Trends in diabetes treatment are changing rapidly.

In its 2022 guideline, the American Diabetes Association (ADA) recommended that sodium-glucose cotransporter (SGLT)-2 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) be prescribed as early treatment for people with type 2 diabetes because these therapies have shown cardiovascular risk reduction benefits.

Earlier, the Korean Diabetes Association (KDA)'s 2021 guideline also included GLP-1 RA in the list of preferred drugs for people with atherosclerotic cardiovascular disease and chronic kidney disease.

These examples show the growing importance of SGLT-2 and GLP-1 RAs in diabetes medication.

Against this backdrop, Novo Nordisk's GLP-1 RAs Ozempic (semaglutide) and Rybelsus (semaglutide) won regulatory approvals in Korea last year. The former is a once-weekly injection, and the latter is the world's first oral GLP-1 RA.

Korea Biomedical Review sat down with Professor IIdiko Lingvay of UT Southwestern Medical Center to learn more about the rapidly changing landscape of type 2 diabetes treatment and the advantages and disadvantages of emerging oral GLP-1 RAs.

Question: What is the role of GLP-1 RA in treating type 2 diabetes?

Answer: GLP-1 RAs are therapeutic agents that achieve the treatment goal of weight loss and lowering blood sugar. In real-world practice, GLP-1 RA is often prescribed because of its rapid effectiveness, especially if the patient is overweight or obese at diagnosis.

Guidelines also recommend early intervention to help patients achieve their treatment goals quickly. However, they also emphasize that treatment should be designed to help patients stay at target-achieving levels.

Q: Combination therapies are often used for early and potent treatment. What are agents that may synergize with GLP-1 RA?

A: Since metformin and SGLT-2 inhibitors have shown an additional effect on weight, their combination with GLP-1 RA will have an even greater effect. Due to the high cost of drugs in the U.S., sulfonylureas, which are relatively inexpensive (compared to SGLT-2 inhibitors), are also used.

Q: What are the clinical benefits of semaglutide in GLP-1 RA?

A: The biggest benefits of semaglutide are clinically proven blood sugar-lowering and weight-loss effects. Both effects are essential goals for diabetes treatment. But, of course, not all diabetes patients can solve their problems with this drug because diabetes is a very complex and progressive disease.

Nevertheless, I want to emphasize that semaglutide has a comprehensive effect compared to other therapies. Furthermore, based on the currently available data, it is also more effective than other GLP-1 RAs on the market.

For example, in both “SUSTAIN 7” and “PIONEER 10” studies comparing semaglutide and dulaglutide, semaglutide showed statistically significant improvements in glycemic lowering and weight loss in both oral and injection formulations.

Q: It's also noteworthy that there are oral and injectable medications based on a single ingredient of semaglutide.

A: Semaglutide sets itself apart from other oral diabetes medicines because it can produce the effects of injections with just pills. In terms of efficacy, too, I think it has the largest benefits of all oral diabetes medications currently available, in many ways, such as blood glucose lowering, weight loss, and hypoglycemic safety.

However, I prefer semaglutide injections. I know that some people have concerns about injections. But I have not met patients who refused semaglutide injections as long as they were properly and adequately educated about the injections.

This is because injections only need to be administered once a week, and the drug delivery system is very simple and convenient. In addition, from the patient's standpoint, injections are preferred because they are virtually painless, and patients don't need to take pills daily.

Q: Many patients are not comfortable with injections. Many Korean diabetics prefer oral medications.

A: We do have that problem in the U.S., too. But you have to distinguish whether it's a patient refusing (injections) or a healthcare provider not wanting to prescribe them.

In the U.S., there have been instances of primary care providers prescribing oral medications without asking patients first, assuming that they would not prefer injections.

Patients who have never used injections previously are wary of them. So, if you ask them if they would use oral or injectable medications, they will choose oral.

But if you fully explain the injectable, show them how to use it, let them use it, and then ask them after three or four months if they want to switch to oral, we've found that 95 percent of patients will stay on the injectable option.

If you can help them overcome their vague fears and worries about “injections,” the injections themselves aren't as much of a barrier for them. And in some cases, it may even be more convenient for patients in the long run.

Q: What are the challenges in the treatment of type 2 diabetes?

A: There is a group of patients for whom GLP-1 RA can play an important role but remains underutilized. These are patients with progressive kidney disease – those with an estimated glomerular filtration rate (eGFR) of 30 percent or lower.

These patients are at increased risk of hypoglycemia due to poor renal function but use insulin. GLP-1 RA is an ideal treatment for these patients because it lowers glycemic without the risk of hypoglycemia. In addition, patients taking a DPP-4 inhibitor or SGLT-2 inhibitor may also benefit from GLP-1 RA in glycemic control.

There are so many situations where GLP-1 RA can demonstrate its unique advantages. We believe that GLP-1 RA will improve the diabetes care landscape if used more actively.