Efficacy and safety of luseogliflozin in Caucasian patients with type 2 diabetes: results from a phase III, randomized, placebo-controlled, clinical trial.

INTRODUCTION: Most data demonstrating the efficacy and safety of luseogliflozin (luseo) in people with type 2 diabetes mellitus (T2DM) originate from the Japanese population. This study evaluated luseo versus placebo (PCB) as add-on to metformin in a Caucasian population with inadequately controlled T2DM. RESEARCH DESIGN AND METHODS: This was a multicenter, randomized, double-blind, PCB-controlled, parallel-group study. Patients aged 18-75 years with inadequately controlled T2DM (glycated hemoglobin (HbA1c) ≥7% to ≤10% (≥53 to ≤86 mmol/mol)) despite a diet and exercise program and on a stable metformin regimen were eligible. Patients were randomized to one of three luseo groups (2.5, 5.0 and 10.0 mg) or PCB for 12 weeks (W12). The primary endpoint was change in HbA1c expressed as least-square means from baseline (W0) to W12. RESULTS: A total of 328 patients were randomized: PCB (n=83) and luseo 2.5 mg (n=80), 5.0 mg (n=86), and 10.0 mg (n=79). Mean age (±SD) was 58.5±8.8 years; 64.6% were women; body mass index was 31.5±3.4 kg/m2; and HbA1c was 8.54±0.70. At W12, mean reductions in HbA1c from W0 were -0.98%, -1.09%, -1.18%, and -0.73% in the luseo 2.5, 5.0 and 10.0 mg, and PCB groups, respectively, all of which were statistically significant. Compared with PCB, HbA1c levels were significantly decreased by 0.25% (p=0.045), 0.36% (p=0.006), and 0.45% (p=0.001) in the luseo 2.5, 5.0, and 10.0 mg groups, respectively. In all luseo dose groups, reductions in body weight were statistically significant compared with PCB. Data from the safety analysis were consistent with the known luseo safety profile. CONCLUSIONS: All doses of luseo as add-on to metformin in Caucasian patients with uncontrolled T2DM demonstrated significant efficacy in decreasing HbA1c after W12 of treatment. TRIAL REGISTRATION NUMBER: ISRCTN39549850.

Effectiveness and Tolerability of Bisoprolol/Perindopril Single-Pill Combination in Patients with Arterial Hypertension and a History of Myocardial Infarction: The PRIDE Observational Study.

INTRODUCTION: This study assessed the real-life effectiveness of a single-pill combination (SPC) of bisoprolol/perindopril for controlling blood pressure (BP) and symptoms of angina in patients with hypertension and a history of myocardial infarction (MI). METHODS: Eligible patients with arterial hypertension and a history of MI were aged 18-79 years and had initiated bisoprolol/perindopril SPC within 3 months of study enrollment as part of routine Russian clinical practice. The primary endpoint was mean change in systolic and diastolic BP (SBP/DBP) at week 12 compared with baseline (data collected retrospectively). Secondary endpoints were assessed at weeks 4 and 12 and included mean change in resting heart rate (HR), proportion of patients reaching target level of resting HR, antianginal effectiveness of the SPC, and proportion of patients reaching target BP levels. RESULTS: A total of 504 patients were enrolled, of whom 481 comprised the full analysis set (mean age 61.4 ± 8.9 years, 68% men). Mean baseline SBP/DBP and HR values were 148.9 ± 16.8/87.7 ± 11.0 mmHg and 77.4 ± 10.5 bpm, respectively. Mean durations of hypertension and CAD were 12.8 ± 8.4 and 6.1 ± 6.3 years, respectively, and time since MI was 3.8 ± 5.3 years. At week 12, SBP/DBP had decreased by 24.9/12.2 mmHg (P < 0.001 vs baseline). Target BP (< 140/90 mmHg) was achieved by 69.8% and 95.9% of patients at weeks 4 and 12, respectively, and target HR (55-60 bpm) by 17.3% and 34.5% at weeks 4 and 12 versus 3.1% at baseline (P < 0.001). Reductions in angina attacks, nitrate consumption, and improvements in HR were statistically significant. Treatment was well tolerated. CONCLUSION: Treatment of symptomatic patients with CAD, hypertension, and a history of MI with a bisoprolol/perindopril SPC was associated with significant decreases in SBP/DBP and a high proportion of patients achieving BP treatment goals. This was accompanied by improvements in angina symptoms and reductions in HR in a broad patient population representative of those seen in everyday clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04656847.