Use of newer type 2 diabetes drugs gives hope, but costs care

There is a trend toward increased use of newer glucose-lowering drugs with cardiovascular benefits, raising hopes for better outcomes in patients with type 2 diabetes, but with concerns about the high cost of the drugs, researchers say.

Two new studies examine this relatively recent trend in diabetes prescribing.

In one study, the use of newer non-insulin glucose-lowering drugs with cardiovascular and renal benefits began to increase after 2014, while at the same time the use of older human insulins was almost completely replaced by newer expensive analogues. This study was a cross-sectional analysis of the 2003-2018 US National Health and Nutrition Examination Survey (NHANES).

The other study, of nearly 15,000 patients with type 2 diabetes in 37 countries, found that use of newer agents, such as sodium glucose cotransporter 2 inhibitors (SGLT2) and glucagon-like peptide-1 (GLP-1) receptor agonists, increased. , but remains suboptimal in those who can benefit most from it.

It’s complicated

Taken together, the data underscores “the challenges we face when trying to manage diabetes, not just as a disease of hyperglycemia, but as a disease of hyperglycemia and increased micro- and macrovascular complications,” Rozalina G. McCoy, MD, an associate professor of medicine at the Mayo Clinic, Rochester, Minnesota, told: Medscape Medical News

“If we simply think of diabetes as a condition where we need to lower blood glucose levels, it makes sense that we would use the cheapest option available,” she added.

“But it’s much more complicated than that, and it’s not just about lowering blood sugar, it’s about reducing cardiovascular events, decreasing the progression of kidney disease and preventing death. The only two drug classes that have been proven What they do in type 2 diabetes are GLP-1 agonists and SGLT2 inhibitors, and they’re expensive drugs,” she said.

McCoy was not involved in either study, but has done similar research.

Generic drugs are coming online, but are not yet widely available. But even if they are – and this must also mean putting them on forms [in some countries, such as the United States] — they will still only be part of the solution, McCoy believes.

“As with insulin, I think generics are part of the solution, but so is reducing the cost of branded drugs… We definitely don’t want patients to bear the financial burden of their diabetes management, but we would. “This comes at the cost of not giving them evidence-based therapies that will improve their health. We really need to lower the cost of these drugs to make them affordable and accessible to patients and healthcare providers,” she said. .

Human insulin can be used safely in type 2 diabetes

The NHANES study, recently published in the Journal of General Internal Medicine by Phuc Le, PhD, of Cleveland Clinic Community Care, Ohio, and colleagues, included 7,394 representative US patients with type 2 diabetes.

Their use of inexpensive non-insulin drugs (which are available with at least one generic) increased from 37% in 2003-2004 to 54% in 2013-2014 (p < .001) and then stabilized.

For expensive non-insulin drugs (all others), use decreased from 2003-2004 to 2013-2014 and then slowly increased until 2017-2018, although not significantly (p = .247). The use of metformin and dipeptidyl peptidase 4 (DPP-4) inhibitors increased from 2003-2004 to 2017-2018, while the use of sulfonylureas and thiazolidinediones decreased significantly. Use of other non-insulin glucose-lowering drugs was low during the study periods.

However, Le and colleagues note, “with the ADA’s latest recommendations to use GLP-1 agonists and SGLT2 inhibitors for patients with cardiovascular disease, heart failure and chronic kidney disease, the overall use of expensive non-insulin drugs is likely to increase.” continue to increase for the foreseeable future, as they will not become generic for at least 10-15 years.”

In contrast, the use of cheap human insulin decreased from 7% in 2003-2004 to 2% in 2017-2018 (p < .001), while the use of expensive analog insulin increased from 4% to 16% over the same period.

Le and colleagues say this finding is “worrying” because of the rapid rise in the cost of analog insulin over the past two decades.

“Human insulin, which is 90% cheaper than analogues yet equally effective at glucose control for type 2 diabetes, saw a steep decline in use over the study period. The use of insulin analogues, promoted by their manufacturers as safer and more convenient This trend looks set to continue in the coming years as younger generations of physicians are not trained to prescribe human insulin,” the authors write.

McCoy echoed that concern, noting, “We can use human insulin in type 2, but it has to be dosed correctly and fit the patient’s life… They are used very differently than analogues.”

In particular, McCoy said that for some patients with type 2 diabetes who only need basal insulin and who have regular routines, a single bedtime dose of NPH, an intermediate-acting human insulin, may be effective.

Importantly, she warned clinicians not to “demonize” the older human insulins to patients, because if they have financial problems, they might just buy them from Walmart without telling their doctor and use them as the analog was prescribed without having to buy them. realize there is a difference.

“That’s very dangerous. I want us as clinicians to be familiar with using human insulins so that when we need to use them, we can do it effectively and safely,” she said.

But at the same time, McCoy emphasized, “we need to make analog insulin more affordable.”

The use of the expensive drugs was significantly higher for non-Hispanic whites than for other racial and ethnic groups, while the use of cheap drugs did not differ by race/ethnicity. Individuals with health insurance were twice as likely to use expensive drugs as compared to those without health insurance.

Globally, the use of newer drugs is increasing, but is still sub-optimal

The global study was recently published online in BMC endocrine disorders by Suzanne V. Arnold, MD, of Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, and colleagues. It was part of DISCOVER, a prospective, observational study of 14,575 people with type 2 diabetes who initiated second-line therapy from 37 countries in Africa, the Americas, Europe, the Middle East, Southeast Asia, and the Western Pacific. .

At enrollment in 2014-2016, 8.7% of participants were started on an SGLT2 inhibitor, 2.1% on a GLP-1 agonist and 0.1% on both, increasing to 12.8 respectively within 3 years. %, 2.6% and 0.7%.

Factors that increase the likelihood that you are taking an SGLT2 inhibitor or GLP-1 agonist included the presence versus absence of coronary artery disease (20.0% versus 13.8%), heart failure (22.5% versus 14, 1%) and chronic kidney disease (17.1% vs. 14.4%) (all p < .001). In contrast, use was similar for those with versus without cerebrovascular disease (14.7% versus 14.5%; p = 0.18) and peripheral arterial disease (14.9% vs. 14.5%; p = .11).

The median use of both classes was 19% in all countries, but varied by region, with remarkably low rates in Africa and Asia and a trend towards higher use in wealthier countries. Countries with particularly high usage rates were Kuwait, the United Arab Emirates, Costa Rica and Norway. (Neither the United States nor the United Kingdom were included in this study.)

The use of SGLT2 inhibitors and GLP-1 agonists was 10.4% in patients with type 2 diabetes treated by general practitioners, 16.9% for endocrinologists, 26.1% for cardiologists and 22.0% for other specialists .

Increased use of both classes was significantly associated with younger age (odds ratio [OR]0.77 per 10 year increase), male gender (OR, 1.17) and higher body mass index (OR, 1.51 per 5 kg/m2

SGLT2 Inhibitors and GLP-1 Agonists Not on the WHO List

McCoy noted that, as of now, neither SGLT2 inhibitors nor GLP-1 agonists are included on the World Health Organization’s list of essential drugs, which dictates availability to low- and middle-income countries.

“I’d like to see the day when sulfonylureas are off the list and SGLT2 inhibitors are on…Currently, they’re being used in wealthier countries by wealthier people seeing specialists,” McCoy said.

But, she noted, “at least in other countries, people with comorbidities are more likely to get them, as opposed to the United States. Here it’s more about access than indication.”

The DISCOVER study program is funded by AstraZeneca. McCoy has reported being an advisor to Emmi in developing educational materials for diabetes and prediabetes patients. Le and Arnold have not reported any relevant financial relationships.

J Gen Intern Med. Published online April 28, 2022. Summary

BMC Endocr Disorder. Published online April 26, 2022. Full text

Miriam E. Tucker is a freelance journalist based in the Washington, DC area. She is a regular contributor to Medscape, and other work appears in The Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She’s on Twitter: @MiriamETucker.

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