Chan Juliana C N, Yang Aimin, Chu Natural, Chow Elaine
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.
Diabetes Obes Metab. 2024 Aug;26 Suppl 3:55-74. doi: 10.1111/dom.15700. Epub 2024 Jul 11.
Evidence-based guidelines provide the premise for the delivery of quality care to preserve health and prevent disabilities and premature death. The systematic gathering of observational, mechanistic and experimental data contributes to the hierarchy of evidence used to guide clinical practice. In the field of diabetes, metformin was discovered more than 100 years ago, and with 60 years of clinical use, it has stood the test of time regarding its value in the prevention and management of type 2 diabetes. Although some guidelines have challenged the role of metformin as the first-line glucose-lowering drug, it is important to point out that the cardiovascular-renal protective effects of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists were gathered from patients with type 2 diabetes, the majority of whom were treated with metformin. Most national, regional and international guidelines recommend metformin as a foundation therapy with emphasis on avoidance of therapeutic inertia and early attainment of multiple treatment goals. Moreover, real-world evidence has confirmed the glucose-lowering and cardiovascular-renal benefits of metformin accompanied by an extremely low risk of lactic acidosis. In patients with type 2 diabetes and advanced chronic kidney disease (estimated glomerular filtration rate 15-30 mL/min/1.73m), metformin discontinuation was associated with an increased risk of cardiovascular-renal events compared with metformin persistence. Meanwhile, it is understood that microbiota, nutrients and metformin can interact through the gut-brain-kidney axis to modulate homeostasis of bioactive molecules, systemic inflammation and energy metabolism. While these biological changes contribute to the multisystem effects of metformin, they may also explain the gastrointestinal side effects and vitamin B12 deficiency associated with metformin intolerance. By understanding the interactions between metformin, foods and microbiota, healthcare professionals are in a better position to optimize the use of metformin and mitigate potential side effects. The United Kingdom Prospective Diabetes Study and the Da Qing Diabetes Prevention Program commenced 40 years ago provided the first evidence that type 2 diabetes is preventable and treatable. To drive real-world impact from this evidence, payors, practitioners and planners need to co-design and implement an integrated, data-driven, metformin-based programme to detect people with undiagnosed diabetes and prediabetes (intermediate hyperglycaemia), notably impaired glucose tolerance, for early intervention. The systematic data collection will create real-world evidence to bring out the best of metformin and make healthcare sustainable, affordable and accessible.
循证指南为提供优质护理以维护健康、预防残疾和过早死亡提供了前提。系统收集观察性、机制性和实验性数据有助于构建用于指导临床实践的证据等级体系。在糖尿病领域，二甲双胍于100多年前被发现，经过60年的临床应用，其在2型糖尿病预防和管理中的价值经受住了时间的考验。尽管一些指南对二甲双胍作为一线降糖药物的作用提出了质疑，但需要指出的是，钠-葡萄糖协同转运蛋白2抑制剂和胰高血糖素样肽1受体激动剂的心血管-肾脏保护作用是从2型糖尿病患者中收集到的，其中大多数患者都接受过二甲双胍治疗。大多数国家、地区和国际指南都推荐二甲双胍作为基础治疗药物，强调避免治疗惰性并尽早实现多个治疗目标。此外，真实世界证据证实了二甲双胍的降糖作用以及心血管-肾脏益处，同时乳酸酸中毒风险极低。在2型糖尿病和晚期慢性肾脏病（估计肾小球滤过率为15 - 30 mL/min/1.73m²）患者中，与持续使用二甲双胍相比，停用二甲双胍与心血管-肾脏事件风险增加相关。与此同时，可以理解的是，微生物群、营养素和二甲双胍可通过肠-脑-肾轴相互作用，调节生物活性分子的稳态、全身炎症和能量代谢。虽然这些生物学变化促成了二甲双胍的多系统效应，但它们也可能解释了与二甲双胍不耐受相关的胃肠道副作用和维生素B12缺乏。通过了解二甲双胍、食物和微生物群之间的相互作用，医护人员能够更好地优化二甲双胍的使用并减轻潜在副作用。40年前启动的英国前瞻性糖尿病研究和大庆糖尿病预防研究首次提供了2型糖尿病可预防和可治疗的证据。为了推动这一证据在现实世界产生影响，支付方、从业者和规划者需要共同设计并实施一个综合的、以数据为驱动的、基于二甲双胍的项目，以检测未确诊的糖尿病和糖尿病前期（中间高血糖）患者，尤其是糖耐量受损患者，以便进行早期干预。系统的数据收集将创造真实世界证据，充分发挥二甲双胍的优势，使医疗保健可持续、可负担且可及。
