Impact of novel glucose-lowering therapies on physical function in people with type 2 diabetes: A systematic review and meta-analysis of randomised placebo-controlled trials.

AIMS: We investigated evidence from randomised, placebo-controlled trials of novel glucose-lowering therapies; sodium-glucose co-transporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), on physical function in people with type 2 diabetes (T2D). METHODS: PubMed, Medline, Embase and Cochrane library were searched from 1 April 2005 to 20 January 2022. The primary outcome was change in physical function in groups receiving a novel glucose-lowering therapy versus placebo at the trial end-point. RESULTS: Eleven studies met our criteria including nine for GLP-1RA and one each for SGLT2i and DPP4i. Eight studies included a self-reported measure of physical function, seven with GLP-1RA. Pooled meta-analysis showed an improvement of 0.12 (0.07, 017) points in favour of novel glucose-lowering therapies, mainly GLP-1RA. These findings were consistent when assessed individually for commonly used subjective assessments of physical function; namely the Short-Form 36 item-questionnaire (SF-36; all investigating GLP-1RA) and the Impact of Weight on Quality of Life-Lite (IWQOL-LITE; all, except one, exploring GLP-1RA) with estimated treatment differences (ETDs) of 0.86 (0.28, 1.45) and 3.72 (2.30, 5.15) respectively in favour of novel GLTs. For objective measures of physical function (VO2max and 6-minute walk test (6MWT)) no significant between-group differences between the intervention and the placebo were found. CONCLUSIONS: GLP-1RAs showed improvements in self-reported outcomes of physical function. However, there is limited evidence to draw definitive conclusions especially because of lack of studies exploring the impact of SGLT2i and DPP4i on physical function. There is a need for dedicated trials to establish the association between novel agents and physical function.

The effects of weight-lowering pharmacotherapies on physical activity, function and fitness: A systematic review and meta-analysis of randomized controlled trials.

Weight-lowering pharmacotherapies provide an option for weight management; however, their effects on physical activity, function, and cardiorespiratory fitness are not fully understood. We conducted a systematic review and meta-analysis of randomized controlled trials to investigate the effect of licensed weight loss pharmacotherapies on physical activity, physical function, and cardiorespiratory fitness in individuals with obesity. Fourteen trials met our prespecified inclusion criteria: Five investigated liraglutide, four semaglutide, three naltrexone/bupropion, and two phentermine/topiramate. All 14 trials included a self-reported measure of physical function, with the pooled findings suggesting an improvement favoring the pharmacotherapy intervention groups (SMD: 0.27; 95% CI: 0.22 to 0.32) and effects generally consistent across different therapies. Results were also consistent when stratified by the two most commonly used measures: The Short-Form 36-Item Questionnaire (SF-36) (0.24; 0.17 to 0.32) and the Impact of Weight on Quality Of Life-Lite (IWQOL-Lite) (0.29; 0.23 to 0.35). Meta-regression confirmed a significant association between pharmacotherapy induced weight loss and improved physical function for IWQOL-Lite (p = 0.003). None of the studies reported a physical activity outcome, and only one study reported objectively measured cardiorespiratory fitness. Improvements in self-reported physical function were observed with weight loss therapy, but the effect on physical activity or objectively measured physical function and fitness could not be determined.