Pharm Fresh: What Pharmacological Solutions Could Play a Role in Preventing Diabetes?

For decades, physicians have maintained that type 2 diabetes could be delayed or even prevented altogether simply by modifying certain behaviors. Priyanka Majety, MD, talks to Endocrine News about pharmacological options that could help these patients, but lifestyle modifications are still crucial.

As we enter National Diabetes Month and head toward World Diabetes Day on November 14, the burden of type 2 diabetes remains huge – and daunting. The global prevalence of diabetes is estimated to be 463 million and projected to rise to 700 million by 2045, meaning a reduced quality of life and higher mortality for many people, as well as higher healthcare costs.

And while many trials like the Diabetes Prevention Program (DPP), the Finnish Diabetes Prevention Study, and the Da Qing Diabetes Prevention Program have shown that lifestyle modifications can prevent or delay the onset of type 2 diabetes, physicians find that many of their patients with diabetes have a hard time staying consistent and compliant with intensive changes.

Earlier this year, a mini review appeared in Frontiers of Endocrinology, titled “Pharmacological approaches to the prevention of type 2 diabetes mellitus.” As the title suggests, the authors cover various pharmacotherapeutic options to prevent type 2 diabetes, as well as the evidence behind their safety and efficacy.

“I strongly believe that prevention is better than cure, especially when it comes to type 2 diabetes,” says Priyanka Majety, MD, assistant professor in the Division of Endocrinology, Diabetes, and Metabolism at Virginia Commonwealth University in Richmond, and the first author of the Frontiers paper. “With the recent developments in the field of diabetes, there are medication options that can serve as effective adjunctive therapies to lifestyle changes to help our patients prevent the onset of type 2 diabetes. Our aim with this article was to present the latest evidence on the role of pharmacological interventions in the prevention of type 2 diabetes and to help clinicians identify the best options for their patients.”

Modifying Risk Factors

The authors of the Frontiers paper point out that the ability to prevent or delay type 2 diabetes by modifying some of its risk factors has been hypothesized for decades, since diabetes develops gradually, leaving open many opportunities for intervention.

Majety says that one of the stages before the onset of frank diabetes is impaired glucose tolerance. “Risk factors such as obesity, physical inactivity, and highly processed dietary habits play a role in the development of type 2 diabetes and these risk factors are modifiable,” she says. “Researchers have hypothesized that if interventions to target weight loss either with lifestyle changes (dietary modifications, increased physical activity) or medications at this stage (impaired glucose tolerance), diabetes can be prevented or at least delayed.”

And again, lifestyle modifications are what most physicians will start with when treating diabetes. Majety says that these modifications are the cornerstone of treating diabetes and obesity, because even with the recent pharmacological developments, if lifestyle changes aren’t in place, as soon as the medication becomes unavailable for whatever reason, progress can be lost.

Majety tells Endocrine News that one of the strategies that has worked for her to keep her patients motivated is understanding their goals and what’s important to them. “Some say they do not want all the complications that come with diabetes that they have witnessed with family members; some want to get healthy for their family, etc.,” she says. “Once I understand what is important to them, I help them come up with clear, realistic short-term goals. I try to involve family or friends who might be able to support them attain their goals. All the lifestyle changes need to start small, and I encourage them to incorporate into their daily routines if possible – some kind of movement while watching TV, etc. Finally, I tell them that setbacks are common and that it’s okay as long as they do not give up. Regular follow-ups and check-ins with the patients help a lot.”

Using Personalized Medicine

When that foundation is set, it is important to choose which medication is best for the patient. Metformin is one of the well-established medications Majety and her co-authors looked into as an option to prevent diabetes –ideal for most patients, but physicians need to make sure kidney and liver function is appropriate, and to choose the dose accordingly.

Then there are the GLP-1 receptor agonists that have been making headlines lately. They’re popular, which can sometimes make them hard to access, and they can increase the risk of pancreatitis, so Majety says that she and her co-authors had to ensure that patients had not had pancreatitis in the past before starting them on these medications. “We also ensure that there is no family or personal history of medullary thyroid cancer, which can be associated with a rare genetic syndrome called MEN (multiple endocrine neoplasia),” she says. “Some patients may have some nausea and abdominal discomfort when they start these medications, but they tend to improve with continued use. So, counseling them is very important and we have some tricks to help them with these unwanted effects if needed – start slow and go up on the dose slowly to give their body some time to adjust to the dose or try other medications in the same category.”

For Majety, it goes back to personalized medicine, which she points to as the future of medicine, especially for diabetes care. “Using the patient-specific characteristics to direct treatment strategies that are most effective for that individual is crucial,” she says. “This will ensure success for both us and our patients. We consider the type of diabetes they have, their lifestyle, their comorbid conditions and complications (heart disease, high blood pressure, kidney disease, hyperlipidemia, etc.) before choosing a medication. Thankfully we have so many options to consider for patients with type 2 diabetes.”

Majety says that she commonly prescribes GLP-1 receptor agonists and that the vast majority of her patients have benefited – they’ve achieved better control of their diabetes and hit weight loss goals. And while most patients tolerate the medication while titrating slowly, some have had unwanted gastrointestinal side effects. “We try a different medication from the same class, possible or dose and titrate it up very slowly if possible or keep it at the lowest dose which they can tolerate, etc.,” she says.

A Healthy Lifestyle is Key

The authors conclude that there are emerging data showing the benefits of these pharmacological therapies to prevent type 2 diabetes, but further studies are required. For now, Majety says this is an exciting time to be helping patients with diabetes and obesity. These medications have been shown to be safe and effective for weight loss, glucose control, and the management of diabetes complications, and now sub analyses from major studies have shown that newer classes of medications like GLP-1 receptor agonists and dual GLP-1 and GIP receptor agonists have the potential to reverse pre-diabetes and delay the risk of developing type 2 diabetes. However, Majety says, dedicated large-scale studies are needed to answer this question more specifically to understand their actual role in diabetes prevention.

For patients, Majety hopes they aren’t shy about asking for assistance. “There are options to help with pre-diabetes and potentially prevent or delay the onset of type 2 diabetes,” she says. “You may be a candidate for one of these medications. Do not hesitate to ask your providers for help. A healthy lifestyle is irreplaceable. None of the medications work as well if a healthy lifestyle is not in place.”

Bagley is the senior editor of Endocrine News. In the October issue he wrote about how understanding Hispanic traditions can improve treatment outcomes in “Cultural Connections.”