The American College of Physicians (ACP) released a new clinical guideline on April 19, 2024, for Newer Pharmacologic Treatments in Adults With Type 2 Diabetes. This guideline focused specifically on three classes of medications commonly used for patients with Type 2 Diabetes Mellitus:

  • Sodium–glucose cotransporter-2 inhibitor (SGLT-2)
  • Glucagon-like peptide-1 agonist (GLP-1)
  • dipeptidyl peptidase-4 inhibitor (DPP-4) 

While the guideline is relatively short, consisting of only three key recommendations, the impact of these recommendations is significant.

ACP strongly recommends both SGLT2s and GLP1s as additions to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control. This is very much consistent with other Type 2 Diabetes Mellitus Guidelines from organizations such as the American Association of Clinical Endocrinology (AACE), the American Diabetes Association (ADA), and many others. However, where ACP differs is that, with the 2024 diabetes guideline update, they now DO NOT recommend DPP4s as an addition to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control. This not only differs from other guidelines, such as those from AACE and ADA guidelines, which either recommend DPP4s as an alternative therapy, or stay neutral on DPP4s, but it also reverses course for ACP itself, since it’s previous 2017 Guidelines for Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus did include a moderate recommendation in favor of adding a DPP-4 inhibitor to metformin to improve glycemic control when a second oral therapy is considered.

ACP states that the reason for the change is the high-certainty evidence showed that add-on DPP-4 inhibitors, compared with usual care, result in no differences in all-cause mortality, MACE, MI, stroke, CHF hospitalization, CKD progression, or severe hypoglycemia. Furthermore, evidence suggests that DPP-4 inhibitors may increase risk of hospitalization due to CHF and probably increase the risk for MACE and progression of CKD. Low-certainty evidence from a cost-effectiveness analysis also suggested that DPP-4 inhibitors may be more expensive and less effective than alternatives.

We should see new guideline updates from AACE and ADA within the next 6 months or less, so it will be interesting to see if those organizations take a similar stance to ACP and remove their recommendations for DPP-4 inhibitors to improve glycemic control in patients with Type 2 Diabetes Mellitus.

What are your thoughts on the new ACP Diabetes Guidelines, and specifically, their decision to now recommend against DPP4s? And do you think other organizations will follow suit in future guidelines?

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