Glucagon-like-1 receptor agonists and sodium/glucose cotransporter-2 inhibitors combination—are we exploiting their full potential in a real life setting?

BACKGROUND The sodium/glucose cotransporter-2 inhibitors(SGLT-2i)and glucagon-like-1 receptor agonists(GLP-1RA)are antidiabetic agents effective both in hemoglobin A1c(HbA1c)reduction(with a low risk of hypoglycemia)and cardiovascular event prevention.In patients with type 2 diabetes,the add-on value of combination therapy of GLP-1RA and an SGLT-2i seems promising.AIM To investigate whether the efficacy of GLP-1RA and SGLT-2i combination observed in randomized controlled trials translates into therapeutic benefits in the Croatian population during routine clinical practice and follow-up.METHODS We included 200 type 2 diabetes patients with poor glycemic control and analyzed the effects of treatment intensification with(1)GLP-1RA on top of SGLT-2i,(2)SGLT-2i on top of GLP-1RA compared to(3)simultaneous addition of both agents.The primary study endpoint was the proportion of participants with HbA1c<7.0%and/or 5%bodyweight reduction.Secondary outcomes included changes in fasting plasma glucose(FPG),prandial plasma glucose,lowdensity lipoprotein cholesterol,estimated glomerular filtration rate(eGFR),and cardiovascular(CV)incidents assessment over a follow-up period of 12 mo.RESULTS The majority of patients were over 65-years-old,had diabetes duration for more than 10 years.The initial body mass index was 39.41±5.49 kg/m2 and HbA1c 8.32±1.26%.Around half of the patients in all three groups achieved target HbA1c below 7%.A more pronounced decrease in the HbA1c seen with simultaneous SGLT-2i and GLP-1RA therapy was a result of higher baseline HbA1c and not the effect of initiating combination therapy.The number of patients achieving FPG below 7.0 mmol/L was significantly higher in the SGLT-2i group(P=0.021),and 5%weight loss was dominantly achieved in the simultaneous therapy group(P=0.044).A composite outcome(reduction of HbA1c below 7%(53 mmol/mol)with 5%weight loss)was achieved in 32.3%of total patients included in the study.Only 18.2%of patients attained composite outcome defined as HbA1c below 7%(53 mmol/mol)with 5%weight loss and low-density lipoprotein cholesterol<2.5 mmol/L.There were no significant differences between treatment groups.No differences were observed regarding CV incidents or eGFR according to treatment group over a follow-up period.CONCLUSION Combination therapy with GLP-1RA and SGLT-2i is effective in terms of metabolic control,although it remains to be determined whether simultaneous or sequential intensification is better.

Revealing driver psychophysiological response to emergency braking in distracted driving based on field experiments

Purpose–The purpose of this paper is to characterize distracted driving by quantifying the response time and response intensity to an emergency stop using the driver’s physiological states.Design/methodology/approach–Field tests with 17 participants were conducted in the connected and automated vehicle test field.All participants were required to prioritize their primary driving tasks while a secondary nondriving task was asked to be executed.Demographic data,vehicle trajectory data and various physiological data were recorded through a biosignalsplux signal data acquisition toolkit,such as electrocardiograph for heart rate,electromyography for muscle strength,electrodermal activity for skin conductance and force-sensing resistor for braking pressure.Findings–This study quantified the psychophysiological responses of the driver who returns to the primary driving task from the secondary nondriving task when an emergency occurs.The results provided a prototype analysis of the time required for making a decision in the context of advanced driver assistance systems or for rebuilding the situational awareness in future automated vehicles when a driver’s take-over maneuver is needed.Originality/value–The hypothesis is that the secondary task will result in a higher mental workload and a prolonged reaction time.Therefore,the driver states in distracted driving are significantly different than in regular driving,the physiological signal improves measuring the brake response time and distraction levels and brake intensity can be expressed as functions of driver demographics.To the best of the authors’knowledge,this is the first study using psychophysiological measures to quantify a driver’s response to an emergency stop during distracted driving.