SGLT2 inhibitors for the treatment of diabetes: a patent review (2013-2018)

Introduction: The sodium-glucose co-transporter 2 (SGLT2) is ascribed to target renal tubular glucose re-absorption, and its inhibition has been proved to induce glucosuria which improves the glycemic index. Accordingly, SGLT2 inhibitors have found to be the promising class of antidiabetic agents for the management of type 2 diabetes mellitus. A large number of SGLT2 inhibitors have developed through structural modification and investigated for their ability to selectivity inhibit SGLT2 transporters with better bioavailability.

Areas covered: This review comprises a summary of patent applications (2013–2018) of SGLT2 inhibitors with focus on chemical structural advancement and therapeutic potentials in the management of diabetes and related disorders.

Expert opinion: SGLT2 inhibitors exert multiple metabolic benefits, including reduced glycated hemoglobin (HbA1c), improved glycemic control (fasting and postprandial), reduced body weight, reduced systolic and diastolic blood pressure and improved HDL cholesterol. Due to the virtue of no interference with insulin action and secretion, their efficacy remains the same even in presence of progressive β cell failure in type 2 diabetes. Additionally, few members of this class have been reported to exhibit cardioprotective, renoprotective, and anticancer activity. However, more study on the long-term outcomes in patients taking SGLT2 inhibitors is warranted.     

Economic Evaluation of Factorial Trials: Cost-Utility Analysis of the Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes 2 × 2 × 2 Factorial Trial of Atorvastatin,Omega-3 Fish Oil,and Action Planning

ObjectivesWe applied principles for conducting economic evaluations of factorial trials to a trial-based economic evaluation of a cluster-randomized 2 × 2 × 2 factorial trial. We assessed the cost-effectiveness of atorvastatin, omega-3 fish oil, and an action-planning leaflet, alone and in combination, from a UK National Health Service perspective.MethodsThe Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes (AFORRD) Trial randomized 800 patients with type 2 diabetes to atorvastatin, omega-3, or their respective placebos and randomized general practices to receive a leaflet-based action-planning intervention designed to improve compliance or standard care. The trial was conducted at 59 UK general practices. Sixteen-week outcomes for each trial participant were extrapolated for 70 years using the United Kingdom Prospective Diabetes Study Outcomes Model v2.01. We analyzed the trial as a 2 × 2 factorial trial (ignoring interactions between action-planning leaflet and medication), as a 2 × 2 × 2 factorial trial (considering all interactions), and ignoring all interactions.ResultsWe observed several qualitative interactions for costs and quality-adjusted life-years (QALYs) that changed treatment rankings. However, different approaches to analyzing the factorial design did not change the conclusions. There was a ≥99% chance that atorvastatin is cost-effective and omega-3 is not, at a £20 000/QALY threshold.ConclusionsAtorvastatin monotherapy was the most cost-effective combination of the 3 trial interventions at a £20 000/QALY threshold. Omega-3 fish oil was not cost-effective, while there was insufficient evidence to draw firm conclusions about action planning. Recently-developed methods for analyzing factorial trials and combining parameter and sampling uncertainty were extended to estimate cost-effectiveness acceptability curves within a 2x2x2 factorial design with model-based extrapolation.     

绝经后女性2型糖尿病伴骨质疏松患者骨密度与骨代谢指标的相关性分析

目的分析研究绝经后女性2型糖尿病伴骨质疏松症患者骨密度与骨代谢指标的相关性。方法选取2013年10月至2017年05月于重庆医科大学附属第一医院内分泌内科住院的绝经后女性2型糖尿病患者385名。搜集其基本资料、骨代谢指标及骨密度等。根据T值将这些患者分为骨质疏松组(233例)、骨量减少组(101例)和骨量正常组(51例),比较三组间骨代谢指标的变化,并对骨密度(bone mineral density,BMD)与各项骨代谢指标进行相关性分析。结果 1型前胶原氨基末端前肽(Type I procollagen N-terminal propeptide,P1NP)、骨钙素(bone Gla protein,BGP)在骨质疏松组显著高于骨量减少组、骨量正常组(P0.05);随着骨密度的降低,1型胶原羧基端肽β特殊序列(β-Carboxyl terminal peptide,β-CTX)逐渐升高,骨质疏松组、骨量减少组与骨量正常组相比较差异有统计学意义(P0.05);Spearman等级相关分析示P1NP、BGP、β-CTX与骨密度呈负相关,25(OH)D_3与骨密度呈现正相关。结论绝经后女性2型糖尿病伴骨质疏松症患者骨密度与骨代谢指标有一定的相关性,有助于预测骨折风险并及时抗骨质疏松治疗。     

Faut-il être adventiste du 7 Jour pour être en bonne santé ?

Many health-related research studies among Seventh-day Adventists (SDA) were published since 1958. Californian and Norwegian studies have shown that SDA have lower coronary mortality rates than the general population. This finding is usually attributed to the lifestyle advocated by the Seventh-day Adventist church with greater physical activity, lower median BMI, abstention from use of alcohol and tobacco, food habits characterized by a large intake of fruits, vegetables, cereal fiber, unsaturated fatty acids and a low consumption of saturated fats. The results about cancer incidence were discussed. Californian studies have shown significantly decreased relative risk in SDA than in the general population. Japanese studies have also reported lower risk of cancers in men with lifestyles similar to those of SDA. By contrast the Norwegian study of SDA has shown that the risk of cancer seems to be similar to that of the general population. Some studies reported a greater prevalence of type 2 diabetes in the non vegetarian SDA than the vegetarian. Compared with vegetarian, non vegetarian SDA reported more medication use, more chronic diseases, more hospitalizations and surgeries. Lifestyle choices of SDA as above described could prevent a great many coronary artery disease and type 2 diabetes. This lifestyle is now emphasized by French PNNS.     

精液中PAI-1含量与精液液化的关系

目的测定精液中纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor type-1,PAI-1)的含量,探讨精液的液化机制。方法分别检测门诊患者1h内不液化精液40例(A组)和1h内液化精液30例(B组)中PAI- 1的含量。结果A组PAI-1含量为(10．25±0．75)ng/ml,B组为(6．46±0．37)ng/ml,A组含量显著高于B组,P＜0．01,差异有统计学意义。精液中PAI-1含量与精液液化时间的相关性r=0．362,P＜0．01,呈正相关。结论精液中PAI-1含量升高,可导致精液液化时间延长,可作为检测精液粘稠度的一个相对指标。     

2型糖尿病患者绝经期骨密度与甲状旁腺素、雌激素相关性研究

目的 观察2型糖尿病妇女绝经期骨密度与甲状旁腺素、雌激素相关性研究.方法 测定绝经期2型糖尿病妇女伴骨质疏松（A）组及绝经期2型糖尿病妇女无骨质疏松（B）组的左侧髋部股骨颈、大转子、华氏三角区、及腰椎L2～L4正侧位的骨密度和血清中骨代谢指标,如：骨钙素、碱性磷酸酶、钙、磷、甲状旁腺素、雌二醇、Ⅰ型胶原羧基末端终肽（β-CTx）的浓度,对骨密度与多个变量之间的关系进行相关分析,并对（A）组血清中的甲状旁腺素、雌二醇、骨钙素、β-CTx与不同部位的骨密度之间的关系进行多元逐步回归分析.结果绝经期2型糖尿病妇女（B）组的腰椎、大转子、华氏三角区、股骨颈等骨密度指标明显低于对照组（A）（P＜0.05）;2型糖尿病绝经期妇女血清中雌二醇水平与腰椎L2～L4骨密度呈正相关（P＜0.032）;甲状旁腺素水平与股骨颈骨密度呈负相关（P＜0.034）.结论 绝经期2型糖尿病患者甲状旁腺素和雌激素水平与骨密度密切相关,分别可以用于预测骨质疏松发生的不同部位.