ACP: Use GLP-1 agonists or SGLT-2 inhibitors as add-on therapies for type 2 diabetes
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Key takeaways:
- ACP released new recommendations on type 2 diabetes treatment.
- A presenter at the organization’s annual meeting broke down the new guidelines and rationale behind them.
BOSTON — New recommendations from ACP on type 2 diabetes treatment include adding a GLP-1 agonist or SGLT-2 inhibitor to therapy for patients who have inadequate glycemic control, the organization announced.
During her presentation at the ACP Internal Medicine Meeting, Carolyn Crandall, MD, MS, MACP, chair of the ACP clinical guidelines committee and a clinical professor of medicine at the University of California, Los Angeles, discussed “key points of the brand-new clinical guidelines regarding newer pharmacologic treatments for adults with type 2 diabetes.”
Crandall said the guidelines, which were based on an independent systematic review and meta-analysis, focused on several newer pharmacological treatments as add-on therapy: GLP-1 agonists, SGLT-2 inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors.
There are two new major recommendations. First, the ACP now recommends adding a GLP-1 agonist or SGLT-2 inhibitor to lifestyle modifications and metformin for adults with inadequate glycemic control to reduce the risk for morbidity and all-cause mortality.
“This is a strong recommendation based on high certainty evidence,” Crandall said.
Specifically, the guidance recommends using a GLP-1 agonist to reduce the risk for stroke, major adverse cardiovascular events (MACE) and all-cause mortality, and using an SGLT-2 inhibitor to reduce the risk for MACE, progression of chronic kidney disease (CKD) and all-cause mortality.
“The only newer pharmacological treatments for type 2 diabetes that reduce all-cause mortality compared to placebo or usual care are actually the SGLT-2 inhibitors and GLP-1 agonists, hence our recommendations,” Crandall said. “After evaluating the benefits and harms of SGLT-2 inhibitors and GLP-1 agonists, the guidelines committee was unable to determine the superiority of one of those two pharmacological classes over the other.”
The guideline committee also took cost into consideration. Crandall said “there were no substantial differences” between the two “that would warrant prioritizing one of those two pharmacological classes over the other.”
The second major recommendation is that the ACP now recommends against adding a DPP-4 inhibitor to lifestyle modification and metformin in this population. Again, this was a strong recommendation based on high-certainty evidence.
“Add-on DPP-4 inhibitors compared to usual care results in no difference in all-cause mortality, MACE, myocardial infarction, stroke, congestive heart failure (CHF), hospitalization, chronic kidney disease progression, or severe hypoglycemia,” Crandall said.
Crandall also offered some “clinical pearls.” She said clinicians should consider add-ons to metformin and lifestyle therapy if their patient has long-standing type 2 diabetes with glycosylated hemoglobin levels around 8% despite usual care. In the randomized controlled trials that the committee evaluated, the mean HbA1c range was “somewhere around 7.2% to 9.5%,” Crandall said.
“When selecting an additional therapy, clinicians should consider benefits, harms and costs of the medications, perform an individualized assessment of each patient's preference, glycemic control, target comorbid conditions and risk of symptomatic hypoglycemia,” Crandall said. “We should prioritize adding the SGLT-2 inhibitors in patients with type 2 diabetes who also have CHF or CKD, whereas we may prioritize adding GLP-1 agonists in patients with type 2 diabetes and an increased risk of stroke or for whom total body weight loss is an important treatment goal.”
References:
- Crandall C. New in Annals of Internal Medicine: Hear it first from the authors. Presented at: ACP Internal Medicine Meeting; April 18-20, 2024; Boston.
- Drake T, et al. Ann Intern Med. 2024;doi:10.7326/M23-1490.
Perspective
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Diabetes and diabetes-associated complications represent one of the leading causes of morbidity and mortality in the United States, and it is critical for individuals living with diabetes to have access to evidence-based therapies that will enable optimal diabetes management and prevention of serious complications. The ACP’s recently updated guidelines on the pharmacologic treatment of type 2 diabetes highlight the clinical benefits of adding SGLT-2 inhibitors or GLP-1 agonists to treatment regimens of individuals with inadequately controlled diabetes to lower the risk of major adverse cardiovascular events, stroke, progression of chronic kidney disease and all-cause mortality.
However, in order for patients to benefit from SGLT-2 inhibitors and GLP-1 agonists, they must be able to access these medicines. SGLT-2 inhibitors and GLP-1 agonists are expensive and can have high out-of-pocket costs depending on an individual’s health insurance coverage. Recent findings have shown that the manufacturing costs of these medicines are significantly lower than their market prices, yet their prices remain high. In addition, shortages of certain formulations of these therapeutics have been reported worldwide.
Previous data have also shown that there were lower rates of GLP-1 agonist use among individuals with lower household income and among Asian, Black and Latino individuals in the United States. Another recent study found that pharmacy dispensing of GLP-1 agonists remains lower for American Indian/Alaska Native, Asian, Black, Native Hawaiian or Pacific Islander, and Latino individuals compared to white individuals with type 2 diabetes, and pharmacy dispensing of SGLT-2 inhibitors was lower for American Indian/Alaska Native, Black and Latino individuals compared to white individuals with type 2 diabetes.
Further, individuals with diabetes must be aware that they have diabetes in order to access necessary treatments. The CDC estimates that over 20% of adults with diabetes in the U.S. are not aware of their diagnosis. This includes individuals who do not have access to regular medical care, as well as individuals who do have access to care, but have not been screened by their clinicians for diabetes. For example, certain Asian American subpopulations are at higher risk for developing diabetes at a relatively lower BMI and Native Hawaiians and Pacific Islanders are also at increased risk for developing type 2 diabetes at earlier ages, so it is important for clinicians to consider screening these individuals for diabetes at a lower weight and/or age to avoid a delay in diabetes diagnosis and ensure timely initiation of recommended management and treatment to avoid diabetes-associated complications. Efforts must also be made to link individuals without access to medical care with health care services, so that they can receive diabetes screening and access to necessary treatments.
Therefore, while GLP-1 agonists and SGLT-2 inhibitors have shown clinical benefits in the management of type 2 diabetes, particularly for individuals with CVD and chronic kidney disease with inadequately controlled diabetes, it will be important for clinicians to appropriately screen individuals for diabetes and to be aware of and routinely implement the updated diabetes treatment guidelines, so that individuals receive these prescriptions when clinically indicated. From a policy perspective, it is critical to ensure that individuals have access to necessary health care and that the costs of GLP-1 agonists and SGLT-2 inhibitors are more affordable, so that all individuals who would benefit the most from these medicines are able to financially access them to reduce disparities in health outcomes.
References:
- Barber MJ, et al. JAMA Netw Open. 2024;doi:10.1001/jamanetworkopen.2024.3474.
- Eberly LA, et al. JAMA Health Forum. 2021;doi:10.1001/jamahealthforum.2021.4182.
- National diabetes statistics report. https://www.cdc.gov/diabetes/data/statistics-report/index.html. Accessed May 14, 2024.
- Rodrigez LA, et al. Lancet. 2024;doi:10.1016/j.lana.2024.100759.
- Uchima O, et al. Prev Chronic Dis. 2019; doi:10.5888/pcd16.180187.
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Crandall C. New in Annals of Internal Medicine: Hear it first from the authors. Presented at: ACP Internal Medicine Meeting; April 18-20, 2024; Boston.
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