New living guideline offers advice on medications for type 2 diabetes

A new living clinical practice guideline on medications for adults with type 2 diabetes offers recommendations based primarily on patients' cardiovascular (CV) and renal risk, as well as individual context and shared decision making.

The guideline was developed by an international panel as part of the BMJ Rapid Recommendations series and was published by The BMJ on Aug. 14. It was based in part on a living systematic review and meta-analysis, also published Aug. 14 by The BMJ, which included randomized controlled trials published through July 31, 2024.

The panel noted that the guideline prioritizes medications' effects on CV and kidney complications rather than HbA1c levels and other indicators of glycemic control and also weighs patients' probable inclination to accept a particular therapy. Its risk-stratified recommendations cover sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, finerenone, and tirzepatide.

To determine individual patients' risk as it relates to the guideline, clinicians should consider whether they have established cardiovascular disease (CVD) or chronic kidney disease (CKD), the guideline panel said. Those who have neither should be classified based on their CV risk, with those who have three or fewer risk factors (excluding diabetes) considered at lower risk for CV and kidney complications and those who have more than three considered at moderate risk. Adults who do have established CVD or CKD are classified as being at moderate risk or higher risk of complications; adults with CKD may be classified based on estimated glomerular filtration rate and degree of albuminuria according to the KDIGO classification, the guideline panel said.

For patients in the lower-risk group, the guideline makes a weak recommendation against SGLT-2 inhibitors or GLP-1 receptor agonists. “Given little or no benefit (high certainty evidence), risk of harms (genital mycotic infections for SGLT-2 inhibitors and severe gastrointestinal events for GLP-1 receptor agonists, both informed by moderate certainty evidence), and treatment burdens, the majority of adults were anticipated to be disinclined to accept SGLT-2 inhibitors or GLP-1 receptor agonists,” the panel wrote. They also indicated, however, that some adults may choose treatment due to the potential CV and kidney benefits and the fact that harms are reversible.

For adults at moderate risk, the guideline makes a weak recommendation in favor of SGLT-2 inhibitors or GLP-1 receptor agonists. “The cumulative cardiovascular and kidney benefits across outcomes (moderate to high certainty evidence) likely outweigh the risk of harms,” the panel wrote. They noted that the choice of one class over another is contextual and likely to vary by individual patient preference. The guideline also offers a weak recommendation against finerenone in adults with CKD who are at moderate CV and renal risk.

For patients at higher risk for CV and renal complications, there is a strong recommendation in favor of SGLT-2 inhibitors or GLP-1 receptor agonists and a weak recommendation in favor of finerenone in adults with CKD. “Given the benefit on overall survival (high certainty evidence), important benefits on cardiovascular and kidney outcomes (moderate to high certainty evidence), and taking into account risk of harms (moderate certainty evidence) and treatment burdens, all or almost all higher risk patients with established disease were anticipated to be inclined to accept treatment; this justified a strong recommendation in favour,” the authors wrote. “The panel also considered high certainty evidence of important benefits associated with SGLT-2 inhibitors for patients with established heart failure irrespective of diabetes status and agreed a strong recommendation in favour was in keeping with these established benefits.”

The guideline also offered a weak recommendation in favor of tirzepatide in adults with obesity across all risk levels, noting that the drug should not be given in combination with GLP-1 receptor agonists but can be combined with SGLT-2 inhibitors and finerenone. “In adults at higher risk of cardiovascular and kidney complications, tirzepatide should generally not replace medications effective in reducing the risk of these complications,” the panel wrote. “If replacing a GLP-1 receptor agonist with tirzepatide, initiation or continuation of an SGLT-2 inhibitor is indicated.”

An accompanying editorial said that while the guidance prioritizes reduction of CV and renal complications, HbA1c levels remain a valuable measure and glycemia should continue to be managed in parallel with CV and renal risk. “Overall, the new recommendations may be most applicable to patients with HbA1c values between 6.5% (48 mmol/mol) and 8% (64 mmol/mol), in line with the evidence base supporting these guideline interventions,” the editorialist wrote. He noted that future guidelines could be further refined by assigning weightings to specific comorbid conditions, such as CVD, CKD, and obesity, and by accounting for characteristics such as gender, duration of diabetes, and baseline HbA1c level.