Type 2 Diabetes and Impaired Physical Function: A Growing Problem

The focus in diabetes care has traditionally been around the optimisation of the glycaemic control and prevention of complications. However, the prevention of frailty and improvement in physical function have now emerged as new targets of diabetes management. This is mainly driven by the significant adverse impact that early onset frailty and decline in physical function have on health outcomes, functional independence, and quality of life in people with type 2 diabetes (T2D). There is an increasing emphasis in the expert consensus and management algorithms to improve physical function in people with T2D, predominantly through lifestyle interventions, including exercise and the control of modifiable risk factors. Trials of novel glucose-lowering therapies (GLTs) also now regularly assess the impact of these novel agents on measures of physical function within their secondary outcomes to understand the impact that these agents have on physical function. However, challenges remain as there is no consensus on the best method of assessing physical function in clinical practice, and the recognition of impaired physical function remains low. In this review, we present the burden of a reduced physical function in people with T2D, outline methods of assessment used in healthcare and research settings, and discuss strategies for improvement in physical function in people with T2D

Exercise, pharmaceutical therapies and type 2 diabetes: looking beyond glycemic control to whole body health and function

Exercise is a powerful therapy for improving glycemic control and increasing cardiorespiratory fitness in adults with type 2 diabetes mellitus (T2DM). However, there is a dearth of evidence investigating interactions or synergies between exercise and most pharmaceutical therapies. This is important as exercise is rarely prescribed in isolation of other background medications used to manage T2DM. Therefore understanding which exercise and drug combinations optimize or blunt responses is crucial. This narrative review discusses advances in weight loss management in diabetes and highlights research opportunities and challenges for combining exercise therapies with newer generations of glucose-lowering therapies with weight loss effects, particularly glucagon- like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is). We discuss the role of exercise in preserving lean mass and increasing physical function along with other potential areas of synergy. We conclude that until the evidence base investigating areas of interaction or synergy between exercise and other glucose-lowering or weight loss therapies is developed, exercise will remain a generic rather than a tailored therapy in the management of T2DM

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.</p

Initiation of new glucose-lowering therapies may act to reduce physical activity levels: pooled analysis from three randomized trials

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown. RESEARCH DESIGN AND METHODS. We pooled data (n = 148) from three randomised trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison to sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies on accelerometer-assessed physical activity. RESULTS: Liraglutide (-1144 steps/day; 95% CI -2069, -220), empagliflozin (-1132 steps/day; -1739, -524) and sitagliptin (-852 steps/day; -1625, -78) resulted in reduced total daily physical activity after 6 months (p CONCLUSIONS: The initiation of all glucose lowering therapies was associated with reduced physical activity, warranting further investigation.</p

Initiation of New Glucose-Lowering Therapies May Act to Reduce Physical Activity Levels: Pooled Analysis From Three Randomized Trials.

ObjectiveSodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown.Research design and methodsWe pooled data (n = 148) from three randomized trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison with sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies, on accelerometer-assessed physical activity.ResultsLiraglutide (mean -1,144 steps/day; 95% CI -2,069 to -220), empagliflozin (-1,132 steps/day; -1,739, -524), and sitagliptin (-852 steps/day; -1,625, -78) resulted in reduced total daily physical activity after 6 months (P ConclusionsThe initiation of all glucose-lowering therapies was associated with reduced physical activity, warranting further investigation