Effects of empagliflozin on reproductive system in men without diabetes.

Sodium-glucose cotransporter (SGLT) 2 inhibition is a well-known target for the treatment of type 2 diabetes, renal disease and chronic heart failure. The protein SGLT2 is encoded by SLC5A2 (Solute Carrier Family 5 Member 2), which is highly expressed in renal cortex, but also in the testes where glucose uptake may be essential for spermatogenesis and androgen synthesis. We postulated that in healthy males, SGLT2 inhibitor therapy may affect gonadal function. We examined the impact on gonadal and steroid hormones in a post-hoc analysis of a double-blind, randomized, placebo-controlled research including 26 healthy males who were given either placebo or empagliflozin 10 mg once daily for four weeks. After one month of empagliflozin, there were no discernible changes in androgen, pituitary gonadotropin hormones, or inhibin B. Regardless of BMI category, the administration of empagliflozin, a highly selective SGLT2 inhibitor, did not alter serum androgen levels in men without diabetes. While SGLT2 is present in the testes, its inhibition does not seem to affect testosterone production in Leydig cells nor inhibin B secretion by the Sertoli cells.

Enhancing fetal outcomes in GCK-MODY pregnancies: a precision medicine approach via non-invasive prenatal GCK mutation detection.

Background: Mutations in the GCK gene cause Maturity Onset Diabetes of the Young (GCK-MODY) by impairing glucose-sensing in pancreatic beta cells. During pregnancy, managing this type of diabetes varies based on fetal genotype. Fetuses carrying a GCK mutation can derive benefit from moderate maternal hyperglycemia, stimulating insulin secretion in fetal islets, whereas this may cause macrosomia in wild-type fetuses. Modulating maternal glycemia can thus be viewed as a form of personalized prenatal therapy, highly beneficial but not justifying the risk of invasive testing. We therefore developed a monogenic non-invasive prenatal diagnostic (NIPD-M) test to reliably detect the transmission of a known maternal GCK mutation to the fetus. Methods: A small amount of fetal circulating cell-free DNA is present in maternal plasma but cannot be distinguished from maternal cell-free DNA. Determining transmission of a maternal mutation to the fetus thus implies sequencing adjacent polymorphisms to determine the balance of maternal haplotypes, the transmitted haplotype being over-represented in maternal plasma. Results: Here we present a series of such tests in which fetal genotype was successfully determined and show that it can be used to guide therapeutic decisions during pregnancy and improve the outcome for the offspring. We discuss several potential hurdles inherent to the technique, and strategies to overcome these. Conclusion: Our NIPD-M test allows reliable determination of the presence of a maternal GCK mutation in the fetus, thereby allowing personalized in utero therapy by modulating maternal glycemia, without incurring the risk of miscarriage inherent to invasive testing.

The differential impact of a 6-versus 12-month pharmacist-led interprofessional medication adherence program on medication adherence in patients with diabetic kidney disease: the randomized PANDIA-IRIS study.

Background: For every 100 patients with diabetes, 40 will develop diabetic kidney disease (DKD) over time. This diabetes complication may be partly due to poor adherence to their prescribed medications. In this study, we aimed to evaluate the differential impact of a 6- versus 12-month pharmacist-led interprofessional medication adherence program (IMAP) on the components of adherence (i.e., implementation and discontinuation) in patients with DKD, during and after the intervention. Methods: All included patients benefited from the IMAP, which consists in face-to-face regular motivational interviews between the patient and the pharmacist based on the adherence feedback from electronic monitors (EMs), in which the prescribed treatments were delivered. Adherence reports were available to prescribers during the intervention period. Patients were randomized 1:1 into two parallel arms: a 12-month IMAP intervention in group A versus a 6-month intervention in group B. Adherence was monitored continuously for 24 months post-inclusion during the consecutive intervention and follow-up phases. In the follow-up phase post-intervention, EM data were blinded. Blood pressure was measured by the pharmacist at each visit. The repeated measures of daily patient medication intake outcomes (1/0) to antidiabetics, antihypertensive drugs, and statins were modeled longitudinally using the generalized estimated equation in both groups and in both the intervention and the follow-up phases. Results: EM data of 72 patients were analyzed (34 in group A and 38 in group B). Patient implementation to antidiabetics and antihypertensive drugs increased during the IMAP intervention phase and decreased progressively during the follow-up period. At 12 months, implementation to antidiabetics was statistically higher in group A versus group B (93.8% versus 86.8%; Δ 7.0%, 95% CI: 5.7%; 8.3%); implementation to antihypertensive drugs was also higher in group A versus B (97.9% versus 92.1%; Δ 5.8%, 95% CI: 4.8%; 6.7%). At 24 months, implementation to antidiabetics and antihypertensive drugs remained higher in group A versus B (for antidiabetics: 88.6% versus 85.6%; Δ 3.0%, 95% CI: 1.7%; 4.4% and for antihypertensive drugs: 94.4% versus 85.9%; Δ 8.5%, 95% CI: 6.6%; 10.7%). No difference in pharmacy-based blood pressure was observed between groups. Implementation to statins was comparable at each time point between groups. Three patients discontinued at least one treatment; they were all in group B. In total, 46% (16/35) of patients in the 12-month intervention versus 37% (14/38) of patients in the 6-month intervention left the study during the intervention phase, mainly due to personal reasons. Conclusion: The IMAP improves adherence to chronic medications in patients with DKD. The longer the patients benefit from the intervention, the more the implementation increases over time, and the more the effect lasts after the end of the intervention. These data suggest that a 12-month rather than a 6-month program should be provided as a standard of care to support medication adherence in this population. The impact on clinical outcomes needs to be demonstrated. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04190251_PANDIA IRIS.

Blood pressure and vascular determinants of glomerular filtration rate decline in diabetic kidney disease.

Objective: In patients with type 2 diabetes and diabetic kidney disease (DKD), explore the relationship between estimated glomerular filtration rate decline (eGFR-d) and simultaneously assessed vascular risk markers including office, ambulatory or central blood pressure, pulse pressure, carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (IMT) and renal resistive indexes (RRI). Research design and methods: At baseline, vascular risk markers were measured in addition to the routine clinical workup. The eGFR-d was based on 2000-2019 creatinine values. Parameters were compared by eGFR-d quartiles. Regression models of eGFR-d and vascular markers were assessed. Results: In total, 135 patients were included. Mean age was 63.8 ± 10.8y, baseline eGFR 60.2 ± 26.4 ml/min/1.73 m2 and urine albumin-creatinine ratio (ACR) 49 ± 108 mg/mmol. Mean eGFR-d was based on 43 ± 39 creatinine values within a time span of 7.0 ± 1.9y. The average yearly eGFR decline was -1.8 ± 3.0 ml/min/1.73 m2 ranging from -5.8 ± 2.3 in the first quartile to +1.4 ± 1.7 in the fourth quartile. Mean 24 h systolic (SBP) and diastolic (DBP) blood pressure were 126 ± 17 and 74 ± 9 mmHg. Mean PWV was 11.8 ± 2.8 m/s, RRI 0.76 ± 0.07 and IMT 0.77 ± 0.21 mm. SBP and pulse pressure correlated with eGFR-d but not DBP. 24 h SBP stood out as a stronger predictor of eGFR-d than office or central SBP. PWV and RRI correlated with eGFR decline in univariate, but not multivariate regression models including 24 SBP and ACR. Conclusions: In this study, eGFR decline was highly variable in patients with type 2 diabetes and DKD. Twenty-four hour SBP provided an added value to the routine measurement of ACR in predicting eGFR decline, whereas PWV and RRI did not.

Translation of the Diabetes Knowledge Questionnaire into French and its validation / Traduction et validation en langue française de l'instrument « Diabetes Knowledge Questionnaire ¼

Introduction: Improving patients' knowledge of diabetes would support adherence to treatment, prevent complications, and promote shared decision-making. Healthcare professionals need to assess patients' knowledge using a validated questionnaire in the local language. Objective: The aim of the study was to translate the Diabetes Knowledge Questionnaire from English to French and assess the psychometric properties of the translated version. Methods: A cross-sectional method was used. Individuals with diabetes were recruited from diabetes clinics, as well as dialysis units, since approximately 30 percent of dialysis patients have diabetes. Participants with type 1 or type 2 diabetes completed the translated questionnaire. The questionnaire targeted both groups, with additional questions for those with type 1 diabetes. Reliability and validity were assessed according to COSMIN approach. Results: Analysis of the translated questionnaire (n=102) showed good internal consistency (α=0.77), similar to the original questionnaire. The removal of an item on the self-monitoring of blood glucose increased the α Cronbach coefficient by 0.03. Discussion: Despite its validation, the questionnaire should be updated according to new clinical and medical recommendations to ensure consistency between the desired knowledge and the intended goals of care. Conclusion: The French version of the Diabetes Knowledge Questionnaire demonstrated good validity and reliability. It can be used in practice and research, after deleting item 9.

Introduction: L'amélioration des connaissances des patients sur le diabète pourrait soutenir leur adhésion au traitement, prévenir les complications et favoriser la prise de décision partagée. Les professionnels de la santé ont besoin d'évaluer les connaissances des patients à l'aide d'un questionnaire validé dans la langue locale. Objectif: L'étude avait pour but de traduire le Diabetes Knowledge Questionnaire en français et d'évaluer les qualités psychométriques de la version traduite. Méthodes: Dans cette étude transversale, les personnes diabétiques ont été recrutées dans les services de diabétologie, ainsi que dans les services de dialyse, car environ 30 % des patients dialysés sont diabétiques. Les participants diabétiques de type 1 ou 2 ont répondu au questionnaire traduit, le questionnaire s'adressant aux deux populations, avec des questions supplémentaires pour les diabétiques de type 1. La fidélité et la validité ont été évaluées selon la démarche COSMIN. Résultats: L'analyse du questionnaire traduit (n = 102) a montré une bonne cohérence interne (α = 0,77), similaire au questionnaire d'origine. La suppression d'un item portant sur les autocontrôles de glycémie a augmenté le coefficient α Cronbach de 0,03. Discussion: Malgré sa validation, le questionnaire mériterait une mise à jour selon les nouvelles pratiques et recommandations médicales, pour garantir une cohérence entre les connaissances souhaitées et les objectifs de soins visés. Conclusion: La version française du Diabetes Knowledge Questionnaire a démontré une bonne validité et fidélité, et peut être utilisée dans la pratique et la recherche, après la suppression de l'item n° 9.

[Diabetic nephropathy: Interprofessional support of medication adherence]. / Néphropathie diabétique : soutenir l'adhésion médicamenteuse de façon interprofessionnelle.

Medication non-adherence in patients with diabetic kidney disease (DKD) is endemic. The PANDIA-IRIS study, implemented at the community pharmacy of Unisanté, illustrates the support of medication adherence in patients with DKD by pharmacists, through an interprofessional program (IMAP) based on a behavioral science theoretical framework. Implementing behavioural support programmes such as PANDIA-IRIS on a large scale in Switzerland is both a necessity and a challenge. These programmes should be an integral part of standard patient care. The transition of care towards interprofessional collaborations and a clarification of roles in supporting adherence, including the patient as a partner, will contribute to fully considering adherence in therapeutic decision making and support to enable better achievement of long-term clinical goals.

La non-adhésion médicamenteuse chez les patient-es avec une néphropathie diabétique (ND) est endémique. L'étude PANDIA-IRIS, implémentée à la pharmacie communautaire d'Unisanté, illustre le soutien de l'adhésion des patient-es avec ND par des pharmacien-nes, au travers d'un programme interprofessionnel (IMAP) fondé sur un cadre théorique des sciences du comportement. Mettre en place des programmes d'accompagnement comportemental comme PANDIA-IRIS à large échelle en Suisse est à la fois une nécessité et un défi. Ces programmes devraient faire partie intégrante des soins standards des patient-es. La transition des soins vers des collaborations interprofessionnelles et une clarification des rôles dans le soutien de l'adhésion, incluant le-la patient-e comme partenaire, contribueront à considérer pleinement l'adhésion dans la prise de décisions thérapeutiques et dans son accompagnement pour permettre une meilleure atteinte des objectifs cliniques à long terme.

Diabetic kidney disease in type 2 diabetes: a consensus statement from the Swiss Societies of Diabetes and Nephrology.

Diabetic kidney disease is highly prevalent in patients with type 2 diabetes and is a major cause of end-stage renal disease in Switzerland. Patients with diabetic kidney disease are among the most complex patients in diabetes care. They require a multifactorial and multidisciplinary approach with the goal to slow the decline in glomerular filtration rate (GFR) and cardiovascular morbidity. With this consensus we propose an evidence-based guidance to health care providers involved in the care of type 2 diabetic patients with diabetic kidney disease.First, there is a need to increase physician awareness and improve screening for diabetic kidney disease as early intervention may improve clinical outcomes and the financial burden. Evaluation of estimated GFR (eGFR) and spot urine albumin/creatinine ratio is recommended at least annually. Once it is diagnosed, glucose control and optimisation of blood pressure control with renin-angiotensin system blockers have been recommended as mainstay management of diabetic kidney disease for more than 20 years. Recent, high quality randomised controlled trials have shown that sodium-glucose cotransporter-2 (SGLT2) inhibition slows eGFR decline and cardiovascular events beyond glucose control. Likewise, mineralocorticoid receptor antagonism with finerenone has cardiorenal protective effects in diabetic kidney disease. Glucagon-like peptide-1 (GLP1) receptor agonists improve weight loss if needed, and decrease albuminuria and cardiovascular morbidity. Lipid control is also important to decrease cardiovascular events. All these therapies are included in the treatment algorithms proposed in this consensus. With advancing kidney failure, other challenges may rise, such as hyperkalaemia, anaemia and metabolic acidosis, as well as chronic kidney disease-mineral and bone disorder. These different topics and treatment strategies are discussed in this consensus. Finally, an update on diabetes management in renal replacement therapy such as haemodialysis, peritoneal dialysis and renal transplantation is provided. With the recent developments of efficient therapies for diabetic kidney disease, it has become evident that a consensus document is necessary. We are optimistic that it will significantly contribute to a high-quality care for patients with diabetic kidney disease in Switzerland in the future.

[How is the management of diabetic hypertensive patients different?] / En quoi la prise en charge de l'hypertendu diabétique est-elle différente?

High blood pressure (HBP) is common in diabetic patients and significantly increases complications of diabetes and cardiovascular risk. It is therefore particularly important to routinely screen and treat HBP in these patients. Blood pressure targets in this population (<130/80mmHg) should be adapted to age and comorbidities. The therapeutic strategy has expanded beyond renin-angiotensin-aldosterone system inhibitors in the diabetic population, with treatments which decrease cardiovascular and renal risk, such as SGLT2 inhibitors, GLP-1 receptor agonists, and soon finerenone.

L'hypertension artérielle (HTA) est fréquente chez les patients diabétiques et augmente de manière considérable les complications du diabète et le risque cardiovasculaire. Il est donc particulièrement important de dépister de manière systématique et de traiter l'HTA chez ces patients. Les cibles tensionnelles dans cette population (< 130/80 mmHg) doivent être adaptées à l'âge et aux comorbidités. Dans la population diabétique, l'arsenal thérapeutique s'est élargi au-delà des inhibiteurs du système rénine-angiotensine-aldostérone, avec des traitements qui influencent le pronostic cardiovasculaire et rénal, comme c'est le cas pour les inhibiteurs du SGLT2, les agonistes des récepteurs du GLP-1 et, bientôt, la finérénone.

Understanding reasons and factors for participation and non-participation to a medication adherence program for patients with diabetic kidney disease in Switzerland: a mixed methods study.

BACKGROUND: An interprofessional medication adherence intervention led by pharmacists, combining motivational interviews and feedback with electronic monitor (EM) drug assessment, was offered to all consecutive patients with diabetic kidney disease (DKD) (estimated glomerular filtration rate < 60 mL/min/1.73 m2) visiting their nephrologist or endocrinologist. Approximately 73% (202/275) of eligible patients declined to participate, and the factors and reasons for refusal were investigated. METHODS: Sociodemographic and clinical data of included patients and those who refused were collected retrospectively for those who had previously signed the general consent form. Multivariate logistic regression analysis was performed to identify independent variables associated with non-participation. Patients who refused or accepted the adherence study were invited to participate in semi-structured interviews. Verbatim transcription, thematic analysis, and inductive coding were performed. RESULTS: Patients who refused to participate were older (n = 123, mean age 67.7 years, SD:10.4) than those who accepted (n = 57, mean age 64.0 years, SD:10.0, p = 0.027) and the proportion of women was higher among them than among patients who accepted it (30.9% vs 12.3%, p = 0.007). The time from diabetes diagnosis was longer in patients who refused than in those who accepted (median 14.2 years IQR 6.9-22.7 vs. 8.6 years, IQR 4.5-15.9, p = 0.003). Factors associated with an increased risk of non-participation were female sex (OR 3.8, 95% CI 1.4-10.0, p = 0.007) and the time from diabetes diagnosis (OR 1.05, 95% CI 1.01-1.09, p = 0.019). The included patients who were interviewed (n = 14) found the interprofessional intervention useful to improve their medication management, support medication literacy, and motivation. Patients who refused to participate and who were interviewed (n = 16) explained no perceived need, did not agree to use EM, and perceived the study as a burden and shared that the study would have been beneficial if introduced earlier in their therapeutic journey. Other barriers emerged as difficult relationships with healthcare providers, lack of awareness of the pharmacist's role, and negative perception of clinical research. CONCLUSIONS: Investigating the factors and reasons for participation and non-participation in a study helps tailor intervention designs to the needs of polypharmacy patients. Patients who refused the adherence intervention may not be aware of the benefits of medication management and medication literacy. There is an urgent need to advocate for interprofessional outpatient collaborations to support medication adherence in patients with DKD. Trial registration Clinicaltrials.gov NCT04190251_PANDIA IRIS.

Medication Adherence Evaluated Through Electronic Monitors During the 2020 COVID-19 Pandemic Lockdown in Switzerland: A Longitudinal Analysis.

Background: During the 2020 COVID-19 lockdown, patients included in the Interprofessional Medication Adherence Program (IMAP) in Switzerland continued to use electronic monitors (EMs) that registered daily drug-dose intake. We aimed to understand to what extent patients' medication implementation (ie, the extent to which the patient took the prescribed medicine), measured with EMs, was impacted by the lockdown. Methods: Patients participating in the IMAP were diagnosed with diabetic kidney disease (DKD), solid cancer, human immunodeficiency virus (HIV) and miscellaneous long-term diseases (MLTD). Patient implementation was defined through a proxy: if all patient EMs were opened at least once daily, implementation was considered active (=1), and no implementation was considered (=0) otherwise. Implementation before (from December 2019 to March 2020), during (March to June 2020) and after (June to September 2020) the lockdown was compared. Subanalyses were performed according to the patients' diseases. Subanalyses were performed in patients who used at least one EM in 2018-2019 during the same periods (defined as winter, spring and summer). The logistic regression models used to estimate medication implementation according to the period were fitted using generalized estimating equations. Results: In 2020, patient implementation (n = 118) did not differ significantly before versus during (OR = 0.98, 95% CI: 0.84-1.15, p = 0.789) and before versus after (OR = 0.91, 95% CI: 0.79-1.06, p = 0.217) the lockdown. These findings remained stable when separately analyzing the implementation of patients with HIV (n = 61), DKD (n = 25) or MLTD (n = 22). Too few patients with cancer were included (n = 10) to interpret the results. In 2019, the implementation of 61/118 (51.7%) patients was significantly lower during summertime versus wintertime (OR = 0.73, 95% CI: 0.60-0.89, p = 0.002). Conclusion: Medication implementation remained steady before, during and after the lockdown in 2020. The IMAP before, during and after the lockdown may have supported the adherence of most patients, by ensuring continuity of care during periods of routine disturbances.

Metformin versus SGLT-2 inhibitors: how low can we go?

The progression of chronic kidney disease is difficult to stop once established. Metformin and sodium-glucose cotransporter 2 inhibitors show promise, but clinical trials with a head-to-head comparison in patients with more advanced (stage 3b-4) chronic kidney disease are largely lacking, partly for safety reasons. In this issue, Corremans et al. compare the effects of metformin and canagliflozin in rats with adenine-induced moderate (stage 2-4) chronic kidney disease. Metformin halted progression, whereas canagliflozin did not. This commentary puts the results in a wider clinical context.

Empagliflozin Changes Urine Supersaturation by Decreasing pH and Increasing Citrate.

Clinical Trial registry name and registration number: Empagliflozin and Renal Oxygenation in Healthy Volunteers (EMPA-REIN), NCT03093103.

Twenty-Four Hour Blood Pressure Response to Empagliflozin and Its Determinants in Normotensive Non-diabetic Subjects.

Background: Sodium-glucose co-transport 2 inhibitors (SGLT2i) lower blood pressure (BP) in normotensive subjects and in hypertensive and normotensive diabetic and non-diabetic patients. However, the mechanisms of these BP changes are not fully understood. Therefore, we examined the clinical and biochemical determinants of the BP response to empagliflozin based on 24-h ambulatory BP monitoring. Methods: In this post-hoc analysis of a double-blind, randomized, placebo-controlled study examining the renal effects of empagliflozin 10 mg vs. placebo in untreated normotensive non-diabetic subjects, the 1-month changes in 24 h ambulatory BP were analyzed in 39 subjects (13 placebo/26 empagliflozin) in regard to changes in biochemical and hormonal parameters. Results: At 1 month, empagliflozin 10 mg decreased 24-h systolic (SBP) and diastolic (DBP) BP significantly by -5 ± 7 mmHg (p < 0.001) and -2 ± 6 mmHg (p = 0.03). The effect on SBP and DBP was more pronounced during nighttime (resp. -6 ± 11 mmHg, p = 0.004; -4 ± 7 mmHg, p = 0.007). The main determinants of daytime and nighttime SBP and DBP responses were baseline BP levels (for daytime SBP: coefficient -0.5; adj. R2: 0.36; p = 0.0007; for night-time SBP: coefficient -0.6; adj. R2: 0.33; p = 0.001). Although empaglifozin induced significant biochemical changes, none correlated with blood pressure changes including urinary sodium, lithium, glucose and urate excretion and free water clearance. Plasma renin activity and plasma aldosterone levels increased significantly at 1 month suggesting plasma volume contraction, while plasma metanephrine and copeptin levels remained the same. Renal resistive indexes did not change with empagliflozin. Conclusion: SGLT2 inhibition lowers daytime and nighttime ambulatory systolic and diastolic BP in normotensive non-diabetic subjects. Twenty-four jour changes are pronounced and comparable to those described in diabetic or hypertensive subjects. Baseline ambulatory BP was the only identified determinant of systolic and diastolic BP response. This suggests that still other factors than sustained glycosuria or proximal sodium excretion may contribute to the resetting to lower blood pressure levels with SGLT2 inhibition. Clinical Trial Registration: [https://www.clinicaltrials.gov], identifier [NCT03093103].

SGLT2 Inhibitors, What the Emergency Physician Needs to Know: A Narrative Review.

Canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin belong to a class of antidiabetic treatments referred to as sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors, or SGLT2is). SGLT2is are currently indicated in North America and in Europe in type 2 diabetes mellitus, especially in patients with cardiovascular (CV) disease, high CV risk, heart failure, or renal disease. In Europe, dapagliflozin is also approved as an adjunct to insulin in patients with type 1 diabetes mellitus. New data provide evidence for benefits in heart failure with reduced ejection fraction and chronic kidney disease, including in patients without diabetes. The use of SGLT2is is expected to increase, suggesting that a growing number of patients will present to the emergency departments with these drugs. Most common adverse events are easily treatable, including mild genitourinary infections and conditions related to volume depletion. However, attention must be paid to some potentially serious adverse events, such as hypoglycemia (when combined with insulin or insulin secretagogues), lower limb ischemia, and diabetic ketoacidosis. We provide an up-to-date practical guide highlighting important elements on the adverse effects of SGLT2is and their handling in some frequently encountered clinical situations such as acute heart failure and decompensated diabetes.

Interprofessional Medication Adherence Program for Patients With Diabetic Kidney Disease: Protocol for a Randomized Controlled and Qualitative Study (PANDIA-IRIS).

BACKGROUND: Despite effective treatments, more than 30% of patients with diabetes will present with diabetic kidney disease (DKD) at some point. Patients with DKD are among the most complex as their care is multifactorial and involves different groups of health care providers. Suboptimal adherence to polypharmacy is frequent and contributes to poor outcomes. As self-management is one of the keys to clinical success, structured medication adherence programs are crucial. The PANDIA-IRIS (patients diabétiques et insuffisants rénaux: un programme interdisciplinaire de soutien à l'adhésion thérapeutique) study is based on a routine medication adherence program led by pharmacists. OBJECTIVE: The aim of this study is to define the impact of the duration of this medication adherence program on long-term adherence and clinical outcomes in patients with DKD. METHODS: This monocentric adherence program consists of short, repeated motivational interviews focused on patients' medication behaviors combined with the use of electronic monitors containing patients' medications. When patients open the electronic monitor cap to take their medication, the date and hour at each opening are registered. In total, 73 patients are randomized as 1:1 in 2 parallel groups; the adherence program will last 6 months in the first group versus 12 months in the second group. After the intervention phases, patients continue using their electronic monitors for a total of 24 months but without receiving feedback. Electronic monitors and pill counts are used to assess medication adherence. Persistence and implementation will be described using Kaplan-Meier curves and generalized estimating equation multimodeling, respectively. Longitudinal adherence will be presented as the product of persistence and implementation and modelized by generalized estimating equation multimodeling. The evolution of the ADVANCE (Action in Diabetes and Vascular disease: Preterax and Diamicron Modified-Release Controlled Evaluation) and UKPDS (United Kingdom Prospective Diabetes Study) clinical scores based on medication adherence will be analyzed with generalized estimating equation multimodeling. Patients' satisfaction with this study will be assessed through qualitative interviews, which will be transcribed verbatim, coded, and analyzed for the main themes. RESULTS: This study was approved by the local ethics committee (Vaud, Switzerland) in November 2015. Since then, 2 amendments to the protocol have been approved in June 2017 and October 2019. Patients' recruitment began in April 2016 and ended in October 2020. This study was introduced to all consecutive eligible patients (n=275). Among them, 73 accepted to participate (26.5%) and 202 (73.5%) refused. Data collection is ongoing and data analysis is planned for 2022. CONCLUSIONS: The PANDIA-IRIS study will provide crucial information about the impact of the medication adherence program on the adherence and clinical outcomes of patients with DKD. Monitoring medication adherence during the postintervention phase is innovative and will shed light on the duration of the intervention on medication adherence. TRIAL REGISTRATION: Clinicaltrials.gov NCT04190251_PANDIA IRIS; https://clinicaltrials.gov/ct2/show/NCT04190251. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25966.

[SGLT2 inhibitors in diabetic and non-diabetic nephropathies]. / Inhibiteurs du SGLT2 dans les néphropathies diabétiques et non diabétiques.

SGLT2 inhibitors (SGLT2i) will change the clinical practice of nephrology with their therapeutic cardiorenal and antidiabetic properties. By inhibiting proximal tubular sodium and glucose reabsorption, these new drugs decrease intraglomerular pressures. Over the last 5 years several breakthrough studies have demonstrated the SGLT2i protective effects on outcomes such as cardiovascular mortality, hospital admission for heart failure, sustained decreases in eGFR in patients with diabetic nephropathy and the development of ESKD. With the new DAPA-CKD study revealing protective effects of SGLT2i in CKD patients without diabetes, therapeutic recommendations will now have to evolve towards including these drugs in the chronic management of all most proteinuric CKD patients.

Les inhibiteurs du cotransporteur du sodium-glucose de type 2 (iSGLT2) révolutionnent la pratique clinique en néphrologie par le biais de leurs effets antidiabétique, cardio et néphroprotecteur. Ces molécules inhibent la réabsorption du glucose et du sodium au niveau du tubule proximal, ce qui résulte en une baisse de la pression intraglomérulaire. Plusieurs grandes études ont démontré l'effet protecteur des iSGLT2 sur la mortalité cardiovasculaire, le taux d'hospitalisation pour une insuffisance cardiaque et le ralentissement de la progression de la néphropathie diabétique. La sortie de DAPA-CKD va certainement modifier les recommandations thérapeutiques pour la prise en charge de l'insuffisance rénale chronique (IRC) non diabétique, en démontrant un effet néphroprotecteur majeur chez les IRC protéinuriques d'origine non diabétique également.

A Multidisciplinary Approach for Improving Quality of Life and Self-Management in Diabetic Kidney Disease: A Crossover Study.

Individuals with diabetic kidney disease are at high risk of complications and challenged to self-manage. Previous research suggested that multidisciplinary approaches would improve health outcomes. This study investigated the effect of a multidisciplinary self-management approach of diabetic kidney disease on quality of life, and self-management, glycemic control, and renal function. A uniform balanced crossover design was used because it attains a high level of statistical power with a lower sample size. A total of 32 participants (aged 67.8 ± 10.8) were randomized into four study arms. In differing sequences, each participant was treated twice with three months of usual care alternated with three months of multidisciplinary management. The intervention improved the present dimension of quality of life demonstrating higher mean rank as compared to usual care (52.49 vs. 41.01; p = 0.026, 95% CI) and three self-care activities, general diet habits, diabetes diet habits, and blood sugar testing (respectively: 55.43 vs. 38.31; p = 0.002, 56.84 vs. 37.02; p = 0.000, 53.84 vs. 39.77; p = 0.008; 95% CI). Antihypertensive medication engagement was high across the study period (Mean = 95.38%, Min = 69%, Max = 100%). Glycemic control and renal function indicators were similar for the intervention and the usual care. Studies are needed to determine how the new recommended therapies for diabetic kidney disease such as SGLT2 inhibitors and GLP-1 receptor agonists impact on self-management and quality of life.

[Post-transplantation diabetes in kidney transplant: from the diabetologist point of view]. / Diabète post-transplantation rénale: le point de vue du diabétologue.

Post-transplantation diabetes (PTDM) exposes to increased morbidity (cardiovascular or infectious complications, early graft dysfunction) and to a risk of premature death. Recognition of risk factors is essential for early and individualized care. The management of a PTDM requires the use of oral antidiabetic treatments (metformin or DPP4 inhibitors) or GLP1 receptor agonists for their favorable effects on weight and kidney that seem ideal in this context. Corticosteroid-induced diabetes or the rare occurrence of diabetic ketoacidosis require insulin therapy. In the long term, the main objective remains to integrate PTDM treatment in a more comprehensive management, targeting the reduction of cardiovascular risk of vulnerable transplant patients.

Le diabète post-transplantation (PTDM) expose le patient à une morbidité accrue (cardiovasculaire, infectieuse ou dysfonction précoce du greffon), ainsi qu'à un risque de décès prématuré. La reconnaissance des facteurs de risque est primordiale pour une prise en charge précoce et individualisée. La prise en charge d'un PTDM d'apparition progressive recourt à l'utilisation d'antidiabétiques oraux (metformine ou inhibiteurs de la dipeptidyl peptidase 4) ou aux agonistes du récepteur du glucagon-like peptide-1 dont l'effet pondéral et néphroprotecteur semble idéal dans ce contexte. Un diabète cortico-induit ou, plus rare, une acidocétose aiguë seront traités par une insulinothérapie précoce. À long terme, l'objectif reste d'intégrer le traitement du PTDM dans une prise en charge plus globale ciblant la réduction du risque cardiovasculaire de ces patients transplantés fragiles.

[Medication adherence and physician-pharmacist collaboration. Focus on the patient with diabetic nephropathy]. / Adhésion thérapeutique et collaboration médecin-pharmacien. L'exemple du patient avec néphropathie diabétique.

Polypharmacy is common in patients with a chronic disease. It is appropriate when both the patient and the physician discuss the goal of each prescribed medication with a motivated patient capable of managing his/her medication. It can however be inappropriate when treatment becomes too complex for the frail patient. The risk is non-adherence to therapy, which often results in an intensification of treatment due to unmet therapeutic goals. Collaboration between physicians and pharmacists is therefore essential for the educational support of patients with polypharmacy. In this article, we review the studies examining the impact of a physician-pharmacist collaboration on the medication adherence of diabetic patients with renal impairment.

La polypharmacie concerne de nombreux patients avec une maladie chronique. Elle est appropriée lorsque chaque médicament a été prescrit dans un but thérapeutique spécifique discuté avec un patient motivé et capable de gérer ses médicaments. Elle peut cependant être inappropriée lorsque le traitement devient trop complexe pour une personne fragile. Le risque est une non-adhésion au traitement, dont découle souvent une intensification de la thérapie en raison d'objectifs thérapeutiques non atteints. La collaboration médecin-pharmacien est donc primordiale pour l'accompagnement éducatif du patient complexe dans la gestion de ses médicaments. Dans cet article, nous revoyons les études examinant l'adhésion thérapeutique chez le patient diabétique avec une atteinte rénale lors d'une collaboration médecin-pharmacien.