Metformin, SGLT2is Link With Longer T2D Survival

Miriam E. Tucker, for Medscape

June 12, 2023

The study covered in this summary was published on as a preprint and has not yet been peer reviewed.

Key Takeaways

  • Treatment with metformin significantly linked with reduced mortality in people with type 2 diabetes compared with treatment with other antidiabetes drug classes, but metformin did not produce survival rates that matched people without diabetes.

  • Treatment with a sodium-glucose cotransporter 2 inhibitor (SGLT2i) also significantly associated with increased longevity compared with treatment with other glucose-lowering medications. Survival of people with type 2 diabetes on SGLT2i treatment approximated that of people without diabetes, and SGLT2i treatment also linked with significantly lower cancer-related mortality.

Why This Matters

  • Previous studies had limited follow-up duration, small sample sizes, excluded people with preexisting malignancies, and didn't compare survival with matched individuals without type 2 diabetes.

  • Assessing changes in survival linked with various glucose-lowering medications can guide selection of second-line agents.

  • The results should encourage clinicians to consider metformin and an SGLT2i agent for either single- or dual-drug first-line treatment of people with type 2 diabetes.

Study Design

  • Prospective population-based study of 410,389 UK Biobank adults enrolled during 2006–2010, including 43,610 diagnosed with type 2 diabetes at entry.

  • Among those with type 2 diabetes, 57% were taking metformin, 21% insulin, 16% a sulfonylurea, 14% a dipeptidyl peptidase 4 inhibitor (DPP4i), 8% an SGLT2i, and 4.2% a glucagon-like peptide-1 receptor agonist (GLP-1RA). Fewer than 2% were taking other agents.

  • A third of the people with type 2 diabetes included in the review received monotherapy, and 31% were not taking any antidiabetes medication.

  • The researchers used a nearest-neighbor covariate matching strategy. They individually matched each person who had type 2 diabetes and were prescribed the drug of interest with either someone with type 2 diabetes but who were not prescribed the drug of interest or with someone without type 2 diabetes, with matching depending on covariate similarities.

Key Results

  • Over a median 12 years' follow-up, mortality rates were highest among those using sulfonylureas, at 7.6%, and insulin, at about 10%. The lowest mortality rates were among those on an SGLT2i or a GLP-1 RA.

  • In the nearest-neighbor covariate matching analyses of people with type 2 diabetes, only metformin, with a hazard ratio of 0.40, and SGLT2is, with a hazard ratio of 0.47, linked with significantly reduced all-cause mortality compared with people who received other agents.

  • People who were treated with a sulfonylurea or with insulin had significantly higher mortality compared with those using other agents in nearest-neighbor covariate matching analyses.

  • Compared with matched individuals without type 2 diabetes, only SGLT2is conferred a consistent survival advantage, significantly linking with a 69% reduction relative to matched individuals. Treatment with a DPP4i showed a significant survival advantage in Cox proportional multivariate hazard analysis but not in Kaplan-Meier estimates, and metformin did not improve survival in people with type 2 diabetes compared with matched participants without type 2 diabetes.

  • Those using both an SGLT2i and metformin had a significant survival advantage over those treated with metformin alone and when compared with matched individuals without type 2 diabetes.


  • Differences in bioavailability, target affinity, and off-target effects of individual compounds in the same drug class might influence long-term outcomes, and the effect of an individual drug within each of the studied drug classes may be lost or overstated when analyzed in combination with other medications in that drug class.

  • People in the study had relatively short exposure times to agents from certain classes that have been more recently introduced, specifically the SGLT2is, the GLP-1 RAs, and the DPP4is.

  • The data analyses relied on patient characteristics quantified at the time of entry into the UK Biobank database and so and do not fully reflect clinical events, nor changes in physical and lifestyle characteristics throughout the observation period.


  • The study received no commercial funding.

  • None of the authors had disclosures.

This is a summary of a preprint research study, "Effects of Antidiabetic Drugs on Mortality Risks in Individuals With Type 2 Diabetes: A Prospective Cohort Study of UK Biobank Participants," by researchers from the Swiss Federal Institute of Technology, Zürich, Switzerland, on medRxiv and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on

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