SGLT2 inhibitors, metformin tied to prolonged survival in type 2 diabetes compared to other drugs

These findings suggest using specific antidiabetic compounds as a preventative strategy to promote healthspan not only in patients with type 2 diabetes but also in middle-aged to elderly nonT2Ds. The study was published on medRxiv.com as a preprint and has yet to be peer-reviewed.

"Metformin treatment was significantly linked with reduced mortality in type 2 diabetes patients compared to treatment with other antidiabetes drug classes. Still, metformin failed to produce survival rates that matched people without diabetes," Elisa Araldi, Swiss Federal Institute of Technology (ETH) Zürich, Schwerzenbach, Switzerland, and colleagues reported.

Treatment with SGLT2 (sodium-glucose cotransporter) inhibitors was also significantly associated with increased survival compared to other glucose-lowering medications. Survival of type 2 diabetes on SGLT2i treatment approximated that of people without diabetes, and also the treatment was linked with significantly lower cancer-related mortality.

In a prospective population-based study, Araldi and the team investigated the mortality risk linked to prescribing different antidiabetic medication classes.

In the analyses, the authors included 410 389 of the 502 536 participants in the UK Biobank with covariate data, prescription and clinical records. Forty-three thousand six hundred ten were diagnosed with type 2 diabetes. A nearest neighbour covariate matching (NNCM) algorithm was applied to match cohorts of antidiabetic medication class users to minimally differing control cohorts diagnosed with type 2 diabetes or without.

The primary outcomes of the study were all-cause mortality and causes of death.

The authors reported the following findings:

• During a median of 12.2 years of follow-up, 3.3% of individuals died.
• After applying NNCM, participants with T2D on metformin (average hazard ratio 0.39) or SGLT2I (average hazard ratio 0.58) have an increased survival probability compared to matched individuals with T2D.
• Compared to matched individuals without T2D, the survival probability of individuals with T2D increases only if prescribed SGLT2I (average hazard ratio 0.31).
• NNCM-based analysis of matched individuals with T2D on both SGLT2I and metformin versus metformin only reveals increased survival in the presence of SGLT2I (average hazard ratio 0.29), also when compared to matched identical individuals without T2D (average hazard ratio 0.05).
• All the other antidiabetic drugs analyzed are either detrimental in prolonging lifespan (insulin, thiazolidinediones, and sulfonylureas) or have no effect (DPP4 inhibitors and GLP1 receptor agonists).

"Metformin and SGLT2i users had a considerable survival advantage compared to noT2D or metformin-only users compared to noT2D," the authors concluded.

Reference:

Effects of antidiabetic drugs on mortality risks in individuals with type 2 diabetes: A prospective cohort study of UK Biobank participants. Elisa Araldi, Catherine R. Jutzeler, Michael Ristow. medRxiv 2023.05.19.23290214; doi: https://doi.org/10.1101/2023.05.19.23290214