Clinical Question

What treatments for type 2 diabetes mellitus decrease the likelihood of patient-oriented outcomes?

Bottom Line

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists reduce all-cause and cardiovascular mortality and other cardiac-related problems. Older treatments, including insulin, do not affect long-term outcomes. Metformin was not found to be more effective than standard treatment to prevent important outcomes, which is consistent with previous findings and may cause it to be removed as a cornerstone of treatment. (Level of Evidence = 1a−)

Synopsis

The investigators searched three databases, including Cochrane Central, and identified 816 English-language randomized controlled studies (N = 471,038) that compared two or more medications for type 2 diabetes. The researchers followed PRISMA criteria for reporting. Approximately one-fourth of the studies had a high risk of bias, usually from lack of masking (62%). The researchers conducted a network meta-analysis and compared all medications with one another by combining direct and indirect evidence across the studies. All the studies were short-term, with a median duration of six months. SGLT-2 inhibitors and GLP-1 receptor agonists reduced all-cause mortality to a small extent compared with usual treatment. They also reduced death due to cardiovascular causes, the likelihood of nonfatal myocardial infarction, and admission for heart failure. They have shown similar rates of adverse effects compared with usual care. Finerenone (Kerendia) probably reduces admissions for heart failure and end-stage kidney disease compared with usual care. Tirzepatide (Mounjaro) is associated with the greatest amount of weight loss.