Less than two weeks before the 82nd Scientific Sessions of the American Diabetes Association, new data from the Diabetes Prevention Program Outcomes Study (DPPOS) provided insights into 21 years of follow-up from more than 3,200 adults with prediabetes. As with previous data releases from the program, the new data attracted a lot of attention, and for many, it was because the findings went against conventional wisdom: Neither lifestyle interventions nor metformin reduced the risk of cardiovascular disease among these patients.
Both of these methods have been shown to offer benefit in reducing the risk of developing type 2 diabetes, metformin and lifestyle interventions have proven themselves as an integral part of treatment algorithms for many patients with diabetes. However, in recent years the focus has been placed on not only addressing substandard glycemic control in diabetic patients, but also addressing the inherent cardiovascular and renal risks in these patients through the use of newer agents, such as GLP-1 receptor agonists and SGLT2 inhibitors.
With that in mind, endocrine network Three experts in diabetes and cardiac metabolism asked what they thought of the recent data from DPPOS and whether it was time to move away from metformin as a first-line treatment for type 2 diabetes toward a newer agent or agents. The responses of these experts, Juan Frias, MD, of the National Research Institute, and. Timothy Garvey, MD, of the University of Alabama at Birmingham, and Hedo Herspink, MD, PhD, of the University of Groningen in the Netherlands, can be found below.
Is it time to rethink metformin as a first-line treatment? Entering the era of personalized medicine
Juan Frias, MD: This is an excellent question. My answer would be that metformin is very inexpensive, often free, and very effective in lowering glucose. In your patients, especially patients with very high glucose, you usually get a larger drop, but this is known for any drug that can work very well from a glycemic perspective with metformin.
What I would say is that we should not use metformin and delay the use of those agents, such as a GLP-1 inhibitor or an SGLT2 inhibitor, in patients who are appropriate and need those agents. Therefore, do not use metformin, excluding the use of another agent. I think it can definitely be of help to a lot of patients as it clearly improves glycemic control. Again, it’s generic, inexpensive, and I would say it will continue to be used. Sulfonylureas have continued to be used, and I definitely think they should be phased out before I phase out metformin.
Therefore, we just need to ensure as the guidelines tell us, regardless of HbA1c and regardless of metformin use, that patients with atherosclerotic cardiovascular disease who are at high risk should use GLP-1 receptor agonists or SGLT2 inhibitors with cardiovascular disease installed. benefit. In patients with heart failure, SGLT2 inhibitors should be used. In patients with chronic kidney disease, an SGLT2 inhibitor is often a combination of an SGLT2 inhibitor and a GLP-1 receptor agonist and I think metformin is OK to include there. What you don’t want to do is take metformin for 1-2 years and not add those other agents.
W Timothy Garvey, MD: Well, that’s a good question. But there is a subanalysis of the DPP data looking at patients who lost 10% or more of their body weight, and this subgroup has lower MACE outcomes: myocardial infarction, nonfatal stroke, and the composite cardiovascular outcome measure. Therefore, these data suggest that it boils down to achieving adequate weight loss to achieve cardiovascular protection. We don’t have this data from these weight loss drugs at this time.
There’s a study called SELECT going on with semaglutide 2.4, non-diabetic patients, but, again, we probably won’t have this data for a few years. I also believe there is a trial of cardiovascular outcomes in diabetic patients under treatment for tirzepatide. Again, we are only waiting for this data, but if we can demonstrate that these medications, combined with lifestyle-related interventions, have achieved sufficient weight loss to put them in the range where we can expect to see heart disease prevention, it may and should be Game changer.
I think in terms of how we think about these patients, we need to help increase patients’ access to these evidence-based treatments, which are currently somewhat limited for obesity. Perhaps, with this data showing the degree of weight loss, and how that weight loss translates into prevention, or treatment of obesity-related complications, I think taxpayers and health care systems would be more amenable to making these treatments available to patients.
Hiddo Heerspink, MD, PhD: I think it’s time to think about preventing complications of type 2 diabetes or prediabetes. Metformin is a great drug for reducing hyperglycemia, but the outcome data, as I mentioned, is limited. We have great outcome data with SGLT2 inhibitors and great outcome data with GLP-1 receptor agonists.
So, in my view, it is really time to rethink our approach to therapy and the sequence of pathways. As I mentioned earlier, I think it’s about preventing results. It is also not the prevention of diabetes or new diabetes and we have data from SGLT2 trials with non-diabetic patients that SGLT2 inhibitors reduced the onset of new diabetes by more than 33%.
So, it’s really important to take that into account and rethink our approach. Our approach has traditionally been around when drugs come to market and we’ve always added all the new drugs but now with so many new drugs showing cardiovascular benefits, it’s time to consider any group of patients. So, we’re really heading into the personalized medicine field that I’ve had in the near future.
These texts have been edited for length and clarity.