Q&A: Medication plus lifestyle strategies best for type 2 diabetes prevention
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Key takeaways:
- Providers should consider prescribing pharmacotherapy in addition to lifestyle modification for adults with prediabetes.
- More trials are needed to analyze the effects of newer medications in prediabetes.
Providers should focus more on using pharmacotherapies in addition to lifestyle intervention to prevent progression from prediabetes to type 2 diabetes, according to two researchers.
In a review article published in Frontiers in Endocrinology, the authors described how strategies for preventing type 2 diabetes have become a bigger focus in recent years. Preventing diabetes involves a multifaceted approach, with lifestyle modification and medication both needed to achieve the best results, according to study co-author Priyanka Majety, MD, assistant professor of internal medicine and adult outpatient diabetes director in the division of endocrinology, diabetes and metabolism at Virginia Commonwealth University Health System.
“I cannot emphasize enough the importance of sticking to lifestyle modification,” Majety told Healio. “It is the cornerstone for every patient with prediabetes and diabetes. If we take away the medications and they aren’t adhering to the lifestyle modifications, they lose all the benefits.”
Newer medications such as GLP-1 receptor agonists and the dual GIP/GLP-1 receptor agonist tirzepatide (Mounjaro, Eli Lilly) are changing the way providers treat type 2 diabetes and obesity, according to study co-author Dinesh Edem, MD, DABOM, assistant professor of internal medicine and endocrinology at University of Arkansas for Medical Sciences (UAMS) College of Medicine and director of the medical weight management program at UAMS Health. However, while many drug trials and studies focus on treating type 2 diabetes, Edem said, prevention is just as important due to the rising number of diabetes cases in the U.S.
“Diabetes has a 12% incidence and prediabetes has a 38% incidence,” Edem told Healio. “That is a combined significant burden on American health care. The cost of diabetes management is around $327 billion per year in the U.S. Reversing diabetes and preventing type 2 diabetes is of major importance. The epidemics of prediabetes and diabetes are parallel to the obesity epidemic. Promoting healthy behaviors that help lose weight will prevent type 2 diabetes and also reverse prediabetes.”
Though multiple FDA-approved options are available for people with type 2 diabetes or obesity, most of these options are unavailable for adults with prediabetes. Edem and Majety said more studies need to be conducted on the effects of pharmacotherapy among people with prediabetes to expand access to medications for those who need them and potentially slow the increasing incidence of type 2 diabetes in the U.S.
Edem and Majety spoke with Healio about the evidence surrounding pharmacotherapies and prediabetes, what providers should do when treating adults with prediabetes and what types of studies still need to be conducted.
Healio: Why is it so important to review the impact of pharmacotherapies on type 2 diabetes prevention?
Edem: The obesity epidemic is leading to an increase in diabetes and prediabetes incidence. We all know that diabetes comes with a host of complications. However, prediabetes can also cause complications like retinopathy and neuropathy. I consider prediabetes as a mild form of diabetes. My HbA1c goal is less than 5.7%, not 6.5%. Prediabetes is a great opportunity for me to tell my patients that you're already at risk for complications. That’s why this review will emphasize the options available to the patients who want to avoid type 2 diabetes. Bariatric surgery is the most efficacious for weight loss, but is not an option for the majority of people. Lifestyle changes are essential, but most patients may not be able to sustain these in the long run. These medications and pharmacotherapies can help boost the efforts that patients are actually taking.
Healio: Is there any strategy that is best for preventing type 2 diabetes?
Majety: The first and foremost is lifestyle modification. We have large numbers of studies like the Diabetes Prevention Program or the Finnish Diabetes Study that found lifestyle modifications can reverse or slow the progression of type 2 diabetes.
The medications with the most evidence are older medications that have been here for a while. Metformin has been around, a lot of patients are on it, so we just have more data about metformin slowing the progression of type 2 diabetes. There is emerging evidence that GLP-1s and the dual GIP/GLP-1 tirzepatide, by means of weight loss, will slow the progression of type 2 diabetes.
Patients who have obesity or have a higher weight are at higher risk for diabetes development. The ability of a medication to prevent progression or slow progression depends on how much weight loss that patient achieves. It is a balance, because sometimes at higher doses the patients may not be able to tolerate these medications. It’s all proportionate to the weight loss that the drug is helping them achieve.
Healio: What did your review find about other suggested therapies such as vitamin D and testosterone for preventing type 2 diabetes?
Majety: There is very limited evidence on medications that are not typically used for treating type 2 diabetes. Vitamin D deficiency is very prevalent. The hypothesis that vitamin D status may influence the risk of type 2 diabetes is plausible only because both impaired pancreatic function and insulin resistance, which are cornerstones for the pathophysiology for type 2 diabetes, anecdotally have been reported in patients with low vitamin D levels. There is some observational data that show that low vitamin D status may be associated with risk of development of type 2 diabetes. But these are not robust, randomized controlled trials. That’s why the Vitamin D and Type 2 Diabetes (D2d) study was conducted. When they did this large randomized controlled trial, there was no significant reduction in type 2 diabetes risk.
Edem: With testosterone, there was a study called T4DM published in 2021, which was a double-blind study in which one group of patients were getting testosterone and the other group were not getting the testosterone, or the placebo group. In that study at the end of 2 years, patients who were not on testosterone had a 21% incidence of type 2 diabetes vs. a 12% type 2 diabetes incidence in the testosterone group. It has something to do with increasing muscle mass, reduction in weight, improvement in insulin resistance, but with side effects like increasing hematocrit. Testosterone itself is not FDA approved for improving glucose metabolism as further studies need to be done to investigate the effect of testosterone on type 2 diabetes.
Healio: Do you think enough providers are discussing type 2 diabetes prevention with patients?
Majety: A limitation is that we do need larger studies looking at this question of prevention specifically and not just treatment of diabetes so that we can get these FDA approved. Right now, these medications are not approved [for prediabetes], so it’s very hard for us physicians to get these medications covered for patients, even if we think they’re good candidates.
Edem: In the STEP-2 trial, HbA1c levels were less than 6.5% in 68% of the semaglutide (Wegovy, Novo Nordisk) 2.4 mg group vs. 15% of the placebo group. But now, due to cost and supply chain issues, insurers are not ready to cover these amazing medicines to prevent diabetes. We’re seeing it covered only if the diabetes gets worse. Patients who actually need it are not getting these medications. If you want to address the root problem of the situation, which is obesity and the progression to type 2 diabetes, these new age medicines are doing a great job.
Healio: Are there other key barriers that are preventing people with prediabetes or those who may be at risk for type 2 diabetes from accessing these medications?
Edem: About 30% of all diabetes cases are undiagnosed. The patients don’t even know they are diabetic. Just imagine how many patients with prediabetes are undiagnosed. We are underestimating the incidence of prediabetes. We need to a better job of diagnosis and then making them aware of all of these options, not just lifestyle [interventions]. Right now, we just have metformin and lifestyle changes, which are good, but they’re not better compared to the newer medicines that we currently have. We need specific trials for the specific diagnosis of prediabetes and see the change in incidence. We know that the newer medications will do a great job in preventing type 2 diabetes. But it’s about convincing the providers, the patients, the insurers, everyone to provide these medications based on robust large-scale trials.
Healio: Are there any other future studies or areas of research that need to be addressed?
Majety: This is an evolving area right now. After we published our review paper, there was another group led by W. Timothy Garvey, MD, FACE, MABOM, that [published] a post hoc analysis looking at tirzepatide to see if it reduced the risk of developing type 2 diabetes, and it absolutely does. Like we were discussing, it’s proportionate to the dose, a higher dose means higher weight loss and better prevention of type 2 diabetes. We have good evidence from subanalyses and post hoc analyses that these medications are amazing, and they can help to prevent type 2 diabetes, but we need that specific question in a randomized controlled trial just looking at patients at higher risk, giving them these medications and then following them long term to see if these medications truly decrease the incidence of type 2 diabetes.
Edem: The STEP 10 study is looking at how well semaglutide works in people with obesity and prediabetes, and we are awaiting results. Currently, I think we’re missing out on treating this large pool of patients with obesity and prediabetes, where these medicines can be studied and go on to FDA approval. These medications would be most beneficial for these patients.
For more information:
Dinesh Edem, MD, DABOM, can be reached at dedem@uams.edu.
Priyanka Majety, MD, can be reached at majetypriyanka@gmail.com.
Reference:
- Majety P, et al. Front Endocrinol. 2023;doi:10.3389/fendo.2023.1118848.
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