Geographic variation in sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide-1 receptor agonist use in people with type 2 diabetes in New South Wales, Australia.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and cardio-renal outcomes for people with type 2 diabetes (T2D). However, geographic and socio-economic variation in use is not well understood. METHODS: We identified 367 829 New South Wales residents aged ≥40 years who dispensed metformin in 2020 as a proxy for T2D. We estimated the prevalence of use of other glucose-lowering medicines among people with T2D and the prevalence of SGLT2i and GLP-1RA use among people using concomitant T2D therapy (i.e. metformin + another glucose-lowering medicine). We measured the prevalence by small-level geography, stratified by age group, and characterized by remoteness and socio-economic status. RESULTS: The prevalence of SGLT2i (29.7%) and GLP-1RA (8.3%) use in people with T2D aged 40-64 increased with geographic remoteness and in areas of greater socio-economic disadvantage, similar to other glucose-lowering medicines. The prevalence of SGLT2i (55.4%) and GLP-1RA (15.4%) among people using concomitant T2D therapy varied across geographic areas, with lower SGLT2i use in more disadvantaged areas and localized areas of high GLP-1RA use (2.5 times the median). Compared with people aged 40-64 years, the prevalence of SGLT2i and GLP-1RA use was lower in older age groups, but with similar patterns of variation across geographic areas. CONCLUSIONS: The prevalence of SGLT2i and GLP-1RA use varied by geography, probably reflecting a combination of system- and prescriber-level factors. Socio-economic variation in GLP-1RA use was overshadowed by localized patterns of prescribing. Continued monitoring of variation can help shape interventions to optimize use among people who would benefit the most.

'We are somehow fixated on this being a diabetes drug': a qualitative study exploring the views of cardiologists and nephrologists about sodium-glucose cotransporter 2 inhibitor initiation.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are now indicated for heart failure and chronic kidney disease (CKD), irrespective of the presence of diabetes. Hence, cardiologists and nephrologists have an important role in initiating these drugs. AIMS: To explore cardiologists' and nephrologists' perspectives regarding initiating SGLT2i and their safety monitoring practices when initiating SGLT2i. METHODS: Purposive and snowball approaches were used to recruit participants working in diverse areas in New South Wales, Australia. Semi-structured interviews were conducted with 12 cardiologists and 12 nephrologists. Interviews were conducted until thematic saturation was reached. Emergent themes were identified from transcripts. An iterative general inductive approach was used for data analysis. RESULTS: There was a reluctance amongst most non-heart-failure subspecialist cardiologists to initiate SGLT2i. Reasons included the perception of SGLT2i as diabetes drugs, concern about side effects, lack of experience and issues with follow-up. In contrast, nephrologists reported feeling confident to initiate SGLT2i. Nephrologists varied in their opinions about the severity of CKD at which SGLT2i initiation was reasonable and monitoring of renal function following initiation. Government subsidisation was an important factor in the decision to prescribe SGLT2i to people without diabetes. CONCLUSIONS: Our findings highlight the complex transition from the perception of SGLT2i as diabetes drugs to cardiometabolic and reno-protective agents. Interdisciplinary collaboration may enable greater confidence amongst specialists to initiate SGLT2i, including in patients with CKD. Additionally, there is a need for clear and detailed guidance about SGLT2i prescription in patients with renal dysfunction and renal function monitoring following SGLT2i initiation.

Glucagon-like peptide-1 receptor agonists: a narrative review of clinical pharmacology and implications for peri-operative practice.

BACKGROUND: Glucagon-like peptide-1 receptor agonists are used increasingly in the management of patients living with type 2 diabetes mellitus and obesity. In patients using glucagon-like peptide-1 receptor agonists, a key concern in the peri-operative period is the increased risk of pulmonary aspiration due to delayed gastric emptying. This review provides an overview of the pharmacodynamic and pharmacokinetic properties of glucagon-like peptide-1 receptor agonists and the risk of delayed gastric emptying and aspiration. METHODS: We conducted searches of MEDLINE and EMBASE databases of articles published before January 2024 using the keywords and medical subject headings: incretins; glucagon-like peptide-1; GLP-1; glucagon-like peptide-1 receptor agonists; GLP-1 RA; peri-operative period; perioperative; peri-operative; stomach emptying; gastric emptying; pulmonary aspiration; aspiration; food regurgitation; and regurgitation. The evidence was analysed, synthesised and reported narratively. RESULTS: A total of 1213 articles were located after duplicates were removed. Two authors screened the titles and abstracts to identify those studies which assessed specifically the risk of delayed gastric emptying and pulmonary aspiration or regurgitation in the peri-operative period. We searched manually the reference lists of relevant studies to identify any additional case reports. Ten studies were identified. Available evidence was limited to case reports, case series and observational work. CONCLUSIONS: There is insufficient evidence to put forward definitive guidance regarding the ideal cessation period for glucagon-like peptide-1 receptor agonists before elective surgery. Precautionary practice is required until more evidence becomes available. We suggest an individualised, evidence-based approach. In patients living with type 2 diabetes mellitus, there is concern that prolonged cessation before surgery will have a detrimental effect on peri-operative glycaemic control and discussion with an endocrinologist is advised. For patients taking glucagon-like peptide-1 receptor agonists for weight management, these drugs should be withheld for at least three half-lives before an elective surgical procedure.

Sodium-glucose co-transporter 2 inhibitor therapy: use in chronic kidney disease and adjunctive sodium restriction.

The global burden of chronic kidney disease (CKD) has increased significantly over the past few decades. This reflects the rising prevalence of type 2 diabetes mellitus (T2DM) and hypertension, two leading causes of CKD. Hypertension, which can also be a complication of CKD, accelerates renal disease progression and augments cardiovascular risk, especially in individuals with diabetic kidney disease. Hence, blood pressure (BP) reduction is a vital component of CKD management. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a relatively novel class of medications developed to treat T2DM by inducing glycosuria and hence, lowering glycaemia. Additionally, SGLT2 inhibitors are antihypertensive, renoprotective and cardioprotective, even in individuals without T2DM, making them effective therapeutic agents for CKD. Another therapy that has proven to be antihypertensive, renoprotective and cardioprotective is dietary sodium restriction. This review evaluates the potential combined benefits of SGLT2 inhibition and dietary sodium restriction on the BP and renal parameters of individuals with CKD.

Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes-cardiovascular and renal benefits in patients with chronic kidney disease.

PURPOSE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have important cardiovascular and renal benefits in adults with type 2 diabetes who have or are at high risk of cardiovascular and renal disease. These benefits are seen in patients with impaired renal function where the glucose-lowering effects are not observed. Here, we review the pharmacokinetics and pharmacology of SGLT2 inhibitors in relation to cardiovascular and renal outcomes in patients with chronic kidney disease (CKD). METHODS: We searched PubMed and EMBASE for original research, meta-analyses and review articles relevant to the pharmacokinetics, and cardiac and renal outcomes of SGLT2 inhibitors published up until June 2019. Specialist society guidelines and publications were also consulted. RESULTS: Renal impairment is currently a contraindication to SGLT2 inhibitor use largely due to limited anti-hyperglycaemic efficacy. However, in cardiovascular outcome trials, and a dedicated renal outcome trial, cardiovascular and renal benefits were seen in participants with CKD suggesting that mechanisms underlying the cardiovascular and renal benefits of SGLT2 inhibitors are likely largely independent of the glucose-lowering action of these agents. CONCLUSIONS: Despite minimal glycaemic benefits in patients with type 2 diabetes and stage 3 CKD, the cardiovascular and renal benefits of these agents are preserved in this group of patients. Whether these agents have cardiovascular and renal benefits in patients with stage 4 CKD and patients with non-diabetic CKD needs further research.

Use of NSAIDs for osteoarthritis amongst older-aged primary care patients: engagement with information and perceptions of risk.

BACKGROUND: non-steroidal anti-inflammatory drugs (NSAIDs) are used commonly to treat osteoarthritis in older patients. OBJECTIVE: to explore the understandings of risk that older-aged primary care patients have in the context of the use of oral NSAIDs to treat osteoarthritis. METHOD: semi-structured interviews were conducted with 15 patients who were recruited from four general practices located in Sydney, Australia. Patients were aged at least 65 years and were currently taking, or in the past 2 years had taken, an NSAID for osteoarthritis. Emergent themes were identified from the transcripts and were compared within and across transcripts to develop more abstract concepts. RESULTS: patients demonstrated three key 'modes of disengagement' from medication-specific risk information, each of which could also be a mode of modulating a sense of danger and each of which would demand a unique clinical response. These were: 'transference of responsibility'-transferring the responsibility to their GP, 'general versus specific risk'-considering the risk of taking medicine in general as opposed to the specific risk of taking an NSAID, and 'personal immunity'-some patients with a long history of NSAID use without apparent toxicity believed they were, therefore, not at risk of future adverse effects, while a few patients believed they were immune to adverse effects of drugs in general. CONCLUSION: there is a need for greater recognition of these 'modes of disengagement'/'hazard modulation' in order to attain a clinical response leading to safer, more effective and more ethical use of medicines.

Prescribing of SGLT2 inhibitors in primary care: A qualitative study of General Practitioners and Endocrinologists.

AIMS: To explore: 1) General Practitioners' (GPs') perspectives regarding initiating SGLT2 inhibitors and the resources that inform their pharmacotherapy choices; and 2) The support provided to GPs by Endocrinologists in relation to the prescription of type 2 diabetes medications. METHODS: Semi-structured interviews with 15 GPs and 12 Endocrinologists working in diverse areas in New South Wales, Australia. Interviews were recorded, transcribed, and emergent themes were identified using a general inductive approach. RESULTS: Under-appreciation of the cardio-renal benefits of SGLT2 inhibitors, a preference for an Endocrinologist to initiate therapy, and patients' experiences with adverse effects were identified as reasons for low rates of initiating SGLT2 inhibitors by some GPs. GPs reported that they would like to receive education about this topic from Endocrinologists, ideally via case-based discussions. A perceived challenge faced by Endocrinologists in providing GP education included potential constraints on talk content imposed by industry at sponsored events. Endocrinologists indicated that interactive sessions were most useful to GPs. CONCLUSIONS: Despite the evidence for the cardio-renal benefits of SGLT2 inhibitors, there are barriers to GPs prescribing these agents. Case-based discussions between GPs and Endocrinologists about type 2 diabetes treatment including the role of SGLT2 inhibitors could overcome some of these barriers.

Potential Safety Issues with Use of Sodium-Glucose Cotransporter 2 Inhibitors, Particularly in People with Type 2 Diabetes and Chronic Kidney Disease.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a major advance in the fields of diabetology, nephrology, and cardiology. The cardiovascular and renal benefits of SGLT2 inhibitors are likely largely independent of their glycaemic effects, and this understanding is central to the use of these agents in the high-risk population of people with type 2 diabetes and chronic kidney disease. There are a number of potential safety issues associated with the use of SGLT2 inhibitors. These include the rare but serious risks of diabetic ketoacidosis and necrotising fasciitis of the perineum. The data regarding a possibly increased risk of lower limb amputation and fracture with SGLT2 inhibitor therapy are conflicting. This article aims to explore the potential safety issues associated with the use of SGLT2 inhibitors, with a particular focus on the safety of these drugs in people with type 2 diabetes and chronic kidney disease. We discuss strategies that clinicians can implement to minimise the risk of adverse effects including diabetic ketoacidosis and volume depletion. Risk mitigation strategies with respect to SGLT2 inhibitor-associated diabetic ketoacidosis are of particular importance during the current coronavirus disease 2019 (COVID-19) pandemic.

Combination Therapy with an SGLT2 Inhibitor as Initial Treatment for Type 2 Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND: Guidelines differ with regard to indications for initial combination pharmacotherapy for type 2 diabetes. AIMS: To compare the efficacy and safety of (i) sodium-glucose cotransporter 2 (SGLT2) inhibitor combination therapy in treatment-naïve type 2 diabetes adults; (ii) initial high and low dose SGLT2 inhibitor combination therapy. METHODS: PubMed, Embase and Cochrane Library were searched for randomised controlled trials (RCTs) of initial SGLT2 combination therapy. Mean difference (MD) for changes from baseline (HbA1c, weight, blood pressure) after 24⁻26 weeks of treatment and relative risks (RR, safety) were calculated using a random-effects model. Risk of bias and quality of evidence was assessed. RESULTS: In 4 RCTs (n = 3749) there was moderate quality evidence that SGLT2 inhibitor/metformin combination therapy resulted in a greater reduction in HbA1c (MD (95% CI); -0.55% (-0.67, -0.43)) and weight (-2.00 kg (-2.34, -1.66)) compared with metformin monotherapy, and a greater reduction in HbA1c (-0.59% (-0.72, -0.46)) and weight (-0.57 kg (-0.89, -0.25)) compared with SGLT2 inhibitor monotherapy. The high dose SGLT2 inhibitor/metformin combination resulted in a similar HbA1c but greater weight reduction; -0.47 kg (-0.88, -0.06) than the low dose combination therapy. The RR of genital infection with combination therapy was 2.22 (95% CI 1.33, 3.72) and 0.69 (95% CI 0.50, 0.96) compared with metformin and SGLT2 inhibitor monotherapy, respectively. The RR of diarrhoea was 2.23 (95% CI 1.46, 3.40) with combination therapy compared with SGLT2 inhibitor monotherapy. CONCLUSIONS: Initial SGLT2 inhibitor/metformin combination therapy has glycaemic and weight benefits compared with either agent alone and appears relatively safe. High dose SGLT2 inhibitor/metformin combination therapy appears to have modest weight, but no glycaemic benefits compared with the low dose combination therapy.

"It looks after me": how older patients make decisions about analgesics for osteoarthritis.

OBJECTIVE: To explore the key motivators behind selection of analgesics (nonsteroidal antiinflammatory drugs [NSAIDs], acetaminophen, and complementary medications [CMs]) by patients with osteoarthritis (OA). METHODS: We performed a qualitative study in which in-depth semistructured interviews were conducted with 15 OA patients recruited from 4 general practices in Sydney, Australia. Patients were ages ≥65 years, and were currently taking or had recently taken an NSAID for OA. RESULTS: Three key themes emerged from the data: reliance, routine, and pill load. Patients were strongly reliant upon NSAIDs because they consistently satisfied their needs. By contrast, they were much less reliant upon acetaminophen because of uncertainty or skepticism about its effectiveness. They were not reliant upon CMs but were willing to take them indefinitely because they were perceived as being without risk. Many patients took an NSAID as well as CMs as part of a "daily routine." By contrast, patients had difficulty developing a routine around using acetaminophen at the recommended maximum dose because of the implicit frequency of dosing required and an aversion to the associated "pill load." CONCLUSION: The results highlight the importance of exploring the perceptions and preferences of patients with regard to analgesics for OA. Clinician advice regarding analgesia for OA should take account of the possible reliance of the patient upon an NSAID, their medicine routines, and their potential concern about the pill load associated, in particular, with acetaminophen.