Remission of type 2 diabetes - Is it worth the effort?

When I started as a GP just shy of 20 years ago, type 2 diabetes (T2DM) was viewed as a progressive disease that, at best, could be managed, but not reversed. Management was based around the relatively simple armoury of metformin, gliclazide and insulin. Not any more….

Along side the multiple novel drugs available, notably the SGLT2 inhibitors and GLP1 agonists which have been shown to provide cardio-renal protection, we also have a better understanding of how T2DM evolves. Importantly we now know that this is a disease that can be reversed by removing visceral fat which allows return of normal hepatic and beta cell function and restoration of normoglycemia. 

Triggered in large part by the DiRECT trial, evidence has been accumulating that for people with T2DM remission into a non-diabetic state is possible with rapid weight loss (in general >10kg), initially with very low calorie diets followed by food reintroduction and weight maintenance. Recent real world NHS data supports the DiRECT study findings, and has led to a roll out of the ‘soups ands shakes diet’ across the NHS. 

But losing and maintaining that weight loss, even with good support, is incredibly hard. And, as we often (rightly) pick up on with diabetes research, drops in Hba1c are ultimately only a surrogate marker. And we know for many people, even if they manage to induce diabetes remission, weight gain may occur and a transition back into a diabetic state. So the question is: ’Is it really worth all that effort?’. If they induce remission then revert back into a diabetic state, is this going to improve clinically significant endpoints, not just a temporary drop in Hba1c? 

The hope is that inducing remission, even if temporary, would lead to a reduction in diabetes related complications. Data supporting this has been slim, in part due to the fact that the concept of diabetes remission is relatively new. But a new study published in the last year (PLoS ONE 2023;18) and reviewed as part of the NIHR alerts in the BMJ 2024;384:q516 gives added weight to this theory. 

This was a retrospective cohort study based on UK primary care data of >60,000 people with T2DM comparing diabetes related complications (microvascular, macrovascular, CVD events and all cause mortality) over a 7 year period. The authors identified 4 ‘trajectories’ of patients:

• Group 1 - those who induced remission of T2DM but then reverted to a diabetic state (effectively the ‘intervention group’ we are wanting to look at).
• Group 2 - those who gradually reduced Hba1c levels but never got into remission (akin to our previous ‘standard’ model of care).
• Group 3 - those who had high maintained Hba1c levels without reduction (the reference group).
• Group 4 - those who had maintained low Hba1c levels in the remission range.

Unsurprisingly group 4 (maintained low Hba1c) came out best with the most significant reductions in both macro and microvascular complications (although there was a ‘quirk’ in that group 4 had slightly higher mortality rates, thought due to a proportion of people who will have lost significant weight unintentionally due to other illnesses e.g. cancer, which skewed this result). 

But the interesting results are when we look at how group 1 (remission then rising Hba1c) did compared to group 2 (gradual reductions in Hba1c but no remission). Overall group 1 had lower rates of microvascular complications than group 2, and also had significant reductions in both macrovascular complications and CVD events, which group 2 didn’t. The authors conclude that even short periods of remission of 6 months can be enough to reduce micro and microvascular complications down the line, similar to the ‘legacy effect’ seen in the UKPDS trials which showed early tight control with medications (even with rising Hba1c later) can lead to lower complications many years later. 

As always with observational data confounding may be an issue - the authors did their best to adjust for variables but there were notable differences in baseline characteristics of the groups. Also the participants were mostly white, so may not be generalisable to other populations. 

So this is by no means definitive, and further studies will be needed to confirm these findings, but this data is very encouraging. Our message, for those people with T2DM who may be embarking on a remission plan, is that even if their remission is temporary this may lead to lower rates of CVD and microvascular disease down the line and yes, it probably is worth the effort. 

If you're looking to refresh your diabetes management skills, join us for the updated Diabetes for Primary Care course on Saturday, November 30th. We'll guide you through the journey from diagnosis, through the complexities of management, to complications. We will cover hot topics including the place of incretin-based therapies, new advances in diabetic kidney disease and the use of Continuous Glucose Monitoring in primary care. There will be plenty of case studies, interaction and quality improvement ideas leaving you upskilled and re-enthused around diabetes management.