Two professional societies have issued new guidance for type 2 diabetes management in primary care, with one focused specifically on the use of the newer medications.
On April 19, 2024, the American College of Physicians (ACP) published Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. The internal medicine group recommends the use of glucagon-like peptide-1 (GLP-1) agonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors as second-line treatment after metformin. They also advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors.
The document was also presented simultaneously at the ACP annual meeting.
And on April 15, the American Diabetes Association (ADA) posted its comprehensive Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals as a follow-up to the December 2023 publication of its full-length Standards. Section 9, Pharmacologic Approaches to Glycemic Treatment, covers the same ground as the ACP guidelines.
General Agreement but Some Differences
The recommendations generally agree regarding medication use, although there are some differences. Both societies continue to endorse metformin and lifestyle modification as first-line therapy for glycemic management in type 2 diabetes. However, while ADA also gives the option of initial combination therapy with prioritization of avoiding hypoglycemia, ACP advises adding new medications only if glycemic goals aren’t met with lifestyle and metformin alone.
The new ACP document gives two general recommendations:
1. Add an SGLT2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control.
*Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.
*Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.
2. ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.
Both ADA and ACP advise using SGLT2 inhibitors in patients with congestive heart failure and/or chronic kidney disease, and using GLP-1 agonists in patients for whom weight management is a priority. The ADA also advises using agents of either drug class with proven cardiovascular benefit for people with type 2 diabetes who have established cardiovascular disease or who are at high risk.
ADA doesn’t advise against the use of DPP-4 inhibitors but doesn’t prioritize them either. Both insulin and sulfonylureas remain options for both, but they also are lower priority due to their potential for causing hypoglycemia. ACP says that sulfonylureas and long-acting insulin are “inferior to SGLT2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control.”
The two groups continue to differ regarding A1c goals, although both recommend individualization. The ACP generally advises levels between 7% and 8% for most adults with type 2 diabetes, and de-intensification of pharmacologic agents for those with A1c levels below 6.5%. On the other hand, ADA recommends A1c levels < 7% as long as that can be achieved safely.
This is the first time ACP has addressed this topic in a guideline, panel chair Carolyn J. Crandall, MD, told Medscape Medical News. “Diabetes treatment, of course, is our bread and butter…but what we had done before was based on the need to identify a target, like glycosylated hemoglobin. What patients and physicians really want to know now is, who should receive these new drugs? Should they receive these new drugs? And what benefits do they have?”
Added Crandall, who is professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles, “At ACP we have a complicated process that I’m actually very proud of, where we’ve asked a lay public panel, as well at the members of our guideline committee, to rank what’s most important in terms of the health outcomes for this condition…And then we look at how to balance those risks and benefits to make the recommendations.”
In the same Annals of Internal Medicine issue are two systematic reviews/meta-analyses that informed the new document, one on drug effectiveness and the other on cost-effectiveness.
In the accompanying editorial from Fatima Z. Syed, MD, an internist and medical weight management specialist at Duke University Division of General Internal Medicine, Durham, North Carolina, she notes, “the potential added benefits of these newer medications, including weight loss and cardiovascular and renal benefits, motivate their prescription, but cost and prior authorization hurdles can bar their use.”
Syed cites as “missing” from the ACP guidelines an analysis of comorbidities, including obesity. The reason for that, according to the document, is that “weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis.”
However, Syed notes that factoring in weight loss could improve the cost-effectiveness of the newer medications. She points out that the ADA Standards suggest a GLP-1 agonist with or without metformin as initial therapy options for people with newly diagnosed type 2 diabetes who might benefit from weight loss.
“The ACP guidelines strengthen the case for metformin as first-line medication for diabetes when comorbid conditions are not present. Metformin is cost-effective and has excellent hemoglobin A1c reduction. The accompanying economic analysis tells us that in the absence of comorbidity, the newer medication classes do not seem to be cost-effective. However, given that many patients with type 2 diabetes have obesity or existing cardiovascular or renal disease, the choice and accessibility of newer medications can be nuanced. The cost-effectiveness of GLP1 agonists and SGLT2 inhibitors as initial diabetes therapy in the setting of various comorbid conditions warrants careful exploration.”
Crandall has no disclosures. Syed disclosed that her husband is employed by Blue Cross Blue Shield of North Carolina.
Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X (formerly Twitter) @MiriamETucker.