The following are key points to remember about a clinical guideline from the American College of Physicians (ACP) on newer pharmacologic treatments in adults with type 2 diabetes:

1. Type 2 diabetes is associated with higher risk for mortality and morbidity, greater health care use, and greater costs when adults with diabetes are compared with those without diabetes.
2. Major treatment goals for patients with type 2 diabetes include adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and kidney diseases, which account for nearly one half of all deaths among adults with type 2 diabetes.
3. This guideline addresses effectiveness and harms of newer pharmacologic treatments to reduce the risk for all-cause mortality, cardiovascular morbidity, and progression of chronic kidney disease (CKD) in adults with type 2 diabetes.
4. Newer pharmacologic treatments include glucagon-like peptide-1 (GLP-1) agonists (dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist (tirzepatide), sodium–glucose cotransporter-2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase-4 (DPP-4) inhibitors (alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (insulin glargine and insulin degludec).
5. The ACP recommends adding an SGLT-2 inhibitor or GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control (strong recommendation; high-certainty evidence).
6. The only newer pharmacologic treatments of type 2 diabetes that reduced all-cause mortality compared with placebo or usual care were SGLT-2 inhibitors and GLP-1 agonists.
   • Use of an SGLT-2 inhibitor is recommended to reduce the risk for all-cause mortality, major adverse cardiovascular events (MACE), progression of CKD, and hospitalization due to congestive heart failure [CHF]. Clinicians should prioritize adding SGLT-2 inhibitors in patients with type 2 diabetes and CHF or CKD.
   • Use of a GLP-1 agonist is recommended to reduce the risk for all-cause mortality, MACE, and stroke. Clinicians should prioritize adding GLP-1 agonists in patients with type 2 diabetes and an increased risk for stroke or for whom total body weight loss is an important treatment goal.
7. The ACP recommends against adding a dipeptidyl peptidase-4 (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 (strong recommendation; high-certainty evidence).
8. Metformin (unless contraindicated) and lifestyle modifications are the first steps in managing type 2 diabetes in most patients. When selecting an additional therapy, clinicians should consider the evidence of benefits, harms, patient burden, and cost of medications in addition to performing an individualized assessment of each patient’s preferences, glycemic control target, comorbid conditions, and risk for symptomatic hypoglycemia.
9. Overall, clinicians should aim to achieve glycated hemoglobin (HbA_1c) levels between 7% and 8% in most adults with type 2 diabetes and deintensify pharmacologic treatments in adults with HbA_1c levels <6.5%. An individualized glycemic goal should be based on risk for hypoglycemia, life expectancy, diabetes duration, established vascular complications, major comorbidities, patient preferences and access to resources, capacity for adequate monitoring of hypoglycemia, and other harms.
10. Finally, type 2 diabetes management should be based on collaborative communication and goal setting among all team members, including clinical pharmacists, to reduce the risk for polypharmacy and associated harms.

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention

Keywords: Diabetes Mellitus, Type 2, Pharmaceutical Preparations

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