolic BP: 140-164 / 85-104 mmHg) despite receiving glucose-lowering drugs and an ACEi or ARB (Study 1) plus a 2nd AHT agent (Study 2) were randomized to receive double-blind DAPA 10 mg or placebo for 12 weeks. Primary results have been presented previously; here we present proportions of patients achieving combined changes from baseline (Δ) in HbA1c and SBP. Results: In Study 2, additional AHT drugs were thiazide/thiazide-like diuretics (~44%), calcium channel blockers (~27%), and beta blockers (~27%). Across both studies, 520 and 522 patients had available paired ΔHbA1c and ΔSBP values in the DAPA and placebo groups, respectively. More patients achieved combined ΔHbA1c and ΔSBP reduction with DAPA (n=325; 62.5%) vs placebo (n=190; 36.4%) (Figure - dotted boxes). Considering more stringent thresholds, more patients achieved combined reductions in ΔHbA1c of ≥0.5% and ΔSBP of ≥5 mmHg with DAPA (n=194; 37.3%) vs placebo (n=86; 16.5%) (Figure - solid boxes). Conclusions: In T2DM patients with hypertension on glucose-lowering therapies and an ACEi or ARB ± 1 additional AHT, adding dapagliflozin achieved clinically significant combined HbA1c and SBP reductions over 12 weeks in greater numbers of patients than placebo.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Pablo Lapuerta ◽  
Paul Strumph ◽  
Philip Banks ◽  
Ikenna Ogbaa ◽  
Brian Zambrowicz ◽  
...  

Introduction: Selective sodium-glucose cotransporter 2 (SGLT2) inhibitors target only the kidney, and they have reduced efficacy when patients with type 2 diabetes mellitus (T2DM) have renal impairment (RI). LX4211 blocks sodium and glucose absorption in the gastrointestinal tract by inhibition of SGLT1, and it enhances urinary sodium and glucose excretion in the urine through inhibition of SGLT2. The dual SGLT1/2 action of LX4211 was anticipated to reduce systolic blood pressure (SBP) in addition to improving glucose control in the setting of RI. Methods: This analysis explored the effect of LX4211 on SBP in a clinical trial of patients with T2DM and moderate to severe RI. Patients (N=31) were randomly assigned to be treated with LX4211 (400 mg, N=16) or placebo (N=15) qd for 7 consecutive days. Postprandial glucose levels after a standard high glucose meal served as the primary measure of pharmacodynamic activity. Baseline and Day 8 trough SBP measures were each an average of 3 seated assessments. Results: Mean baseline characteristics included age 66.4 years, estimated glomerular filtration rate (eGFR) 43.4 mL/min/1.73 m 2 , and SBP 130.9 mmHg. Postprandial glucose area under the curve (sampled from pre-dose to 4 hours post meal) was reduced from Baseline to Day 7 by 169.3 mg*hr/dL on LX4211 compared to placebo (p=0.003). Day 8 SBP reductions were 11.4 mmHg on LX4211 and 0.0 mmHg on placebo (p=0.045 for difference between groups). Patients with greater RI (eGFR <45 mL/min/1.73 m2) treated with LX4211 (N=6) had a 10.5 mmHg SBP reduction compared to 0.3 mmHg on placebo (N=9). The difference between seated and standing SBP did not change with LX4211 (0.0 mmHg change, Day 8 vs. Baseline). There were no reports of hypotension, hypovolemia, no serious adverse events, and no patient discontinued due to an adverse event. Mild hypoglycemia was reported in 1 LX4211 patient compared to 2 placebo patients. Conclusions: LX4211 may reduce SBP and enhance glycemic control in T2DM patients with moderate to severe RI.


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