Age differences in efficacy of newer glucose lowering treatments for type 2 diabetes

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P Hanlon E Butterly L Wei H Wightman S Ali M Almazam K Alsallumi J Crowther R McChrystal H Rennison K Hughes J Lewsey R Lindsay S McGurnaghan J Petrie L A Tomlinson S Wild A Adler N Sattar D Phillippo S Diaz N Welton D McAllister
University of Glasgow, University of Oxford, University of York, University of Bristol, University of Edinburgh, London School of Hygiene and Tropical Medicine
Diabetes

Abstract

Background: Newer glucose-lowering agents for type 2 diabetes (sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor analogues (GLP1ra) and dipeptidyl peptidase-4 inhibitors (DPP4i)) improve hyperglycaemia and SGLT2i and GLP1ra reduce the risk of major adverse cardiovascular events (MACE). It is not clear whether the efficacy of these agents varies by age.

Methods: We searched Medline and Embase, plus clinical trial registries, for randomised controlled trials of SGLT2i, GLP1ra and DPP4i, versus placebo or active comparator, in adults with type 2 diabetes.

Outcomes: HbA1c and MACE. Where IPD were available, we modelled age-treatment interactions for each trial. Otherwise, we assessed age distributions along with results from aggregate trial data. IPD and aggregate findings were combined in a Bayesian network meta-analysis to assess whether the efficacy differed by age.

Results: We identified 616 eligible trials (604 reporting HbA1c, 23 reporting MACE) and obtained IPD for 75 trials (6 reporting MACE). Mean age was 59.0 (10.7) years and 64.0 (8.6) in HbA1c and MACE trials, respectively. SGLT2i reduced HbA1c by 0.5-1.0% overall compared to placebo. This reduction versus placebo was attenuated in older participants (change in HbA1c 0.25 percentage-points less for 75-year-olds compared to 45-year-olds). SGLT2i showed greater relative efficacy in MACE risk reduction among older than younger people. This finding was sensitive to the exclusion of one of the IPD MACE trials, however, in all sensitivity analyses, SGLT2i were either as efficacious or more efficacious in older participants. There was no consistent difference in efficacy by age for GLP1ra or DPP4i for HbA1c or MACE.

Conclusion: Newer glucose-lowering drugs are efficacious across age and sex groups. SGLT2i are more cardioprotective in older than younger people despite smaller HbA1c reductions. Age alone should not be a barrier to treatments with proven cardiovascular benefit providing they are well tolerated align with patient priorities.