Effect of SGLT2i & GLP-1 medications on Skeletal Muscle Health: A Scoping Review (Search Protocol)

In 2021, it was estimated that 537 million people were living with Type 2 Diabetes Mellitus (T2DM), a disease responsible for one death globally every five seconds (Federation, 2021). In addition, more than 10% of the global population has chronic kidney disease (CKD) (Kovesdy, 2022) while heart failure affects up to 67 million people (Yan et al., 2023). Alongside lifestyle modifications such as dietary and exercise interventions, pharmacological therapies are also available for the treatment of these conditions.  

Recently, Sodium-Glucose Transporter 2 Inhibitors (SGLT2i’s) and Glucagon-like Peptide 1 Receptor Agonists (GLP-1’s) have gained favour for the treatment of T2DM thanks to their robust impact on hyperglycaemia and bodyweight (Sargeant et al., 2019). In addition to the glycaemic benefits arising from both medications, large scale clinical trials investigating SGLT2i’s have observed improved renal and cardiovascular outcomes (Bernard Zinman et al., 2015, Neal et al., 2017). As a result, some SGLT2i’s are now approved for the treatment of both CKD and Heart Failure in individuals with or without T2DM (Administration, 2021, Administration, 2020).  

Both therapies target diverse physiological mechanisms, with SGLT2i’s inhibiting renal glucose reabsorption causing glycosuria, while GLP-1’s stimulate insulin production, suppress glucagon excretion and slow gastric emptying to promote satiety. Therefore, both classes of medication lead to reductions in body mass of 1-5kg (Sargeant et al., 2019). GLP-1’s impact on bodyweight is so significant that it is approved for the treatment of obesity in both the United Kingdom and United States. 

As with any weight loss intervention, reductions in fat mass are often accompanied with a reduction in skeletal muscle mass. ‘Sarcopenia’ is defined by the European Working Group on Sarcopenia in Older People (EWGSOP) as low muscle strength, quantity or quality (Cruz-Jentoft et al., 2019). The lack of globally accepted criteria and definitions for sarcopenia mean prevalence is difficult to accurately establish. However, meta-analyses have shown that globally, 10% of community-dwelling participants aged 60 years and older have sarcopenia (Yuan and Larsson, 2023). Rates appear higher among those with a long-term condition, increased three-fold in those with T2DM compared to those without (Feng et al., 2022). Thus, any deterioration in skeletal muscle health arising from the prescription of SGLT2i’s or GLP-1’s is of upmost concern. However, the mechanisms through which both drug classes influence skeletal muscle are poorly understood at present, with few studies conducted in humans. 

Therefore, this scoping review aims to describe the current literature concerning how SGLT2i and GLP-1’s modulates skeletal muscle, while highlighting gaps in the literature to inform future work in this area.