A review of the effects of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors on lean body mass in humans

Weight loss is an important goal in the management of several chronic conditions, including type 2 diabetes mellitus, and pharmacological therapies that aid weight loss are appealing. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) are novel glucose-lowering therapies that have been shown to induce clinically significant reductions in body weight. However, this weight loss may not be attributed solely to fat mass (FM). Given the importance of skeletal muscle and lean body mass (LBM) on cardio-metabolic health and physical function, we reviewed the available literature reporting the effects of GLP-1RAs and SGLT2is on body composition. Results demonstrate that, in most circumstances, the weight loss associated with both therapies predominantly comprises a reduction in FM, although significant heterogeneity exists between studies. In over half of the studies identified, the proportion of LBM reduction ranged between 20% and 50% of total weight lost, which is consistent with diet-induced weight loss and bariatric surgery. No clear differences existed between GLP-1RAs and SGLT2is. Consequently, the loss of LBM and skeletal muscle associated with weight loss induced by GLP-1RAs and SGLT2is warrants attention. Strategies to preserve skeletal muscle and improve physical function, for example through structured exercise, are of great importance

Influence of hyper-energetic, high-fat feeding on circulating hepatokines in healthy men: a randomised crossover study [Abstract]

No description supplie

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

The role of hepatic lipid composition in obesity-related metabolic disease

Obesity is a primary antecedent to non-alcoholic fatty liver disease whose cardinal feature is excessive hepatic lipid accumulation. Although total hepatic lipid content closely associates with hepatic and systemic metabolic dysfunction, accumulating evidence suggests that the composition of hepatic lipids may be more discriminatory. This review summarises cross-sectional human studies using liver biopsy/lipidomics and proton magnetic resonance spectroscopy to characterise hepatic lipid composition in people with obesity and related metabolic disease. A comprehensive literature search identified 26 relevant studies published up to 31st March 2021 which were included in the review. The available evidence provides a consistent picture showing that people with hepatic steatosis possess elevated saturated and/or monounsaturated hepatic lipids and a reduced proportion of polyunsaturated hepatic lipids. This altered hepatic lipid profile associates more directly with metabolic derangements, such as insulin resistance, and may be exacerbated in non-alcoholic steatohepatitis. Further evidence from lipidomic studies suggests that these deleterious changes may be related to defects in lipid desaturation and elongation, and an augmentation of the de novo lipogenic pathway. These observations are consistent with mechanistic studies implicating saturated fatty acids and associated bioactive lipid intermediates (ceramides, lysophosphatidylcholines and diacylglycerol) in the development of hepatic lipotoxicity and wider metabolic dysfunction, whilst monounsaturated fatty acids and polyunsaturated fatty acids may exhibit a protective role. Future studies are needed to prospectively determine the relevance of hepatic lipid composition for hepatic and non-hepatic morbidity and mortality; and to further evaluate the impact of therapeutic interventions such as pharmacotherapy and lifestyle interventions

The effect of exercise training on adipose tissue insulin sensitivity: a systematic review and meta-analysis [Abstract]

The effect of exercise training on adipose tissue insulin sensitivity: a systematic review and meta-analysis [Abstract]</p

Preservation of healthy lean body mass and function during weight loss

Sustainable treatments for obesity are needed and novel pharmacotherapies that aid weight loss appear promising. In their proposed agenda, Pinkney and Tarrant1 highlight additional priorities towards behavioural approaches in people living with obesity alongside current and emerging medical treatment. We support these suggestions and would like to highlight a different but aligned area of importance: the preservation of healthy lean body mass (LBM), in particular, skeletal muscle and physical function, during periods of substantial weight loss. [...]</p

Preservation of healthy lean body mass and function during weight loss

Sustainable treatments for obesity are needed and novel pharmacotherapies that aid weight loss appear promising. In their proposed agenda, Pinkney and Tarrant1 highlight additional priorities towards behavioural approaches in people living with obesity alongside current and emerging medical treatment. We support these suggestions and would like to highlight a different but aligned area of importance: the preservation of healthy lean body mass (LBM), in particular, skeletal muscle and physical function, during periods of substantial weight loss.</p

The effect of exercise training on adipose tissue insulin sensitivity: A systematic review and meta-analysis

This systematic review and meta-analysis determined the impact of exercise training on adipose tissue insulin sensitivity in adults. Its scope extended to studies measuring whole-body and localised subcutaneous adipose tissue insulin sensitivity using validated techniques. Consensus from four studies demonstrates that exercise training improved whole-body adipose tissue insulin sensitivity when measured via stable-isotope lipid tracers (rate of appearance suppression in response to hyperinsulinaemia). Meta-analysis of 20 studies (26 intervention arms) employing the adipose tissue insulin resistance index (ADIPO-IR) supported these findings (-10.63 [-14.12 to – 7.15] pmol.L-1 x mmol.L-1). With ADIPO-IR, this response was greater in studies documenting weight loss and shorter sampling time (≤ 48 h) post-training. Overall, exercise training did not affect whole-body adipose tissue insulin sensitivity in 7 studies (11 intervention arms) measuring the suppression of circulating non-esterified fatty acid in response to insulin infusion (1.51 [-0.12 to – 3.14] %); however, sub-group analysis identified an enhanced suppression post-training in trials reporting weight loss. From four microdialysis studies, consensus indicates no effect of exercise training on localised (abdominal/femoral) adipose tissue insulin sensitivity; potentially suggesting that enhanced whole-body responses are related to improvements in central adipose depots. However, heterogeneity within microdialysis protocols dictates that findings must be viewed with caution

The hepatokine leukocyte cell-derived chemotaxin-2 is elevated in people with impaired glycaemic control and augmented by acute exercise [Abstract]

Conference abstract presented at EASL SLD (Steatotic Liver Disease) Summit 2023.</p