Updated guideline reflects new medications for type 2 diabetes

Updated guideline reflects new medications for type 2 diabetes

Type 2 diabetes (T2D) is the most common form of diabetes, accounting for more than 90% of all cases worldwide. The prevalence of T2D is increasing worldwide, mainly due to behavioral and social factors related to obesity, diet and physical activity. The International Diabetes Federation estimated in its 2021 report that 537 million adults between the ages of 20 and 79 have been diagnosed with diabetes worldwide. The organization predicts an increase to 643 million in 2030 and 743 million in 2045.

The most important therapeutic goals for patients with type 2 diabetes are adequate glycemic control and primary and secondary prevention of atherosclerotic cardiovascular and renal diseases, which account for almost half of all deaths among adults with type 2 diabetes. Despite the many treatment options available, 16% of adults with T2D have inadequate glycemic control, including A1c levels > 9%, even though glycemic control was the focus of the 2017 American College of Physicians (ACP) guidelines.

Therefore, the ACS deemed it necessary to update the previous guidelines, taking into account new evidence on the efficacy and harms of new pharmacological treatments in adults with type 2 diabetes, with the aim of reducing the risk of all-cause, cardiovascular and cardiovascular mortality. morbidity and progression of chronic kidney disease. disease (CKD) in these patients.

New medicines

The pharmacologic treatments that the ACS considered in updating its guidelines include glucagon-like peptide 1 (GLP-1) receptor agonists (i.e., dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide), a GLP-1 receptor agonist, and a glucose dependent agonist. Insulinotropic polypeptide receptor agonist (i.e., tirzepatide), sodium glucose cotransporter 2 (SGLT-2) inhibitors (i.e., canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), dipeptidyl peptidase 4 (DPP-4) inhibitors (i.e., alogliptin, linagliptin, saxagliptin, and sitagliptin), and long-acting insulins (i.e. insulin glargine and insulin degludec).


The ACP recommends adding an SGLT-2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with inadequately controlled T2D (strong recommendation, high certainty of evidence). Use an SGLT-2 inhibitor to reduce the risk of all-cause mortality, major cardiovascular events (MACE), progression of chronic kidney disease, and hospitalization due to congestive heart failure, the document says. Use a GLP-1 agonist to reduce the risk of all-cause mortality, MACE, and stroke.

SGLT-2 inhibitors and GLP-1 agonists are the only newer pharmacological treatments for T2D that have reduced all-cause mortality beyond placebo or usual care. In indirect comparison, SGLT-2 inhibitors are likely to reduce the risk of hospitalization due to heart failure, while GLP-1 agonists are likely to reduce the risk of stroke.

Neither class of drugs causes severe hypoglycemia, but both are associated with different types of harm, as noted in specific warnings. Both classes of drugs lead to weight loss.

Compared with long-acting insulins, SGLT-2 inhibitors may reduce all-cause mortality, and GLP-1 agonists probably do. Compared with DPP-4 inhibitors, GLP-1 agonists likely reduce all-cause mortality.

Compared to DPP-4 inhibitors, SGLT-2 inhibitors are likely to reduce MACE, as well as compared to sulfonylureas.

The ACP recommends not adding a DPP-4 inhibitor to metformin and lifestyle changes in adults with inadequately controlled T2D to reduce all-cause morbidity and mortality (strong recommendation, high certainty of evidence).

Compared with usual therapy, DPP-4 inhibitors do not result in differences in all-cause mortality, MACE, myocardial infarction, stroke, hospitalization for chronic heart failure (CHF), progression of CKD, or severe hypoglycemia. Compared with SGLT-2 inhibitors, DPP-4 inhibitors may increase hospitalization due to CHF and likely increase the risk of MACE and CKD progression. Compared with GLP-1 agonists, they likely increase all-cause mortality and hospitalization due to CHF and the risk of MACE. Metformin is the most common usual therapy in the studies reviewed.

Considerations for practice

Metformin (unless contraindicated) and lifestyle changes are the first step in the treatment of T2D in most patients, according to the ACP.

The choice of adjunctive therapy requires a risk-benefit assessment and should be personalized based on patient preferences, glycemic control goals, comorbidities, and risk of hypoglycemia. According to the ACP, SGLT-2 inhibitors can be added in patients with T2D and CHF or CKD. GLP-1 agonists may be added in patients with T2D at increased risk of stroke or for whom total weight loss is an important therapeutic goal.

The A1c target should be considered between 7% and 8% in most adults with type 2 diabetes, and de-escalation of pharmacological treatments should be considered for A1c levels < 6.5%. According to the ACP, self-monitoring of blood glucose may not be necessary in patients treated with metformin in combination with an SGLT-2 inhibitor or a GLP-1 agonist.

The document also states that in cases of adequate glycemic control with the addition of an SGLT-2 inhibitor or a GLP-1 agonist, existing treatment with sulfonylureas or long-acting insulin should be reduced or discontinued due to the increased risk of severe hypoglycemia.

This story has been translated from Univadis Italy, which is part of the Medscape professional network, and uses several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.