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.

The analysis clarifies which treatments do not have an overall benefit on patient-oriented outcomes. The older treatments, including insulin, do not affect mortality or hospitalizations, and thiazolidinediones increase the likelihood of being admitted for heart failure. Metformin, the cornerstone of treatment in most guidelines, may not have a benefit over standard treatment.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Foundation

Setting: Various (meta-analysis)

Reference: Shi Q, Nong K, Vandvik PO, et al. Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials. BMJ. 2023;381:e074068.

Editor's Note: Dr. Shaughnessy is an assistant medical editor for AFP.