More than 34 million people in the U.S. have diabetes, reports the Centers for Disease Control and Prevention.

Of these, the vast majority have type 2, or a reduced ability of their bodies to effectively process sugar in foods into energy for life.

Most people with type 2 diabetes have multiple considerations – including heart and kidney health, impact on weight, side effects and cost – when choosing the most appropriate medication to lower their blood sugar levels. The American Diabetes Association recommends starting with metformin first, but other medications including insulin often need to be added as the disease progresses.

Individual care plans will vary. But the guidelines provide evidence-based recommendations for each additional medication that should inform choices. Rozalina McCoy, M.D., an endocrinologist and internal medicine physician at Mayo Clinic, wanted to find out if older people with type 2 diabetes are getting the best medications for their situation. A new study published in JAMA Network Open, shares her research findings.

"In the last few years, research has shown that in order to improve health outcomes for people living with diabetes, it is important not only to keep blood sugar within a safe range — not too low or too high — but also to carefully select the medications that we use to do this," says Dr. McCoy.

Two diabetes prescriptions that have benefits beyond lowering blood sugar are GLP-1 receptor agonist (GLP-1RA) and SGLT2 inhibitor (SGLT2i) medications. For example, GLP-1RA medications reduce the risk of cardiovascular events, kidney disease and death; SGLT2i drugs reduce the risk of heart failure, kidney disease and death; and both have a significantly lower risk of hypoglycemia (low blood sugar) than sulfonylureas and insulin, according to Dr. McCoy. A third class that can be used in addition to metformin is the DPP-4 inhibitor class, which does not have the beneficial heart, kidney, or mortality benefits, but is still safe to use and does not cause hypoglycemia.

"Sulfonylureas have been in use for a long time and are inexpensive. But they are not always the right choice when considering the patient’s clinical situation and highest threat to their health and life," she says. Because of that, the researchers wanted to know if people were getting the individualized care possible with the newer medication classes.

Metformin also has a low risk for hypoglycemia. The medications of interest to the researchers in this study would generally be added to metformin therapy if necessary.

Guidelines versus real life

"Diabetes is one of the most common serious chronic health conditions, and disproportionately affects racial and ethnic minorities," she says. "Our research and the work of others has consistently demonstrated that Black and Hispanic individuals, and lower income individuals of any race, are less likely to receive guideline-recommended treatments for their diabetes and more likely to experience severe hypoglycemia or hyperglycemia events."

To examine how factors other than science influence treatment choices, Dr. McCoy, and colleagues from several institutions, used the OptumLabs Data Warehouse, a large collection of deidentified administrative claims data for people across the United States. OptumLabs is a collaborative center for research and innovation co-founded by Optum Inc. and Mayo Clinic, and focused on improving patient care and patient value. In this work, Dr. McCoy was interested in the impact of insurance type on the choice of medication, focusing on the differences between patients with private insurance and those with Medicare Advantage insurance.

The team reviewed the records for 382,574 adults, ages 58-66, who received medication for type 2 diabetes, between 2016-2019 – the time period immediately after which the heart and kidney benefits of GLP-1RA and SGLT2i classes became. Among this group, 45% (172,180) had Medicare Advantage insurance coverage and the rest had commercial insurance.

Over the study period, prescriptions for all three types of medications increased among both groups. However, commercially insured patients were much more likely to receive the medications protective to the heart and kidneys (GLP-1RA or SGLT2i) than patients with Medicare Advantage health insurance, even though both types of insurance offered these medications with the same level of coverage. By the end of the study period:

• Only 11% of Medicare Advantage patients were receiving GLP-1RA medications compared to 20% of commercially insured.
• A similar discrepancy was observed among patients receiving SGLT2i medications, 8.5% versus 18%.

The use of DPP-4i medications was also divided, with only about 8% of Medicare Advantage patients receiving these, compared to nearly 12% of those commercially insured.

Cost appeared to be one potential factor preventing use of GLP-1RA and SGLT2i medications, which are substantially more expensive than other medications used to manage blood sugar. Dr. McCoy and her colleagues found that the GLP-1RA and SGLT2i type medications were started more commonly by patients with annual incomes of at least $200,000 compared to those earning less than $40,000. Furthermore, twice as many Medicare Advantage patients were more at or below the $40,000 income level than those with commercial insurance.

"Some of the treatment differences may be attributed to physicians seeking to keep costs lower for their patients or patients simply not being able to afford the out-of-pocket co-copays for drugs that were, in theory, covered for them," says Dr. McCoy. "Patients with commercial insurance may have an easier time affording these costly medications because they can use manufacturer savings cards, which are not available to people with government insurance like Medicare or VA insurance.”

The research team found additional disparities with no obvious connection to medical necessity:

• Women were more likely to start GLP-1RA medications than men, but less likely to receive SGLT2i type medications.
• Black, Hispanic, and Asian patients were less likely to start GLP-1RA treatment than Caucasian, non-Hispanic patients.
• Non-white patients were more likely to start DPP-4i therapy, even if they would have benefited from other medications that lowered risks of cardiovascular and kidney disease.

Pursuing equity in diabetes management is important to Dr. McCoy. "We cannot achieve the goals of better health, better diabetes control, and fewer diabetes complications and deaths, if we do not address these disparities."

Getting medications to patients who need them

Another concerning finding of Dr. McCoy’s work was that people with additional health conditions that might indicate preferential use of GLP-1RA or SLGT2i medications were not consistently receiving them. In fact, they were sometimes less likely to receive them.

• Patients with nephropathy (kidney complications) were more likely to receive GLP-1RA than patients without nephropathy, but less likely to start an SGLT2i.
• Patients with a previous heart attack or cerebrovascular disease (including stroke) – who would especially benefit from GLP-1RA therapy – received it at the same rate as patients with no heart attack and less often than those without cerebrovascular concerns.
• Patients with heart failure, who would benefit from SGLT2i therapy, were less likely to receive it than those without that risk. And although DPP-4i medications are not recommended for these patients, they were more likely to receive them.

Awareness about the benefits of the different medication classes is key to improving their use. "The vast majority of diabetes medications are prescribed and managed by primary care clinicians," says Dr. McCoy. "In our study, family medicine and internal medicine doctors were much less likely to prescribe SGLT2i and GLP-1RA medications than endocrinologists."

In addition to becoming more familiar with the different types of glucose-lowering medications and treatment guidelines, Dr. McCoy reminds her colleagues there is more they can do.

"I think it is important for all clinicians, and especially generalists, to be aware of cost-related barriers to medication use and managing diabetes. These barriers affect all people with diabetes, not just those who are uninsured or underinsured," she says. "There are things we, as clinicians, can do to help. We can direct patients to assistance programs, become knowledgeable in insurance specifics and formulary design, and engage other care team members to assist us in supporting our patients. We need to identify ways to deliver the right care, to the right patient, in the right way, and at the right time. This means ensuring that every patient, no matter their age, race, gender, or insurance status can live well with their diabetes."

The multidisciplinary team that conducted this research included other collaborators from Mayo Clinic, as well as the University of Minnesota, and Yale-New Haven Hospital, New Haven, Connecticut. Full participant, affiliation and funding information can be found in the paper. This research is supported by the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, which seeks to transform the experience of health and health care delivery for Mayo Clinic patients, and people everywhere.

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