Choice of SGLT-2 inhibitors, GLP-1 receptor agonists should be based on individual risk

A meta-analysis comparing sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists found differing effects, including that the SGLT-2 inhibitors affected heart failure outcomes while GLP-1 receptor agonists reduced stroke risk.


The effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists on cardiovascular and renal outcomes in type 2 diabetes vary based on patients' baseline risk, according to a new study.

As part of the BMJ Rapid Recommendations project, researchers performed a network meta-analysis of randomized controlled trials that compared SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose-lowering treatment in adult patients with type 2 diabetes and followed them for at least 24 weeks. The main outcome measures were estimated absolute effects of treatment per 1,000 patients treated for five years who were at very low risk (no cardiovascular risk factors), low risk (≥3 cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided critical oversight of the review. The results were published Jan. 13 by The BMJ.

Overall, 764 trials that included 421,346 patients were eligible for the meta-analysis. SGLT-2 inhibitors and GLP-1 receptor agonists were added to existing diabetes treatment in all cases. High-certainty evidence indicated that both drug classes lowered rates of all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction, and kidney failure. SGLT-2 inhibitors had a greater effect on mortality and hospital admission for heart failure than GLP-1 receptor agonists, while GLP-1 receptor agonists reduced nonfatal stroke and SGLT-2 inhibitors appeared to have no effect on this outcome. High-certainty evidence indicated that SGLT-2 inhibitors cause genital infection, and low-certainty evidence indicated that GLP-1 receptor agonists may cause severe gastrointestinal events. Low-certainty evidence suggested that both drug classes might decrease body weight. The researchers found little or no evidence regarding the effect of either drug class on limb amputation, blindness, eye disease, neuropathic pain, or health-related quality of life. The absolute benefits of the drug classes were found to vary widely by patients' risk for cardiovascular and renal outcomes.

The clinical settings of the included trials were heterogeneous, and some of the outcomes involved imprecise estimates of effects and low-quality evidence, the authors noted. They concluded that both SGLT-2 inhibitors and GLP-1 receptor agonists reduce cardiovascular and renal outcomes in adults with type 2 diabetes but that benefits and harms differ according to patients' individual level of risk. “Accordingly, the associated BMJ Rapid Recommendations will provide risk stratified recommendations and highlight the need for shared decision making to allow patients and clinicians to make well informed decisions together,” the authors wrote. The BMJ Rapid Recommendations on this topic are upcoming and will be published online.