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Type 2 diabetes drugs vary in impact on survival

Overall mortality lower with SGLT-2 inhibitors and GLP-1 agonists than with DPP-4 inhibitors

Louise Prime

Wednesday, 18 April 2018

Not all drugs to treat type 2 diabetes are equal in terms of improving survival, a large meta-analysis has shown. The UK-based study,* published in JAMA, revealed that in patients with type 2 diabetes the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors or glucagon-like peptide 1 (GLP-1) agonists was associated with better mortality outcomes than dipeptidyl peptidase 4 (DPP-4) inhibitors.

The research team, led from Imperial College, London, undertook a network meta-analysis that included 236 trials – with a total of 176,310 participants – to compare the efficacies of SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on all-cause mortality. They also analysed secondary outcomes: cardiovascular (CV) mortality, heart failure (HF) events, myocardial infarction (MI), unstable angina, and stroke.

They reported that SGLT-2 inhibitors (hazard ratio, HR 0.80) and GLP-1 agonists (HR 0.88) were associated with significantly lower all-cause mortality than the control groups; and that SGLT-2 inhibitors (HR 0.78) and GLP-1 agonists (HR 0.86) were associated with lower mortality than were DPP-4 inhibitors. DPP-4 inhibitors were not significantly associated with lower all-cause mortality (HR 1.02) than were the control groups.

They also found that SGLT-2 inhibitors (HR 0.79) and GLP-1 agonists (HR 0.85) were significantly associated with lower CV mortality than were the control groups. SGLT-2 inhibitors were significantly associated with lower rates of HF events (HR 0.62) and MI (HR 0.86) than were the control groups.

However, GLP-1 agonists were associated with a higher risk of adverse events leading to trial withdrawal than were SGLT-2 inhibitors (HR 1.80) and DPP-4 inhibitors (HR 1.93).

The study authors noted that the SGLT-2 inhibitors were associated with additional cardiovascular benefits for heart failure events compared with incretin-based therapies and control groups, and for MI events compared with control groups. They suggested that of the three drug classes tested, SGLT-2 inhibitors might “be preferred over the incretin-based therapies based on their association with lower mortality and their favourable adverse event profile”.

They concluded: “In this network meta-analysis, the use of SGLT-2 inhibitors or GLP-1 agonists was associated with lower mortality than DPP-4 inhibitors or placebo or no treatment. Use of DPP-4 inhibitors was not associated with lower mortality than placebo or no treatment.”


* Zheng SL, Roddick AJ, Aghar-Jaffar R, et al. Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl deptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes: a systematic review and meta-analysis. JAMA 2018; 319(15): 1580–1591. doi:10.1001/jama.2018.3024.

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