New recommendations for type 2 diabetes management launched
EASD 2022 ended on a high note with the unveiling of the latest ADA/EASD consensus report on the management of hyperglycaemia in type 2 diabetes. Fifteen years since the first report, which had a narrow focus on glycaemic control, Bob Gubbay, CEO of ADA, called this ‘perhaps the best report yet’ for its broad scope and detail. The expert panel that put the report together took to the stage, in front of a packed audience, to present some key points. Dr Susan Aldridge reports.
Melanie Davies, Professor of Diabetic Medicine at the University of Leicester and co-Chair of the consensus group, introduced the main highlights of the new document. “There is a greater focus, this time, on social determinants of health, healthcare systems and equality of care, as well as an emphasis on holistic person-centred care. We also focus very much on weight goals as an essential component of comprehensive care, and we have consolidated all the evidence from recent cardiovascular outcome trials.”
Billy Collins, from the National Heart, Lung and Blood Institute at the National Institutes of Health and Peter Rossing, of the Steno Diabetes Centre, talked about the rationale, importance and context of blood glucose-lowering treatment in type 2 diabetes. “Good glycaemic control reduces microvascular complications, but the side effects of medications arise more rapidly than the benefits, so it is important to encourage the patient to keep on with them,” Billy said.
And with weight management, traditionally a goal, loss of 5 to 10% of body weight is recommended, and 10 to 15% for remission. This has long-term benefit beyond glycaemic management in terms of improved quality of life and cardiovascular risk factors. Individualised weight management goals should be set.
Finally, Peter noted the importance of putting the person with diabetes at the centre of their care and shared decision-making throughout the care cycle, from diagnosis to ongoing monitoring. Diabetes self-management education and support (DSMES) is a crucial element of this.
There has never been such a wide range of diabetes medications, including SGLT-2 inhibitors, GLP-1 receptor agonists and the new GIP/GLP-1 receptor agonist tirzepatide, and there is also new clinical trial evidence, which is covered in the new consensus report. So, choosing a therapy now goes beyond glucose lowering – there is also the impact on weight, cardiovascular and kidney health to consider.
“We want to match the ‘who’, to the ‘what’, to the ‘why’,” said Vanita Aroda of Harvard Medical School. “The full treatment algorithm reflects all three of these dimensions, where we really put the person at the centre and establish care goals with them. We now have an evidence-based toolbox to support that journey.”
Lifestyle intervention is as important as medication – and moving more is part of that. Tsvetalina Tankova of the Medical University, Sofia, stressed the importance of 24-hour physical activity for its cardiometabolic benefits. The cycle used in the new document goes – Sitting, Sweating, Stepping, Strengthening and Sleep. Tips and motivators include:
- Remember to break up sitting with movement every 30 minutes
- An increase of just 500 steps a day is associated with a 2 to 9% decrease in cardiovascular mortality
- Resistance exercise can improve insulin sensitivity
“Just a five minute brisk walk each day means a few years longer life expectancy,” she concluded.
The personalised approach
The consensus document lays new emphasis on taking personal characteristics and comorbidities into account when prescribing. Apostolos Tsapas of Aristotle University Thessaloniki said: “We believe that a choice of treatment addressing cardiorenal risk should be a component of care for people with type 2 diabetes at high risk.”
The recommendations are that in people with established atherosclerotic cardiovascular disease (ASCVD) you should use a GLP-1 receptor agonist to reduce MACE (major adverse cardiac events) or an SGLT-2 inhibitor to reduce MACE, heart failure or improve kidney outcomes. And for people without ASCVD, but with multiple risk factors, you could use the above, but bear in mind that the evidence for their benefit in such cases is weaker, being based upon subgroup analysis. Also, there is no difference in MACE with GLP-1 receptor agonists and SGLT-2 inhibitors with baseline HbA1c or use of metformin. And if they are still above their glycaemic target, you can go for combination therapy, adding a medication from the other category. All this should be factored into the shared decision-making process
Jennifer Green of Duke University School of Medicine discussed the consensus recommendations for those with chronic kidney disease (CKD). “Assuming they are already on the maximum tolerated dose of an ACE inhibitor/ARB, use an SGLT-2 inhibitor with evidence of reducing CKD progression, and this is no longer dependent on the degree of albuminuria. Or use a GLP-1 receptor agonist instead, if the SGLT-2 inhibitor isn’t tolerated.” This reduces the person’s risk of MACE and improves heart failure and kidney outcomes, regardless of estimated glomerular filtration rate (eGFR).
“It’s also very important that we take the age of the person with diabetes into consideration,” she continued “Older people with type 2 get less benefit from intensive glycaemic control. Those over 70 and under 40 are under-represented in trials, so informed decisions on treatment are therefore limited by lack of age-specific data.”
This is changing, however. For instance, a recent analysis showed that people aged 65 or over enjoyed the same cardiovascular and kidney outcomes as younger people in trials. However, there weren’t enough participants over the age of 75 to reach a conclusion for this group.
So, the recommendation is that the selection of medications should not depend on age. However, if the person is frail or multimorbid, this selection might need modification for safety and tolerability and unnecessary medications should be de-prescribed to avoid hypotension and hypoglycaemia.
“On the flip side, many young people are now developing type 2 diabetes. They have a very high risk of complications and should be treated accordingly,” said Vanita. Young people have more rapid deterioration in their glycaemic control and respond less well to medication. Therefore, early use of combination therapy to manage hyperglycaemia in this group may be considered – as the VERIFY trial shows, this [vildagliptin plus metformin] is better than metformin alone.”
Finally, although evidence on outcomes by ethnicity or gender is limited, because of under-representation in trials, there is no reason to restrict prescribing on these grounds.
Chantal Mathieu, of KU Leuven and also President Elect of EASD, kicked off discussion about how the recommendations can be put into practice.
“Remember, the person at the centre of this all should be the person with diabetes,” she said. “Some things may have changed in our algorithm for management but what has not changed is avoiding clinical inertia – so re-assess every three to six months.”
On the need for integrated care, Sylvia Rosas from the Joslin Diabetes Center said “We have to acknowledge the lifelong and evolving nature of diabetes. Know your local resources, individualise care, monitor and address inequality and social determinants and don’t forget to incorporate comorbidities. Finally, do embrace DSMES [diabetes self0management education and support] – it is as important as medications.”
Then Nisa Marathur of Johns Hopkins University shared some practical tips on choosing a glucose-lowering medication (in addition to those laid out above) “We need to continually update our knowledge of glucose pharmacotherapy and prioritise organ-protective medications in those at high risk.” There is still a place for insulin in type 2 diabetes, she continued, but use a GLP-1 receptor agonist prior to insulin. Start with a basal insulin, intensify it in a timely fashion, continuing the other medications, and refer the patient to DSMES when initiating, or advancing to basal bolus.
“We’re very fortunate in how much diabetes management has changed over the last 20 years, but most of these innovations are not getting to people with diabetes.” To improve the situation, three things are needed. First, we need to consider delivery arrangements in local settings. Then, attention should be paid to governance and accountability. Finally, implementation should occur at three levels – the healthcare system, the healthcare setting and the healthcare workers themselves.
Knowledge gaps, call to action
John Buse, of the University of North Carolina School of Medicine and co-Chair of the consensus group, pointed out that insulin was rapidly developed after its discovery over 100 years ago, while COVID-19 has given rise to extraordinarily accelerated treatments and vaccines. Couldn’t the same proactive approach now be used to further new treatments for type 2 diabetes?
“Major opportunities to improve diabetes outcomes in the near term come from more effective implementation of best evidence through organisation of care at all levels – national to individual – and from addressing the social determinants of health. Everyone has a role to play in better implementation with a focus on equity,” he said.
The key opportunities to be seized moving forward include more basic science to be applied to next generation interventions. Then there are precision medicine initiatives to optimally target interventions, based upon the wide heterogeneity of people with diabetes.
On the other hand, there are significant knowledge gaps that need to be filled. For instance, more attention should be paid to subgroups in clinical trials – including youth, the frail, elderly and gender. “These are just minimal steps towards health justice,” John said. And there is also a need for more comparative effectiveness studies in weight management to see if a reasonable treatment algorithm can be constructed. The same is true of cardiorenal protection – let’s have more information on comparative effectiveness, combination therapy and cost-effectiveness in moderate to low-risk populations.
And although there is emerging evidence on comorbidities like non-alcoholic fatty liver disease (NAFLD), advanced CKD and cognitive impairment, none of these populations has yet been adequately studied. Finally, it should be noted that what we know about screening and prevention of type 2 diabetes is based upon studies that are over two decades old. “The population at risk today is very different. We need to know that current recommendations are actually based upon today’s population,” John said.
The panel shared their own personal main messages from the document they had worked so hard to put together. Billy Collins said: “I would recommend strict adherence to the social determinants of health. This is something that has plagued modern medicine for quite some time and it’s refreshing to hear and see the social determinants of health actually manifesting in clinical medicine. So, I think moving forward we’ll be in a better place, to move forward on the social determinants of health and I think we can be proud of ourselves to improve patient outcomes as a result.”
Chantal Mathieu added. “I want to take up [the point about] how we can globalise these recommendations. When we shouted out ‘make it work’ earlier, we really meant it. There’s no excuse not to make it work. You’re all intelligent people, with teams around you. We do acknowledge your economic realities, but there’s always something you can do. Take the lifestyle advice, take into account social determinants of health, use the agents you have in your hands. Do not be inert and, especially, put the person with diabetes at the centre and make him or her part of the team. That is the essence, and there’s no excuse not to make it work.”
On dissemination of the consensus document, Melanie Davies noted that the slides and papers would go out to local providers and their teams. They would be particularly useful to people starting out their careers in diabetes care and to patient groups. “If we can disseminate this as much as possible and really get things into practice, I think it will make a real difference to people with diabetes,” she concluded.
To read the consensus document, go to: Davies M, Aroda V, Collins B, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mahieu C, Mingrone G, Rossing P, Tankova T, Tsapas A, Buse J. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 24 September 2022.
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Any opinions expressed in this article are the responsibility of the EASD e-Larning Programme Director, Dr Eleanor D Kennedy.