It has been a while since Prof. Dr. Francesco Giorgino, currently vice-president of EASD and professor of endocrinology and metabolism, Head of the Division of Endocrinology at the University Hospital Policlinico Consorziale, University of Bari Aldo Moro in Italy talked with us about new trends in the management of diabetes. His words are still more than worth remembering.
The harmonization of gluco- and cardio-centric approaches in the management of diabetes has been a hot topic for some time now. New, rapidly developed therapies in the treatment of type 2 diabetes (T2D) with a weight-centric approach only recently emerged in clinical practice. Historical consideration has always been focused on glucose control as the main goal for people with diabetes and physicians in managing this disease. This practice still has a strong tradition as an approach to achieving the HbA1c target.
Professor Giorgino, what is your take on the future development of clinical approaches?
The approach mentioned above would potentially apply as a consideration to other perspectives. If you have a context in which a physician is treating obesity, it could be more of interest to use drugs to target the excess weight. It is something that is tightly linked to local practice, how physicians are trained, and to which generation of diabetologists they belong, older or younger. The younger generations of physicians are more sensitive to the issue of organ damage, the prevention of heart failure (HF), chronic kidney disease (CKD) progression, and reducing cardiovascular disease risk. This aspect is heterogeneous and based on the physician, context, setting, knowledge, level of care, etc.
What about the main goal of the treatment?
I believe that nowadays physicians should focus on each patient’s individual goal. In treating obesity, there is no goal more important than the other. We have drugs that target atherosclerotic cardiovascular disease, improve HF and CKD outcomes, they should be used especially with the higher risk patients. But not necessarily only those!
At the same time, we know that glucose control is important also for other outcomes: if a person has optimal glucose control, there are fewer risks for multiple outcomes, not only macro- and micro-vascular complications but also infections affected by the degree of glucose control. We must strive to achieve the best glucose control possible. That is my personal opinion, but I think I’m not the only one thinking that way.
Since new evidence has led to new guidelines, the society of diabetology is also talking about new diagnostic criteria and tighter glycemic targets in T2DM. Are they possible and needed?
Medicine is based on evidence, and we have evidence from intense glucose control trials that have established certain glucose targets – HbA1c targets – to pursue in people with diabetes - with some heterogeneity based on clinical features that largely derived from subgroups or a post hoc analysis of these trials. However, we must acknowledge that these trials have been conducted with drugs that do not represent the full spectrum of current therapeutic tools. Ideally, one should start those trials again with the new drugs to see, for example, whether: using drugs that do not cause hypoglycemia would lead to different outcomes or using drugs that do not cause weight gain leads to different outcomes. We have to keep in mind that UKPDS and also more recent trials such as ACCORD and ADVANCE were conducted with drugs that generally did cause weight gain and hypoglycemia. So, there has been an ongoing debate about the contribution of these adverse effects of intense glucose control as a result of those drugs.
We simply do not have the evidence to answer this question, but it seems quite logical that if you can achieve near-normal glycemia without excessive risk of hypoglycemia and weight gain or potentially even in association with weight loss, you would be better off setting HbA1c targets instead of the canonical, traditional level. Why not go below 6.5% if you can do it safely?
When dealing with T1D, should we look beyond HbA1c, and, if so, why?
When it comes to glucose control, we cannot solely focus on HbA1c. To some extent, this is potentially even true for T2D. Hb1Ac has its merits but also has its limitations. The availability of CGM information has taught us that we can improve target glucose control in these people, especially in T1D. Where glucose fluctuations are larger, and there is more glucose instability, the risk of hyperglycemia is higher and therefore CGM could provide a better picture of the level of glucose control compared to HbA1c.
Looking ahead, the challenge for people with T1D is to live their daily lives with the best glucose levels possible. This is another important condition or fact perceived by the patient in a very intense manner. People with T1D who do not achieve sufficient levels of glucose stability are very sad, stressed, and frustrated. Even for the particular purpose of improving the well-being of these patients, it is important to not only look beyond HbA1c but also to the possibility of achieving glucose levels within an appropriate range.
And by the appropriate range you mean time-in-range?
Exactly. For the particular condition I mentioned, you need to consider time-in-range, which is very well-established by recommendations of experts around the world. Glucose control is something that is even more important for people with T1D as compared to those with T2D.
Concerning keeping body weight in check, we have to acknowledge that some people with T1D do have excess weight; they are overweight or frankly obese for multiple reasons. Even though they have insulin deficiency, the large treatment doses of insulin can lead to weight gain. In this particular case, we have some interesting data on the use of SGLT-2 inhibitors in association with insulin. Insulin therapy cannot be reduced even if these agents are added to a large extent. As we know, adding SGLT2 inhibitors to insulin leads to an increased risk of ketoacidosis, something that currently has some important restrictions and limitations. But, of course, there is an unmet need to achieve not only appropriate time-in-range for glucose but also weight control, especially in certain people with T1D.
Do you consider digitalization a benefit or barrier in T1D and T2D management?
I think it is a new opportunity, but something that should be handled with care. First of all, it is important that all its new modalities of interaction are understood by the physician and explained to the patient. Not all patients are suited for this particular approach, but some will greatly benefit from it. Especially during the COVID pandemic, we were able to successfully care for patients remotely, they felt taken care of, which is very important for some of them. There were some important interventions to improve glucose control and control of other risk factors in diabetes achieved through telemedicine. In terms of T2D, I think digitalization is something that should be considered more and more, for example, some disease programs include hybrid management of patients and ensure better monitoring. However, this means that face-to-face medical visits will be less frequent than before. For T1D, pumps, and CGM, FGM devices were coupled in the meaning of digital solution platforms, collecting and providing data are shared with the physicians. It will go even further. Of course, there are also issues such as patient education, physician knowledge, interoperability of different devices, privacy, and data protection. It is not easy to address those issues, but it is an ongoing process and I’m positive that it will improve as time goes on.