使用SGLT-2抑制剂治疗2型糖尿病

大家好，欢迎收听最新一期的《Nice Talks》节目。我是主持人Liana Bravo。今天我们要讨论的是SGLT2抑制剂——一种治疗2型糖尿病的药物。这类药物除了降低血糖水平外，还具有保护心脏和肾脏的额外益处。

Hello, and welcome to the latest episode of Nice Talks. I'm your host, Liana Bravo. Today, we are talking about SGLT2 inhibitors, a medication for type two diabetes. These medicines have benefits beyond reducing blood sugar levels. They also protect the heart and kidneys.

今天与我对话的嘉宾有：查特菲尔德健康中心全科合伙人、2型糖尿病指南更新委员会主席Walker Shah医生；西布里克福德医疗中心全科医生、初级保健糖尿病学会秘书Rahul Mohan医生；以及谢菲尔德教学医院NHS基金会信托顾问医师、糖尿病专家、2型糖尿病指南更新委员会成员Sung Song医生。

I'm joined today by Doctor. Walker Shah, GP partner at Chatfield Health Centre and committee chair for the Type two Diabetes Guideline Update, as well as Doctor. Rahul Mohan, a GP at West Brickford Medical Centre and secretary of the Primary Care Diabetes Society. I'm also delighted to welcome Doctor. Sung Song, consultant physician and diabetologist at Sheffield Teaching Hospitals NHS Foundation Trust and committee member for the Type two diabetes guideline update.

感谢各位今天的参与。我想首先请教Sun医生，您能否向我们解释什么是SGLT2抑制剂，以及它们能带来哪些益处？

Thank you all for joining me today. I would like to start with you, Doctor. Sun. Could you tell us what SGLT2 inhibitors actually are and what benefits they offer?

好的。SGLT2抑制剂是一类作用机制与我们既往用药完全不同的药物。它主要通过作用于肾脏，促使葡萄糖通过尿液排出体外。这种方式不仅能改善血糖控制，还能带来一定程度的体重减轻。但更引人注目的是，过去十年间首个证明SGLT2抑制剂临床获益的研究发表时，其中显示的死亡率改善效果完全出乎我们预料。

Right. The SGLT2 inhibitors is a class of drug whereby it works quite differently from other medications that we've been using so far. In particular, it works on the kidneys and makes the kidneys excrete more glucose in the urine. By doing so it can improve the glucose control but also it can cause some weight loss. But what's more interesting is that in recent years, in the last ten years, the first study that shows the benefits of SGLT2 inhibitors was published.

随后十年间陆续发表的多项研究都一致证实了其对心肾的保护作用，某些情况下还能改善患者死亡率。获益最显著的人群包括合并心脏病、肾病、心衰的患者——无论是否患有糖尿病。

And at that time it was surprising because we didn't expect the benefit in mortality. But subsequently, various studies have been published the last ten years. And it shows a consistent benefit of cardio renal protection and also in some cases improve the mortality outcomes as well. And people that benefit most are people with heart disease and kidney disease and heart failure. Both people with diabetes and non diabetes patients.

这确实令人振奋，因为在此之前，我们用于治疗2型糖尿病的药物中极少有潜在延长寿命的效果。基于证据的高度一致性和说服力，这类药物现在被推广建议更广泛地应用于2型糖尿病患者。

So it's very exciting because up until then there's very few medications in diabetes that we use to treat type two diabetes that actually prolongs life potentially. So it was exciting. I think based on the consistency of the evidence and also the strength of the evidence, that's why this class of medications are now being promoted and recommended to be used more widely in people with type two diabetes.

2022年NICE指南建议对合并心脏病的2型糖尿病患者使用SGLT2抑制剂，并提示医生应考虑为心脏病高风险人群开具处方。但去年NICE分析50多万份健康记录发现，这类药物在英国初级诊疗中存在处方不足现象，尤其对女性、老年人和黑人群体。数据触目惊心：仅1/5合并心脏病或高风险的2型糖尿病患者获得处方，慢性心衰患者中也只有1/3使用该药物。

In 2022, NICE published guidelines recommending SGLT2 inhibitors for people with type two diabetes who also have heart conditions. The guidelines also advise doctors to consider prescribing this medication for people at high risk of developing heart disease. But last year, NICE analyzed health records of more than half a million people and discovered that these medicines are under prescribed in primary care in England, particularly to women, older people, and black people. The findings were pretty striking. Only one in five people with type two diabetes on heart disease or a high risk of developing it had a prescription, and only one in three patients with chronic heart failure had been prescribed this medication.

Shah医生，我现在想请教您，您认为是什么导致了这种低使用率？

Doctor Shah, I would like to come to you now. What do you think is driving this low uptake?

SGLT2抑制剂的使用率如此之低确实很有意思。证据表明它们通常耐受性良好，而且对患者确实有非常积极的好处，不仅在于二型糖尿病管理，还包括缺血性心脏病和肾功能障碍。当然，这三种情况在某些患者身上也可能相互关联。因此SGLT2抑制剂对这些患者具有双重甚至三重效益。

It's really interesting that there's such a low uptake of SGLT2 inhibitors. The evidence shows that they are generally well tolerated. And they do have really positive benefits for patients, not only just in type two diabetes management, but also in an ischemic heart disease and in renal dysfunction as well. And of course, the three conditions can be linked in some patients as well. So the SGLT2s have a double or triple benefit in those patients.

看到这些对患者可能非常有益的药物的使用率如此之低，确实令人遗憾。我认为这背后有多重原因。我们需要让患者更全面地了解SGLT2抑制剂的益处，而不仅仅是它们对糖尿病控制的影响。我认为这方面可能存在信息缺口，存在信息需求。

So it is very sad to see such a low uptake of these potentially very beneficial medications for these patients. And I think there's a number of reasons why that may be so. We need to better inform patients of the wider benefits of SGLT2 inhibitors, not just the impact they may have on diabetic control. And so I think maybe there's a gap there. So there's an information need, I think.

我认为如果我们能减少信息不对称，使用率可能会提高，因为患者会获得更充分的知情。另一个患者可能回避SGLT2抑制剂的原因是潜在的并发症或副作用清单。这对某些人来说可能相当可怕，这可能是他们不愿服用这种药物的原因。

And I think if we can reduce the information asymmetry, then maybe uptake will increase because patients will be better informed. Another reason why patients may shy away from SGLT2 inhibitors is the potential list of complications or side effects. And perhaps that may be quite scary for some people or some patients. And that may be a reason why they may be reluctant to take this medication.

接下来请教Mohan医生，您能否就此进一步阐述？

And coming to you Doctor Mohan, could you expand a bit more on that?

我认为确实存在多重障碍，我们可以具体分为患者相关障碍、医生相关障碍和医疗系统相关障碍。关于SGLT2抑制剂可能产生的不良反应，一直存在某些恐惧和担忧，我们持续努力解决这些问题。我们通过面对面培训模块，试图做到的是：如果他们有任何恐惧或问题，我们会予以解答并分享最佳实践。我认为医疗团队和患者尝试新疗法的意愿等因素某种程度上难以量化，这可能导致了二线抗糖尿病治疗处方上的微小差异。

I think there are definitely barriers in which we can really specify into patient related barriers, physician related barriers and the health system related barriers. And yet there has been some fears and concerns regarding the adverse effects which the SGLT2 inhibitors may have and we have constantly tried to address those fears and concerns. And our eating training modules which are face to face, this is something that we have tried to address is that if they have any fears or any questions then we are answering them and sharing our best practice. I think the factors such as willingness to try new treatments both on the part of the healthcare team as well as the patients is somewhat unmeasured. And this could have contributed to the small differences in the second line anti diabetic treatments that are being prescribed.

正如我们之前提到的，NICE研究还显示出处方方面存在显著差异，例如按年龄和性别划分。年轻患者比年长者更可能被开具SGLT2抑制剂，男性比女性更可能获得这类处方。Mohan医生，您认为是什么导致了这些差异？

As we mentioned earlier NICE's research also showed significant disparities in prescribing, for instance by age and gender. Younger patients were far more likely to be prescribed SGLT2 inhibitors than older ones, and men were more likely to receive prescriptions than women. Doctor. Mohan, what do you think could be causing these disparities?

我认为存在一些固有因素。必须理解的是，这类SGLT2抑制剂未被批准用于哺乳期或妊娠期患者，这可能成为女性处方开具的障碍。此类药物可能导致血容量不足，因此我们对老年人尤其关注体液流失或脱水问题，这可能增加跌倒风险。这也是我们非常重视的方面。

I think there are factors which are some inherent factors. And one has to understand that these SGLT2 inhibitors are not licensed to be used in patients who are breastfeeding or are pregnant. So that can prove to be a barrier for prescribing in women. This class of agent can bring about hypovolemia so we are quite sensitive about loss of volume or dehydration especially in the elderly, which might contribute to the falls. So that is also something that we are quite sensitive about.

我们还知道这种药物存在尿路感染和鹅口疮等副作用，可能导致女性使用率较低。现在，Shah医生，让我们回到您这里。Mohan医生刚才提到了一些可能导致老年人使用率较低的因素。

And we also know that this medication has side effects such as UTIs and thrush that could contribute to the lower uptake in women. Now, Doctor. Shah, let me come back to you. Doctor. Mohan was just mentioning some factors that could explain the lower uptake among older people.

还有其他原因可以解释这种差异吗？

Are there any other reasons that could explain this disparity?

我们必须记住，随着年龄增长，患者服用的药物数量往往会增加。我认为对多重用药的担忧，以及新药可能干扰现有稳定用药组合的相互作用恐惧，可能也是一个因素。因此我怀疑这是否也是原因之一。

We have to remember that as age increases, patients are more likely to be on larger number of medications than before. So I think this fear of polypharmacy and this fear of interactions of a new medication interfering with the existing stable portfolio of medications that they are consuming may be a fear as well. So I wonder whether that might be one of the factors.

NICE的分析还显示，黑人或英国黑人群体以及贫困地区人群获得处方的几率更低。Song医生，您认为这些健康不平等现象背后可能是什么原因？

The analysis conducted by NICE also revealed that Black or Black British people and those in deprived areas had lower odds of receiving a prescription. Going to you Doctor Song, what do you think could be behind these health inequalities?

我认为对于某些少数族裔群体中的社会经济弱势人群，他们与全科医生和执业护士等医疗专业人员的互动较少。我们知道当患者参与度降低或缺乏互动，导致医患接触不足时，这些患者就不太可能接受此类药物治疗。这说明当前的服务模式可能尚未优化，未能充分适应患者的利益需求。

I think for socio economic deprivation in certain ethnic groups, minority groups, engagement with the health care professionals like their GPs and practice nurses is less. We know that. So when you get the reduced engagement or lack of engagement from the patients and resulting in lack of patient contact, the patients are unlikely to be treated with these medications. I think what it tells us, the current service model is probably not optimized yet. It's not appropriate geared towards patient benefit.

因此需要审视现状，或许应该设计更创新的服务提供方式，加强对患者的教育，同时赋予他们自主权，以期更好地实现这一目标。

So that has to be looked at and perhaps devising a more innovative way of providing service, educating patients, and then empowering them as well, and hopefully improving compliance to that objective.

本月NICE更新了2型糖尿病指南，现在建议所有2型糖尿病患者（而不仅是心脏病患者）使用SGLT2抑制剂。这将提高对该疗法的认知并增加使用率。指南还呼吁开展研究以理解为何会出现这些处方差异。Shah医生，为什么让更多人获得这种药物如此重要？

This month NICE updated the type two diabetes guideline and SGLT2 inhibitors are now recommended for everyone with type two diabetes, not just those with heart disease. This will raise awareness of the treatment and increase uptake. The guideline also calls for research to understand why these prescribing disparities happen. Doctor Shah, why is it so important that more people get access to this medication?

目前我们正积极寻求如何提高SGLT2抑制剂使用率的答案。因为如果能够实现全面普及，我认为国民健康水平将显著提升。这显然主要使患者受益——他们将过上更优质、更长寿、更充实且发病率更低的生活。同时整个医疗体系也将获益，国民医疗服务体系会因相关并发症减少而降低资源消耗。

There is some momentum behind trying to get the answer to how we can increase the uptake of SGLT2 inhibitors. Because if we were to achieve perfect uptake, I think the nation would be significantly healthier than it is. And that clearly has benefits primarily for the patient because they live a better, longer, more fulfilled life and a life that has less morbidity than otherwise. But also the wider health care system benefits. The National Health Service benefits because there may be less consumption of resources as a result of complications from these conditions.

在我看来这似乎是双赢局面。对于能够耐受该药物的患者，我们确实应该努力实现这一目标。

So it seems to me like a win win situation. And for the patients who can tolerate the medication, we really should be working hard to try and achieve that goal.

在结束讨论前，我想再次请教Song医生。在服用此药物前，人们还需要考虑哪些因素？

And to wrap up a discussion, I would like to come back to you, Doctor. Song. Is there anything else that people should consider before taking this medication?

我想提出该药物使用的安全性问题。虽然我们因其在降低死亡率方面的益处而希望推广使用，但同时也需确保安全用药，以最大限度降低、避免或预防这些患者发生糖尿病酮症酸中毒的风险。

I want to raise the issue of safety of using this medication. So the flip side here is that yes, we want to promote wider usage because of the benefits it can provide in terms of mortality outcomes. But also we need to ensure it's being used safely to minimise and avoid and or prevent the risk of diabetic ketoacidosis for these patients.

开具这种药物时应采取哪些保障措施？

And what safeguards should be in place when prescribing this medicine?

某些人群确实存在DKA风险。例如采用低碳水化合物饮食者不应服用SGLT抑制剂，即将接受手术者也不应使用该药物。若出现急性病症等不适情况，应暂停用药直至完全康复，之后方可重新开始治疗。

So I mean certain groups are at risk of getting DKA. So people who are on low curry diet, for example, they should not be prescribed SGLT inhibitors. People who are going for surgery should not be prescribed this medication. Or if you become unwell, for example, with any acute illness, then they should stop taking this medication temporarily until they have recovered from the acute illness and then at that stage restart the medication when they have fully recovered.

谢谢宋医生，也感谢所有嘉宾。今天的《NICE对话》节目到此结束。感谢收听，别忘了点赞订阅。

Thank you Doctor. Song and thanks to all our guests. We have reached the end of today's episode of NICE Talks. Thank you for listening. Don't forget to like and subscribe.

获取最新动态，请关注我们的社交媒体账号NICECOMS。下次节目再见。

And for all the latest updates, follow us on social media at NICECOMS. Until next time.