Effects of novel glucose-lowering therapies on physical function

Frailty and impaired physical function are viewed as one of the major categories of complications associated with diabetes, with up to a five-fold increased risk of frailty in people with diabetes compared to the general population (Hanlon et al, 2018). The present systematic review and meta-analysis sought to assess the effects of novel glucose-lowering drugs (DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors) on physical function in people with type 2 diabetes.

A total of eleven phase 3 or phase 4 randomised controlled trials, with data on 6886 individuals with type 2 diabetes (3860 receiving the study drug and 3026 receiving placebo), were included in the analysis. Most participants (80%) were of white ethnicity and the weighted mean age was 61 years and the mean diabetes duration 12 years. Most studies reported on use of GLP-1 RAs, and mean follow-up was around 40 weeks.

Self-reported physical function outcomes using validated questionnaires were evaluated in seven studies; meta-analysis revealed significant improvements in both Short-Form 36 (estimated treatment difference [ETD], 0.86) and Impact of Weight on Quality of Life-Lite scores (ETD, 3.72). These were driven by GLP-1 RAs but not SGLT2 inhibitors or DPP-4 inhibitors.

Objective measures of physical function, including VO_2max and 6-minute walk tests, were evaluated in four studies. No significant improvements were found with any of the study drugs; however, sample sizes were small and the duration of follow-up was short.

The authors note that the self-report tools assess multiple domains of daily living, not all of which necessarily reflect physical function, so caution is needed when interpreting the results. They also highlight a high degree of heterogeneity between the studies. Nonetheless, the findings suggest a potential beneficial impact of GLP-1 RAs on improving physical function in people with type 2 diabetes, possibly associated with weight loss.

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