People I see with type 2 diabetes will often tell me that they just wish that they could treat their diabetes and have it go away. Certainly, we as health care providers would love nothing more than to fulfill this desire.
While we have long been focused on diabetes control, should remission of type 2 diabetes be the goal?
First, some terminology: Several terms have been used over the years to describe type 2 diabetes ‘going away’, including ‘remission’, ‘reversal’, ‘resolution’, and ‘elimination’. It is now well accepted that ‘remission’ is the correct term, because ‘remission’ quite correctly implies that the type 2 diabetes can come back (as it often does – more on this below).
Secondly: There has been a lot of confusion around what the definition of diabetes remission should be. A group convened by the American Diabetes Association published a consensus report defining remission of type 2 diabetes as having an A1C <6.5% for at least 3 months after stopping glucose-lowering medication, at least 3 months after bariatric surgery and stopping glucose lowering medication, or at least 6 months after starting a lifestyle approach.
Some studies have shown that lifestyle changes can put type 2 diabetes into remission. For example, the DiRECT trial demonstrated that amongst people who were earlier in their diabetes journey (less than 6 years’ duration) and able to lose and maintain 10kg (22lb) weight loss for 2 years with a lifestyle intervention, 64% achieved remission of their diabetes. While this is encouraging, the reality is that lifestyle changes to lose and maintain weight loss are very difficult to sustain long term. The data show us again and again that the vast majority of people who lose weight successfully, regain the weight. This is due to our natural biology, which defends body weight (as blogged previously). So as much as I love the idea of ‘doing it naturally’, the reality is it rarely works long term. That being said, some people very early on in their type 2 diabetes may have a very powerful response to lifestyle, or even just one medication – sometimes we see several percent A1C drop with these steps. As blogged previously, people who enjoy this very impressive A1C response are demonstrating some reversibility of their insulin-producing beta cell dysfunction. For these people, perhaps remission of their diabetes is an appropriate goal. But for many people, with a longer history of diabetes (and thus a more tired pancreas (nonreversible beta cell dysfunction)), and those for whom weight management proves more challenging to achieve and maintain (ie most people), setting remission as a goal would not be appropriate.
Another extremely important point is that there are two classes of diabetes medications that have additional, powerful benefits beyond improvement in blood sugars: namely, the GLP1 receptor agonists (GLP1RAs), and the SGLT2 inhibitors (SGLT2i’s). While I am all for my patients needing less medications if possible, it may not be appropriate to stop these treatments if they are providing additional health benefits (remember that diabetes remission requires, by definition, that medications are stopped).
The GLP1RAs are the class of diabetes medications that provide the most weight loss, and two of them are approved (at higher doses) for weight loss in people who have never even had diabetes (liraglutide and semaglutide). So, for a person whose blood sugars have normalized and has lost weight with a GLP1RA, should we stop the GLP1RA, but continue it for another person who has lost weight with GLP1RA but never had diabetes? This makes no sense. Both people are benefitting from the GLP1RA-facilitated weight loss, so I would recommend that both should continue treatment. Several of the GLP1RAs have importantly shown the ability to reduce cardiovascular risk (eg heart attack and stroke risk) in people with type 2 diabetes. So, for a person who has cardiovascular disease and whose diabetes control becomes really great with the GLP1RA, should I recommend to stop treatment? Again, my recommendation is to continue. (Side note: the emerging GIP/GLP1 dual agonist tirzepatide (first in this new class of medication) also has excellent weight loss and glucose lowering capacity, but is not yet approved in Canada.)
The SGLT2i’s are medications that were originally developed to treat type 2 diabetes, but have since shown to have other powerful benefits, in people with or without type 2 diabetes, including treating heart failure, and providing powerful kidney protection. They also provide robust blood pressure improvement, and some weight loss. So again, I ask: In my patient whose diabetes control has become really good with an SGLT2 inhibitor, has lost some weight, feels better, and is protected against heart failure, should I stop the medication to see if the blood sugar control can stay in the normal range? Again, I find myself in disagreement with this strategy in most cases.
Bariatric surgery is a different story. Here, the hormonal changes (with gastric bypass or sleeve gastrectomy) that improve sugars and counteract our natural biology’s drive to defend weight are in place permanently, so if diabetes remission is achieved (as it often is), great! (though consideration of whether SGLT2is should be kept on board for other reasons should still be considered).
While remission of type 2 diabetes can be achieved with substantial lifestyle-induced weight loss, particularly in the early years of type 2 diabetes, it is very difficult for most people to keep this weight off long term, due to the natural human biology that drives weight regain.
Before stopping GLP1RAs or SGLT2i’s to see if diabetes is in remission, first consider if there are other health benefits for which these medications should be continued.
If diabetes remission is attained, monitoring of A1C must continue lifelong, as diabetes often comes back. Diabetes can return even if lifestyle changes and weight loss are maintained. Even after remission with bariatric surgery, about 50% of type 2 diabetes recurs at about 5 years postop. The Consensus Statement recommends monitoring A1C every 3-12 months.
Even after diabetes remission, the complications of diabetes can still occur, so routine monitoring for diabetes complications must continue (including eye checks, kidney health checks with blood and urine testing, foot checks, and so forth).
Disclaimer: I am/have been a research investigator in clinical trials of tirzepatide (Eli Lilly), liraglutide and semaglutide (Novo Nordisk). I receive honoraria as a continuing medical education speaker and consultant from the makers of tirzepatide, liraglutide and semaglutide .
Check me out on twitter! @drsuepedersen
Share this blog post using your favorite social media link below!
www.drsue.ca © 2022