ACP's New Type 2 Diabetes Guidance Recommends SGLT2is, GLP-1 RAs as Second-Line to Metformin

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The American College of Physicians (ACP) has released updated clinical recommendations for adults with type 2 diabetes, with the organization now recommending use of SGLT2 inhibitors and GLP-1 receptor agonists as second-line options to metformin in light of the cardiovascular and renal protective benefits of these agents.

Announced on the opening day of the ACP Internal Medicine Meeting 2024, the new recommendations call for clinicians to consider use of SGLT2 inhibitors or GLP-1 receptor agonists as second-line therapy to metformin in adults with type 2 diabetes and inadequate glycemic control, with an additional recommendation to avoid adding a DPP-4 inhibitor to metformin as second-line therapy in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.¹

“As additional pharmacological treatments become available for the treatment of Type 2 diabetes, it’s critical for us to examine their effectiveness, the harms and benefits as well as costs in order to provide the best treatment for our patients,” said Carolyn J. Crandall, MD, MS, an internal medicine physician at the University of California Los Angeles School of Medicine and the chair of the Guidelines Committee.² “Adding a second medication to metformin for patients with inadequate glycemic control may provide additional benefits but the added benefit on important clinical outcomes may be minimal in relation to the high cost, particularly for the more expensive, newer medications.”

The first recommendation from the ACP outlines SGLT2 inhibitors and GLP-1 receptor agonist as second-line therapies to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control. This recommendation included the caveat that clinicians should consider an SGLT 2 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 and consider a GLP-1 receptor agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke. No such caveats were included with the second recommendation, which recommended against adding a DPP-4 inhibitor because the evidence review indicated this class did not reduce morbidity or all-cause mortality.¹

The basis of the recommendations made by the ACP in their latest update were based on the results of a comprehensive systematic review and network meta-analysis on the topic Conducted by Timothy Wilt, MD, MPH, and 10 colleagues, the systematic review and network meta-analysis sought to provide an overview of the effectiveness, comparative effectiveness, and harms of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and long-acting insulins as both monotherapies and as combination therapy in adults with type 2 diabetes mellitus³

Limiting their review to randomized controlled trials 52 weeks in length or greater published from 2010 through January 2023 with at least 500 adult participants with type 2 diabetes. A total of 130 publications from 84 randomized controlled trials were included. Of note, certainty of evidence (CoE) of these trials was assessed using the GRADE framework.³

When compared to usual care, results suggested SGLT2 inhibitors and GLP-1 receptor agonists reduce all-cause mortality (high CoE) and major adverse cardiovascular events (moderate to high CoE), SGLT2 inhibitors reduce progression of chronic kidney disease and heart failure hospitalizations and GLP-1 receptor agonists reduce stroke (high CoE), and SGLT2 inhibitors reduce serious adverse events and severe hypoglycemia (high CoE). An accompanying cost-effectiveness performed as part of the process for drafting these recommendations concluded GLP-1 receptor agonist and SGLT2 inhibitors were viewed as being of low value as first-line therapies but could provide intermediate value when added to metformin or other background as compared to adding nothing.^3,4

In their announcement of the new recommendations, the ACP underlined the guidance issue by the organization emphasize shared decision-making, recognizing that each patient's needs and circumstances are unique. Additionally, clinicians are encouraged to consider individual patient characteristics like age, comorbidities, and personal preferences when discussing a treatment plan for type 2 diabetes.²

“Primary care physicians provide care for more than 90% of patients with type 2 diabetes mellitus,” wrote Fatima Syez, MD, MSc, in an accompanying editorial.⁵ “Thus, it is essential that they are familiar with the clinical effectiveness and cost-effectiveness of the growing number of medications used to treat [type 2 diabetes mellitus].”

References:

1. Qaseem A, Obley AJ, Shamliyan T, Hicks LA, Harrod CS, Crandall CJ. Newer pharmacologic treatments in adults with type 2 diabetes: A clinical guideline from the American College of Physicians. Annals of Internal Medicine. Published online April 19, 2024. doi:10.7326/m23-2788
2. American College of Physicians. ACP issues clinical recommendations for newer pharmacological treatments of adults with type 2 diabetes. ACP issues clinical recommendations for newer pharmacological treatments of adults with Type 2 diabetes | ACP Online. April 19, 2024. Accessed April 19, 2024. https://www.acponline.org/acp-newsroom/acp-issues-clinical-recommendations-for-newer-pharmacological-treatments-of-adults-with-type-2.
3. Drake T, Landsteiner A, Langsetmo L, et al. Newer pharmacologic treatments in adults with type 2 diabetes: A systematic review and network meta-analysis for the American College of Physicians. Annals of Internal Medicine. Published online April 19, 2024. doi:10.7326/m23-1490
4. Schousboe JT, Landsteiner A, Drake T, et al. Cost-effectiveness of newer pharmacologic treatments in adults with type 2 diabetes: A systematic review of cost-effectiveness studies for the American College of Physicians. Annals of Internal Medicine. Published online April 19, 2024. doi:10.7326/m23-1492
5. Syed FZ. Pharmacologic Treatments in Adults With Type 2 Diabetes: Cost-Effectiveness and Comorbidity Considerations. Annals of Internal Medicine. Published online April 19, 2024. doi:10.7326/M24-0861