Efficacy and safety of saxagliptin in combination with insulin in Japanese patients with type 2 diabetes mellitus: a 16-week double-blind randomized controlled trial with a 36-week open-label extension

<p><b>Background</b>: We examined the efficacy and safety of saxagliptin as an add-on to insulin in Japanese patients with type 2 diabetes mellitus.</p> <p><b>Research design and methods</b>: We randomized 240 patients with type 2 diabetes mellitus on insulin monotherapy to 5-mg saxagliptin or placebo as add-on therapy for a 16-week, double-blind period. All patients received 5-mg saxagliptin and insulin for an additional 36 weeks (open-label extension). Change in hemoglobin A1c (HbA1c) at Week 16 was the main endpoint.</p> <p><b>Results</b>: At Week 16, the adjusted change in HbA1c from baseline increased by 0.51% with placebo and decreased by 0.40% with saxagliptin (difference −0.92% [95% confidence interval −1.07%, −0.76%; p < 0.001]). In patients receiving saxagliptin, reductions in HbA1c at Week 16 were maintained to Week 52, while switching from placebo to saxagliptin resulted in a similar reduction in HbA1c. The incidence of hypoglycemia was not markedly increased with saxagliptin versus placebo in the double-blind period and did not increase substantially during the open-label extension period. The efficacy and safety of saxagliptin was similar between the elderly and non-elderly patient groups.</p> <p><b>Conclusions</b>: Adding saxagliptin to ongoing insulin therapy improved glycemic control and was well tolerated in Japanese patients with type 2 diabetes.</p

Efficacy and safety of luseogliflozin added to insulin therapy in Japanese patients with type 2 diabetes: a multicenter, 52-week, clinical study with a 16-week, double-blind period and a 36-week, open-label period

<p><b>Objective:</b> To evaluate the efficacy and safety of luseogliflozin in Japanese patients with type 2 diabetes (T2D) inadequately controlled with insulin monotherapy.</p> <p><b>Methods:</b> This 52-week multicenter study entailed a 16-week, double-blind period followed by a 36-week, open-label period. Patients were randomized to receive either luseogliflozin 2.5 mg (<i>n</i> = 159) or placebo (<i>n</i> = 74) during the double-blind period. All patients who entered the open-label period received luseogliflozin. Major efficacy endpoints included the changes from baseline in HbA1c, fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and bodyweight. Safety assessments included adverse events, laboratory tests and vital signs.</p> <p><b>Results:</b> In the double-blind period, luseogliflozin significantly decreased HbA1c (−1.18%), FPG (−42.4 mg/dL), 2 hour PPG (−68.7 mg/dL) and bodyweight (−1.27 kg) compared with placebo (all <i>p</i> < .001); these reductions were maintained over 52 weeks. The changes from baseline at Week 52 were −1.00%, −35.1 mg/dL, −68.8 mg/dL and −1.81 kg, respectively (all <i>p</i> < .001). In the placebo group, favorable glycemic control and bodyweight reduction were also observed after switching to luseogliflozin. Most adverse events were mild in severity. During the double-blind period, the incidences of hypoglycemia were 20.8% and 13.5% in the luseogliflozin and placebo groups, respectively. During the 52 weeks of luseogliflozin treatment, the frequency of hypoglycemia was 33.3%, but no serious hypoglycemia occurred. The safety profile other than hypoglycemia was also acceptable. There were no new safety concerns about luseogliflozin added to insulin.</p> <p><b>Conclusion:</b> Luseogliflozin added to insulin therapy significantly improved glycemic control with bodyweight reduction and was well tolerated in Japanese patients with T2D.</p> <p><b>Clinical trial registration:</b> Japan Pharmaceutical Information Center (JapicCTI-142582).</p

Aspects of Multicomponent Integrated Care Promote Sustained Improvement in Surrogate Clinical Outcomes: A Systematic Review and Meta-analysis

OBJECTIVE The implementation of the Chronic Care Model (CCM) improves health care quality. We examined the sustained effectiveness of multicomponent integrated care in type 2 diabetes. RESEARCH DESIGN AND METHODS We searched PubMed and OvidMEDLINE (January 2000-August 2016) and identified randomized controlled trials comprising two or more quality improvement strategies from two or more domains (health system, health care providers, or patients) lasting ≥12 months with one or more clinical outcomes. Two reviewers extracted data and appraised the reporting quality. RESULTS In a meta-analysis of 181 trials (N = 135,112), random-effects modeling revealed pooledmean differences in HbA1c of20.28%(95%CI20.35 to20.21) (23.1mmol/mol [23.9 to 22.3]), in systolic blood pressure (SBP) of 22.3 mmHg (23.1 to 21.4), in diastolic blood pressure (DBP) of 21.1 mmHg (21.5 to 20.6), and in LDL cholesterol (LDL-C) of 20.14 mmol/L (20.21 to 20.07), with greater effects in patients with LDL-C ≥3.4 mmol/L (20.31 vs. 20.10 mmol/L for 12 months (SBP 23.4 vs. 21.4 mmHg, Pdifference = 0.034; DBP 21.7 vs. 20.7 mmHg, Pdifference = 0.047; LDL-C 20.21 vs. 20.07 mmol/L for 12-month studies, Pdifference = 0.049). Patients with median age <60 years had greater HbA1c reduction (20.35% vs. 20.18% for ≥60 years [23.8 vs. 22.0 mmol/mol]; Pdifference = 0.029). Team change, patient education/self-management, and improved patient-provider communication had the largest effect sizes (0.28-0.36% [3.0-3.9 mmol/mol]). CONCLUSIONS Despite the small effect size of multicomponent integrated care (in part attenuated by good background care), team-based care with better information flow may improve patient-provider communication and self-management in patients who are young, with suboptimal control, and in low-resource settings