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

Prediction of diabetic foot ulceration: The value of using microclimate sensor arrays

Background: Accurately predicting the risk of diabetic foot ulceration (DFU) could dramatically reduce the enormous burden of chronic wound management and amputation. Yet, current prognostic models are unable to precisely predict DFU events. Typically, efforts have focused on individual factors like temperature, pressure or shear rather than the overall foot microclimate. Method: A systematic review was conducted by searching PubMed reports with no restrictions on start date covering literature published until 20 February 2019 using relevant keywords, including temperature, pressure, shear and relative humidity. We review the use of these variables as predictors of DFU, highlighting gaps in our current understanding and suggesting which specific features should be combined to develop a real-time microclimate prognostic model. Results: Current prognostic models rely either solely on contralateral temperature, pressure or shear measurement; these parameters, however, rarely reach 50% specificity in relation to DFU. There is also considerable variation in methodological investigation, anatomical sensor configuration and resting time prior to temperature measurements (5-20 minutes). Few studies have considered relative humidity and mean skin resistance. Conclusions: Very limited evidence supports the use of single clinical parameters in predicting the risk of DFU. We suggest the microclimate as a whole should be considered to predict DFU more effectively and suggest nine specific features which appear to be implicated for further investigation. Technology supports real-time inshoe data collection and wireless transmission, providing a potentially rich source of data to better predict risk of DFU

Psoriasis and Psyche - What`s New? What is Clinically Relevant?

Physical activity and age-sex standardised prevalence of multimorbidity over time in the restricted sample (DOCX 16 kb

The Present & Future Scope of RWE Research in Diabetes: What Questions Can and Can’t Be Answered and What Might be Possible in the Future?

The last decade has witnessed an exponential growth in the opportunities to collect and link health-related data from multiple resources, including primary care, administrative, and device data. The availability of these “real-world”, “big data” has fuelled also an intense methodological research into methods to handle them and extract actionable information. In medicine, the evidence generated from “real-world data” (RWD), which are not purposely collected to answer biomedical questions, is commonly termed “real-world evidence” (RWE). In this review, we focus on RWD and RWE in the area of diabetes research, highlighting their contributions in the last decade; and give some suggestions for future RWE diabetes research, by applying well-established and less-known tools to direct RWE diabetes research towards better personalised approaches to diabetes care. We underline the essential aspects to consider when using RWD and the key features limiting the translational potential of RWD in generating high-quality and applicable RWE. Only if viewed in the context of other study designs and statistical methods, with its pros and cons carefully considered, RWE will exploit its full potential as a complementary or even, in some cases, substitutive source of evidence compared to the expensive evidence obtained from randomised controlled trials

Pharmaceutical Interventions for Diabetes Prevention in Patients at Risk

With the rising incidence and prevalence rates of type 2 diabetes globally, it is imperative that diabetes prevention strategies are implemented to stem the flow of new cases. Successful interventions include both lifestyle modification and pharmaceutical agents, and large, multicentre, randomised, controlled studies in different populations have identified the benefits of both. However, translating positive trial outcomes to the real world is particularly challenging, as lifestyle interventions require regular reinforcement from healthcare professionals to be maintained. Pharmaceutical therapies may therefore play an adjunctive role in combination with lifestyle to prevent diabetes. Population-based strategies are also necessary to reduce sedentary behaviour and obesity. Well-established glucose-lowering therapies such as metformin, sulphonylureas, thiazolidinediones and insulin and newer agents such as incretin therapies and sodium glucose co-transporter 2 inhibitors have all been investigated in randomised controlled trials for diabetes prevention with varying success. Non-glucose-lowering therapies such as orlistat and renin angiotensin system blockers can prevent diabetes, whereas statins are associated with slightly increased risk. Diabetes prevention strategies should carefully consider the use of these agents according to individual patient circumstances and phenotypic profile

The treatment of type 2 diabetes in the presence of renal impairment: what we should know about newer therapies

Worldwide, an estimated 200 million people have chronic kidney disease (CKD), the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2-5) and without dose adjustment; there are contraindications and dose adjustments required for the remaining standard therapies. Newer therapies, particularly dipeptidyl peptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors, are increasingly being used in the treatment of type 2 diabetes; however, a major consideration is whether these newer therapies can also be used safely and effectively across the spectrum of renal impairment. Notably, reductions in albuminuria, a marker of CKD, are observed with many of the drug classes. Dipeptidyl peptidase-IV inhibitors can be used in all stages of renal impairment, with appropriate dose reduction, with the exception of linagliptin, which can be used without dose adjustment. No dose adjustment is required for liraglutide, albiglutide, and dulaglutide in CKD stages 2 and 3, although all glucagon-like peptide-1 receptor agonists are currently contraindicated in stages 4 and 5 CKD. At stage 3 CKD or greater, the sodium-glucose cotransporter-2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) either require dose adjustment or are contraindicated. Ongoing trials, such as CARMELINA, MARLINA, CREDENCE, and CANVAS-R, will help determine the position of these new therapy classes and if they have renoprotective effects in patients with CKD

Authors' Reply to Gough: "Achieving Glycaemic Control with Concentrated Insulin in Patients with Type 2 Diabetes".

This reply refers to the letter available at doi: https://doi.org/10.1007/s40265-019-01092-2. We thank Dr Gough for his comments regarding our manuscript entitled “Achieving Glycaemic Control with Concentrated Insulin in Patients with Type 2 Diabetes” [1, 2]. We have addressed each comment separately below

A review of exenatide: optimizing glycemic control and associated cardiovascular risk factors in type 2 diabetes

Type 2 diabetes mellitus (T2DM) is a well-recognized risk factor for the development of cardiovascular disease. With an increasing prevalence of obesity, this risk has increased further. Management of T2DM in obese patients is particularly challenging as treatment with the majority of glucose-lowering agents results in weight gain. Thus, the development of a therapeutic option which could improve glycemic control without weight gain or hypoglycemia, such as the glucagon-like peptide-1 (GLP-1) analog exenatide, is a welcome addition to the currently available therapies in the management of T2DM. With recognition and better understanding of the role of incretin hormones in T2DM, exenatide was developed and introduced into clinical practice in 2005. Both randomized controlled trials and retrospective observational studies have shown that treatment with exenatide not only improves glycemic control, with a low risk of hypoglycemia, but also results in concurrent weight loss and the additional benefit of improvement in cardiovascular risk factors. This article will provide an overview of both short- and long-acting exenatide in the management of T2DM and associated cardiovascular risk factors

Association Between Adherence to Pharmacotherapy and Outcomes in Type 2 Diabetes: A Meta-analysis.

OBJECTIVE: A previous study suggests an association between poor medication adherence and excess mortality in chronic disease. The purpose of this study was to assess the association between medication adherence and risk of cardiovascular disease (CVD), all-cause mortality, and hospitalization in type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic search on many electronic databases from inception to 27 April 2016. We selected randomized controlled trials and case-control and cohort studies reporting on CVD, all-cause mortality, or hospitalization outcomes by adherence in adults with type 2 diabetes. Two reviewers independently screened for eligible studies and extracted outcome data. Pooled relative risks (RRs) were calculated using a random-effects meta-analysis; risk of bias in each of the included studies was assessed using the GRADE approach. RESULTS: Eight observational studies were included (n = 318,125). The mean rate of poor adherence was 37.8% (95% CI 37.6-38.0). Adjusted estimates were provided by five studies only. The RRs of good (≥80%) versus poor adherence to medication were 0.72 (95% CI 0.62-0.82, I2 = 0%, three studies) for all-cause mortality and 0.90 (0.87-0.94, I2 = 63%, seven studies) for hospitalization. No evidence of small study bias was observed. Only one study reported CVD outcomes by adherence. CONCLUSIONS: We identified no trials reporting on outcomes by adherence, suggesting a systematic failure to include this information. Pooled estimates from available observational studies suggest that good medication adherence is associated with reduced risk of all-cause mortality and hospitalization in people with type 2 diabetes, although bias cannot be excluded as an explanation for these findings

Number needed to treat in cardiovascular outcome trials with glucagon-like peptide-1 receptor agonists: A systematic review with temporal analysis

Cardiovascular outcome trials (CVOTs) investigating the safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have highlighted some important differences among these medications. The recent American Diabetes Association and European Association for the Study of Diabetes consensus underlines that each trial constitutes a single experiment; therefore, it remains unclear if, and to what extent, the observed differences reflect the heterogeneous pharmacological properties of each compound. To help clarify the evidence, in this systematic review we investigated differences in trial characteristics which may have had an impact on the primary and secondary trial results, including baseline control of risk factors, prevalence of cardiovascular diseases, absolute rates of events, duration of the study, and definitions of the inclusion criteria and outcomes. Aiming at enhancing the clinical interpretation of these CVOTs, we quantified the absolute treatment effect over time in terms of the number needed to treat to avoid one major adverse cardiovascular event, showing variations among GLP-1RAs.</p