Adherence and persistence to novel glucose-lowering medications in persons with type 2 diabetes mellitus undergoing routine care.

AIMS: To assess adherence and persistence to sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1-RA), and dipeptidyl peptidase-4 inhibitors (DPP4i) in routine care. METHODS: Using retrospective healthcare data from the Stockholm region, Sweden, we evaluated new-users of these agents during 2015-2020. We investigated adherence (≥80 % of days covered by an active supply), persistence (no treatment gap ≥ 60 days), and predictors for non-adherence and non-persistence. RESULTS: We identified 24,470 new-users of SGLT2i (10,743), GLP1-RA (10,315), and/or DPP4i (9,488). Over 2.8 years median follow-up, the proportion demonstrating adherence was higher for SGLT2i (57 %) than DPP4i (53 %, comparison p < 0.001), and for GLP1-RA than DPP4i (54 % vs 53 %, p < 0.001). Similarly, persistence was higher for both SGLT2i and GLP-RA than DPP4i (respectively, 50 % vs 44 %, p < 0.001; 49 % vs 44 %, p < 0.001). Overall adherence was better among users who were older, had a history of high blood pressure, used more non-diabetic medications, had lower Hba1c, had better kidney function, and had completed secondary schooling or university. Women had worse adherence to SGLT2i and GLP1-RA than DPP4i. CONCLUSIONS: We report adherence and persistence to SGLT2i, GLP1-RA and DPP4i in routine care, and identify prognostic factors that could inform implementation interventions to improve uptake of these important therapies.

Applications of SGLT2 inhibitors beyond glycaemic control.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were initially developed for their glucose-lowering effects and have shown a modest glycaemic benefit in people with type 2 diabetes mellitus (T2DM). In the past decade, a series of large, robust clinical trials of these therapies have demonstrated striking beneficial effects for various care goals, transforming the chronic disease therapeutic landscape. Cardiovascular safety studies in people with T2DM demonstrated that SGLT2 inhibitors reduce cardiovascular death and hospitalization for heart failure. Subsequent trials in participants with heart failure with reduced or preserved left ventricular ejection fraction demonstrated that SGLT2 inhibitors have beneficial effects on heart failure outcomes. In dedicated kidney outcome studies, SGLT2 inhibitors reduced the incidence of kidney failure among participants with or without diabetes. Post hoc analyses have suggested a range of other benefits of these drugs in conditions as diverse as metabolic dysfunction-associated steatotic liver disease, kidney stone prevention and anaemia. SGLT2 inhibitors have a generally favourable adverse effect profile, although patient selection and medication counselling remain important. Concerted efforts are needed to better integrate these agents into routine care and support long-term medication adherence to close the gap between clinical trial outcomes and those achieved in the real world.

Identifying Barriers and Facilitators for Increasing Uptake of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors in British Columbia, Canada, using the Consolidated Framework for Implementation Research.

Background: Care gaps remain in modern health care despite the availability of robust, evidence-based medications. Although sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated profound benefits in improving both cardiovascular and kidney outcomes in patients, the uptake of these medications remain suboptimal, and the causes have not been systematically explored. Objective: The purpose of this study was to use the Consolidated Framework for Implementation Research (CFIR) to describe the barriers and facilitators faced by clinicians in British Columbia, Canada, when prescribing an SGLT2 inhibitor. To achieve this, we conducted semistructured interviews using the CFIR with practicing family physicians, nephrologists, endocrinologists, and cardiologists in British Columbia. Design: Semistructured interviews. Setting: British Columbia, Canada. Participants: Actively practicing family physicians, nephrologists, endocrinologists, and cardiologists in British Columbia. Methods: Twenty-one clinicians were interviewed using questions derived from the CFIR. The audio recordings were transcribed verbatim, and each transcription was individually analyzed in duplicate using thematic analysis. The analysis focused on identifying barriers and facilitators to using SGLT2 inhibitors in clinical practice and coded using the CFIR constructs. Once the transcriptions were coded, overarching themes were created. Results: Five overarching themes were identified to the barriers and facilitators to using SGLT2 inhibitors: current perceptions and beliefs, clinician factors, patient factors, medication factors, and health care system factors. The current perceptions and beliefs were that SGLT2 inhibitors are efficacious and have distinct advantages over other agents but are underutilized in British Columbia. Clinician factors included varying levels of knowledge of and comfort in prescribing SGLT2 inhibitors, and patient factors included intolerable adverse events and additional pill burden, but many were enthusiastic about potential benefits. Multiple SGLT2 inhibitor related adverse events like mycotic infections and euglycemic diabetic ketoacidosis and the difficulty in obtaining reimbursement for these medications were also identified as a barrier to prescribing these medications. Facilitators for the use of SGLT2 inhibitors included consensus among colleagues, influential leaders, and peers in support of their use, and endorsement by national guidelines. Limitations: The experience from the clinicians regarding costs and the reimbursement process is limited to British Columbia as each province has its own procedures. There may be responder bias as clinicians were approached through purposive sampling. Conclusion: This study highlights different themes to the barriers and facilitators of using SGLT2 inhibitors in British Columbia. The identification of these barriers provides a specific target for improvement, and the facilitators can be leveraged for the increased use of SGLT2 inhibitors. Efforts to address and optimize these barriers and facilitators in a systematic approach may lead to an increase in the use of these efficacious medications.

Contexte: Des lacunes subsistent dans les soins de santé modernes, malgré l'existence de médicaments éprouvés et fondés sur des données probantes. Les inhibiteurs du cotransporteur de sodium-glucose de type 2 (SGLT2) ont démontré d'importants effets dans l'amélioration des résultats cardiovasculaires et rénaux des patients, mais l'utilization de ces médicaments demeure sous-optimale et les raisons qui expliquent cette situation n'ont pas été systématiquement explorées. Objectif: Utiliser le Consolidated Framework for Implementation Research (CFIR) pour décrire les obstacles et les éléments facilitateurs rencontrés par les cliniciens de la Colombie-Britannique (Canada) lorsqu'ils prescrivent un inhibiteur du SGLT2. Pour ce faire, nous avons mené des entretiens semi-structurés au moyen du CFIR auprès de médecins de famille, de néphrologues, de cardiologues et d'endocrinologues exerçant en Colombie-Britannique. Conception: Entretiens semi-structurés. Cadre: Colombie-Britannique (Canada). Participants: Médecins de famille, cardiologues, endocrinologues et néphrologues exerçant en Colombie-Britannique. Méthodologie: Les questions dérivées du CFIR ont été posées à vingt-et-un cliniciens. Les enregistrements audio ont été transcrits verbatim et chaque transcription a été analysée individuellement en double en utilisant l'analyze thématique. L'analyze s'est concentrée sur l'identification des obstacles et des facilitateurs à l'utilization des inhibiteurs du SGLT2 dans la pratique clinique et sur le codage selon les concepts du CFIR. Une fois les transcriptions codées, des thèmes généraux ont été créés. Résultats: Cinq thèmes généraux ont été identifiés pour les obstacles et les facilitateurs à l'utilization des inhibiteurs du SGLT2: les perceptions et les croyances actuelles, les facteurs liés aux cliniciens, les facteurs liés aux patients, les facteurs liés aux médicaments et les facteurs liés au système de santé. Les perceptions et croyances actuelles étaient que les inhibiteurs du SGLT2 sont efficaces, qu'ils présentent des avantages distincts des autres agents, mais qu'ils sont sous-utilisés en Colombie-Britannique. Les facteurs liés aux cliniciens incluaient des niveaux variables de connaissance et de confort vis-à-vis la prescription d'inhibiteurs du SGLT2. Les facteurs liés aux patients incluaient les événements indésirables intolérables et la charge médicamenteuse supplémentaire, mais plusieurs répondants voyaient positivement les bienfaits potentiels. Les nombreux événements indésirables liés aux inhibiteurs du SGLT2, notamment les infections mycosiques et l'acidocétose diabétique euglycémique, et la difficulté à obtenir le remboursement de ces médicaments ont également été cités comme raisons limitant la prescription de ces médicaments. Le consensus parmi les collègues, les leaders influents et les pairs en faveur des inhibiteurs du SGLT2 et l'inclusion de ces médicaments dans les lignes directrices nationales figuraient parmi les facilitateurs. Limites: Les expériences rapportées par les cliniciens en ce qui concerne les coûts et le processus de remboursement se limitent à la Colombie-Britannique, car chaque province a ses propres procédures. L'étude comporte un possible biais de réponse puisque les cliniciens ont été approchés par échantillonnage dirigé. Conclusion: Cette étude met en évidence différents thèmes concernant les obstacles et les facilitateurs à l'utilization des inhibiteurs du SGLT2 en Colombie-Britannique. L'identification de ces obstacles fournit une cible précise pour l'amélioration, alors que les facilitateurs peuvent être mis à profit pour accroître l'utilization des inhibiteurs de SGLT2. Les efforts déployés pour aborder et optimiser ces obstacles et ces facilitateurs dans le cadre d'une approche systématique pourraient mener à une augmentation de l'utilization de ces médicaments efficaces.

Digital health technologies to support medication adherence in chronic kidney disease.

Non-adherence to medications is a critical challenge in the management of people with chronic kidney disease (CKD). This review explores the complexities of adherence in this population, the unique barriers and enablers of good adherence behaviours, and the role of emerging digital health technologies in bridging the gap between evidence-based treatment plans and the real-world standard of care. We present the current evidence supporting the use of digital health interventions among CKD populations, identifying the key research questions that remain unanswered, and providing practical strategies for clinicians to support medication adherence in a digital age.

Cannabinoids for Symptom Management in Patients with Kidney Failure: A Narrative Review.

People with kidney failure can experience a range of symptoms that lead to suffering and poor quality of life. Available therapies are limited, and evidence for new treatment options is sparse, often resulting in incomplete relief of symptoms. There is growing interest in the potential for cannabinoids, including cannabidiol and tetrahydrocannabinol, to treat symptoms across a wide range of chronic diseases. As legal prohibitions are withdrawn or minimized in many jurisdictions, patients are increasingly able to access these agents. Cannabinoid receptors, CB1 and CB2, are widely expressed in the body, including within the nervous and immune systems, and exogenous cannabinoids can have anxiolytic, antiemetic, analgesic, and anti-inflammatory effects. Considering their known physiologic actions and successful studies in other patient populations, cannabinoids may be viewed as potential therapies for a variety of common symptoms affecting those with kidney failure, including pruritus, nausea, insomnia, chronic neuropathic pain, anorexia, and restless legs syndrome. In this review, we summarize the pharmacology and pharmacokinetics of cannabinoids, along with what is known about the use of cannabinoids for symptom relief in those with kidney disease, and the evidence available concerning their role in management of common symptoms. Presently, although these agents show varying efficacy with a reasonable safety profile in other patient populations, evidence-based prescribing of cannabinoids for people with symptomatic kidney failure is not possible. Given the symptom burden experienced by individuals with kidney failure, there is an urgent need to understand the tolerability and safety of these agents in this population, which must ultimately be followed by robust, randomized controlled trials to determine if they are effective for symptom relief.

The effects of dipeptidyl peptidase-4 inhibitors on kidney outcomes.

AIMS: To summarize evidence from randomized controlled trials (RCTs) concerning the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on kidney outcomes in patients with type 2 diabetes mellitus (T2DM). METHODS: The Medline, EMBASE and Cochrane databases were searched for RCTs comparing DPP-4 inhibitors with a placebo, active comparator or standard care, with at least 500 person-years follow-up in patients with T2DM and with reporting of kidney outcomes. Treatment effects were summarized using random-effects meta-analysis. RESULTS: Ten trials including 47 955 patients (mean estimated glomerular filtration rate [eGFR] 71 mL/min/1.73m2 , mean follow-up 10 762 patient-years per trial) were eligible for inclusion. DPP-4 inhibitors were compared with placebo (five trials), active comparator (three trials), and standard care (two trials). Overall, treatment with DPP-4 inhibitors was associated with a greater decline in eGFR than treatment with the comparators (weighted mean difference -1.12 mL/min/1.73m2 , 95% confidence interval [CI] -1.61, -0.62; high-certainty evidence). There were no detectable effects of DPP-4 inhibitors on rates of doubling serum creatinine (risk ratio [RR] 1.10, 95% CI 0.90, 1.34; high-certainty evidence), end-stage kidney disease (RR 0.97, 95% CI 0.77, 1.23; high-certainty evidence), death from kidney causes (RR 1.81, 95% CI 0.67, 4.93; low-certainty evidence), or all-cause mortality (RR 1.01, 95% CI 0.95, 1.09; high-certainty evidence). DPP-4 inhibitors significantly reduced the risks of the surrogate kidney outcome of new albuminuria (RR 0.88, 95% CI 0.8, 0.98; moderate-certainty evidence) and worsening albuminuria (RR 0.88, 95% CI 0.82, 0.94; moderate-certainty evidence). There was no difference in the safety outcome of acute kidney injury (RR 1.04, 95% CI 0.57, 1.87; high-certainty evidence). CONCLUSIONS: Dipeptidyl peptidase-4 inhibitors are associated with a greater decline in eGFR, despite reducing the development and progression of albuminuria, and have no clear effect on other key kidney outcomes.

A life-threatening case of pregnancy-related atypical Haemolytic uremic syndrome and successful treatment with Eculizumab.

BACKGROUND: Pregnancy-related Atypical Haemolytic Uremic Syndrome (P-aHUS) is a rare condition affecting genetically predisposed women during pregnancy. It is often difficult to diagnose and has a significant impact on maternal and foetal outcomes. It is characterised by microangiopathic haemolytic anaemia and kidney injury from thrombotic microangiopathy. CASE PRESENTATION: A 27-year-old female of Lebanese descent presented at 36 weeks' gestation with foetal death in-utero (FDIU) with placental abruption on a background of previously normal antenatal visits. She was coagulopathic and anaemic with anuric acute kidney injury, requiring emergency Caesarean section, intubation and dialysis. Her coagulopathy rapidly resolved, however, her anaemia and renal dysfunction persisted. A diagnosis of P-aHUS was made, and she was empirically treated with Eculizumab. Her ADAMTS13 level was normal, effectively excluding thrombotic thrombocytopenic purpura. Within 2 weeks of treatment her haematological parameters improved, and her renal function began to recover and within 2 months she became dialysis independent. CONCLUSION: This case highlights the challenges of a timely diagnosis of P-aHUS from other pregnancy-related diseases. Although our patient is dialysis-independent, her risk of relapse remains high with subsequent pregnancies. Currently we are awaiting her genetic sequencing to complete her assessment for underlying mutations and are determining the safest approach to a future planned pregnancy.