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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. [ABSTRACT FROM AUTHOR]

Background: Medication use in pregnancy is common; however, it is unknown if clinical practice guideline (CPG) prescribing recommendations referred to in Australia at the state, national and international level are consistent. Aims: This systematic review aimed to: (1) identify sources of CPGs that inform prescribing during pregnancy in Australia; (2) assess CPG quality; and (3) evaluate variation within CPG recommendations for medication use in three common conditions in pregnancy: prophylactic antibiotics following premature rupture of membranes (PROM) at term, antidepressants in pregnancy and metformin in gestational diabetes mellitus (GDM). Materials and Methods: A literature search was conducted across PubMed, Scopus and EMBASE databases. Grey literature was identified through publicly available Australian policy statements. Prescribing recommendations for prophylactic antibiotics following PROM at term, antidepressants in pregnancy and metformin in GDM, were compared at the state, national and international levels. CPG quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Results: We identified 39 CPG sources that inform prescribing during pregnancy in Australia. CPG quality varied between resources. There was minor variation in recommendations for antibiotic prophylaxis in PROM at term. Recommendations regarding metformin use in GDM were also variable, with CPGs either recommending its use as a first‐line agent when lifestyle modifications are not effective or when insulin therapy is not practicable. Recommendations for antidepressant use were consistent across CPGs analysed. Conclusion: Multiple CPGs exist to inform prescribing during pregnancy in Australia, with variation present within CPG quality and recommendations. These findings offer insight into potential sources of variation in maternal and neonatal health outcomes. [ABSTRACT FROM AUTHOR]

Background: Many people living with type 1 diabetes (type 1 diabetes mellitus (T1DM)) do not meet glycaemic targets. Adjunctive therapies have both risks and metabolic benefits and may have a role in selected patients. Aim: To review the prescribing patterns of adjunctive therapy for the treatment of T1DM diabetes in Australia. Methods: We conducted an online survey of Australian endocrinologists and endocrinology registrars. We surveyed the frequency of, motivations and concerns regarding the prescription of metformin, dipeptidyl peptidase‐4 (DPP‐IV) inhibitors, sodium‐glucose transport protein 2 (SGLT‐2) inhibitors and glucagon‐like peptide 1 receptor agonist (GLP1RA) in T1DM. Results: Fifty‐two practitioners participated. Most respondents (94%) had prescribed adjuncts for the treatment of T1DM in some form. Weight (89%), large insulin doses (73%), glycaemic variability (52%), high HbA1c (48%) and the presence of cardiovascular disease (48%) were the most common factors determining the use of adjuncts. The most commonly prescribed adjuncts were metformin (94%) and SGLT‐2 inhibitors (65%). Respondents who had never prescribed an SGLT‐2 inhibitor (n = 18) reported risk of diabetic ketoacidosis (DKA) (100%), off‐label status (39%), lack of evidence (39%), withdrawal of support from the European Medicines Agency (17%) and cost (17%) as factors contributing to their decision. Thirty‐one respondents (60%) had prescribed a GLP1RA. Among those who had never prescribed a GLP1RA (n = 21), off‐label status (57%), lack of evidence (48%), cost (38%) and expected lack of efficacy (14%) were factors affecting their decision. Only five respondents (10%) had prescribed a DPP‐IV inhibitor. Conclusion: Australian endocrinologists commonly prescribe adjuncts to address cardiometabolic concerns in T1DM. DKA risk and off‐label status are significant factors contributing to reluctance to prescribe. [ABSTRACT FROM AUTHOR]

Background: There are limited data relating to the effects of metformin‐associated vitamin B12 deficiency on the risk of distal symmetrical polyneuropathy (DSPN) and megaloblastic anaemia in well‐characterised community‐based cohorts. Aims: To assess inter‐relationships between metformin therapy, vitamin B12 deficiency assessed using serum active B12 concentrations, and DSPN and anaemia in 1492 Fremantle Diabetes Study Phase 2 (FDS2) participants with type 2 diabetes. Methods: Prevalence rates of vitamin B12 deficiency (total <80 pmol/L, active <23 pmol/L) and borderline deficiency (total ≥80 and ≤200 pmol/L, active ≥23 and ≤35 pmol/L) were determined using baseline sera. The relationship between vitamin B12 status and both DSPN and anaemia was assessed using multivariable analyses. Results: Most FDS2 participants (94.4%) were vitamin B12 replete (total serum concentration >200 pmol/L, active >35 pmol/L), 2.0% were deficient (total <80 pmol/L, active <23 pmol/L) and the remainder (3.6%) borderline. Although metformin treatment increased the odds of deficiency (4.2%, 3.1% borderline) in a dose‐dependent fashion (odds ratio (95% confidence interval) 39.4 (4.90–316) for >2000 mg daily compared with no treatment; P < 0.001), there was no significant association between vitamin B12 status and DSPN, anaemia (haemoglobin ≤130 g/L males, ≤120 g/L females), haemoglobin concentration or mean corpuscular volume (P ≥ 0.147). Metformin increased the likelihood of anaemia, especially at high doses, independent of vitamin B12 deficiency. Conclusions: Since nutritional sources likely attenuate metformin‐associated vitamin B12 malabsorption and its clinical sequelae in developed countries such as Australia, there is no need for routine/opportunistic serum vitamin B12 screening in metformin‐treated patients. [ABSTRACT FROM AUTHOR]

Background: Safe and appropriate use of medicines is essential to improve health outcomes in cirrhosis. However, little is known about the number and type of medicines dispensed to people with cirrhosis in Australia, as this predominantly occurs in the community. We aimed to characterise the prescriptions dispensed to people with cirrhosis and explore changes in the use of medication groups over time. Methods: Pharmaceutical Benefits Scheme data between 1 January 2016 and 30 June 2020 was extracted for consenting CirCare participants (multi-site, prospective, observational study). Prescriptions dispensed from cirrhosis diagnosis until liver transplant or death were included. Safety classifications for dispensed medicines were defined using published evidence-based recommendations. The pattern of medication use was analysed in 6-monthly time intervals. Generalised estimating equations models were used to estimate the change in consumption of medicines over time. Results: Five hundred twenty-two patients (mean age 60 years, 70% male, 34% decompensated at recruitment) were dispensed 89,615 prescriptions during the follow-up period, representing a median of 136 [interquartile range (IQR) 62–237] prescriptions and a median of 16 (IQR 11–23) unique medicines per patient (total n = 9306 medicines). The most commonly used medicines were proton pump inhibitors (PPIs) (dispensed at least once to 73% of patients), opioids (68%) and antibiotics (89%). Polypharmacy was prevalent, with 59–69% of observed participants in each time period dispensed five or more unique medicines. Prescription medication use increased over time (p < 0.001) independently of age, comorbidity burden and liver disease aetiology. The likelihood of taking PPIs, opioids, antidepressants and inhaled medicines also increased with each successive time period. Use of angiotensin therapies, metformin and statins differed over time between patients with compensated versus decompensated cirrhosis. General practitioners prescribed 69% of dispensed medicines, including a higher proportion of 'unsafe' and 'safety unknown' medicines compared with consultants/specialists (p < 0.001). Conclusions: Polypharmacy is common in people with cirrhosis and some medication groups may be overused. Pharmacovigilance is required and future medication safety efforts should target high-risk prescribing practices and promote medication rationalisation in the community. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes (T2D) is a well‐recognised cardiovascular disease (CVD) risk factor, and recent guidelines for the management of T2D include consideration of CVD risk. Aim: To assess whether contemporary clinical management of Australians with T2D is in accord with recent national and international guidelines. Methods: This Australia‐specific analysis of the CAPTURE study, a non‐interventional, cross‐sectional study included adults diagnosed with T2D ≥180 days prior to providing informed consent and visiting primary or specialist care. Main outcome measures were the use of blood glucose‐lowering medications (BGLMs), BGLMs with proven cardiovascular benefits and other CVD medications, stratified by CVD status and care setting. Results: Of 824 Australian participants in the CAPTURE sample, 332 (40.3%) had CVD. Oral BGLMs were used by 83.9% of all participants, most commonly metformin (76.0%), dipeptidyl peptidase‐4 inhibitors (28.8%), sodium‐glucose cotransporter‐2 inhibitors (SGLT2is; 21.8%) and sulfonylureas (21.7%). Insulin was used by 29.2% of participants. BGLMs with proven CV benefit were used by 22.6%; glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) were less commonly used than SGLT2is in all CVD groups, but these drug classes were more often prescribed in specialist than primary care (SGLT2is 25.4 vs 20.7%, GLP‐1 RAs 3.2 vs 0.8% respectively). Use of non‐BGLMs for CVD risk reduction appeared consistent with guidelines. Conclusions: Use of BGLMs with CVD benefits appears low in Australia, irrespective of CVD status. This likely reflects the delay in translation of clinical evidence into contemporary care and prescribing restrictions. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes is more prevalent among Aboriginal and Torres Strait Islander Peoples, especially those living in rural than urban areas. However, little is known about how diabetes is managed in different settings. Objective: To investigate differences in the prevalence of diabetes and the prescription of antidiabetic medications for Aboriginal and/or Torres Strait Islander Peoples living in urban or rural Australia. Design: Cross‐sectional study using de‐identified electronic medical records of 29,429 Aboriginal and/or Torres Strait Islander adults (60.4% females; mean age 45.2 ± 17.3 years) regularly attending 528 'mainstream' Australian general practices (MedicineInsight) in 2018. Findings: The prevalence of diabetes was 16.0%, and it was more frequent among those living in rural areas (22.0; 95% CI 19.3–24.4) than inner regional (17.6%; 95% CI 16.0–19.2) or major cities (15.8%; 95% CI 14.7–17.0; p < 0.001). The highest prevalence of diabetes was for males living in rural settings (25.0%). Of those with diabetes, 71.6% (95% CI 69.0–74.0) were prescribed antidiabetics, with a similar frequency in urban and rural areas (p = 0.291). After adjustment for sociodemographics, the only difference in diabetes management was a higher prescription of sulfonylureas in rural areas than in major cities (OR 1.39; 1.07–1.80). Discussion: The prevalence of diabetes was similar to other national data, although we found it was more frequent amongst Aboriginal and/or Torres Strait Islander males, especially those from rural areas. Conclusion: Despite current recommendations, one‐in‐four Indigenous Australians with diabetes were not prescribed antidiabetics. The clinical significance of more frequent prescriptions of sulfonylureas in rural locations remains unclear. [ABSTRACT FROM AUTHOR]

Aims: To estimate the effectiveness of metformin on glycaemic parameters among participants with incident prediabetes attending Australian general practices. Methods: This retrospective cohort study used electronic health records of regular participants (3+ visits in two consecutive years) attending 383 Australian general practices (MedicineInsight). Participants with 'incident' prediabetes (newly recorded diagnosis between 2012 and 2017) and their glycaemic parameters (haemoglobin A1c [HbA1c] or fasting blood glucose [FBG]) at 6‐, 12‐, and 18–24 months post diagnosis (unexposed) or post‐management with metformin (treatment) were identified from the database. We estimated the average treatment effect (ATE) of metformin management on glycaemic parameters using both linear regression and augmented inverse probability weighting. Results: Of the 4770 investigated participants with 'incident' prediabetes, 10.2% were managed with metformin. Participants on metformin had higher HbA1c levels at the baseline than those unexposed (mean 45 mmol/mol [6.2%] and 41 mmol/mol [5.9%], respectively), but no differences were observed at 6–12 months (mmol/mol ATE 0.0, 95% CI −0.4; 0.7) or 12–18 months (ATE −0.3, 95% CI −1.2; 0.3). However, participants on metformin had lower mean HbA1c mmol/mol at 18–24 months (ATE −1.1, 95% CI −2.0; 0.1) than those unexposed. Consistent results were observed for FBG (ATE at 6–12 months −0.14 [95% CI −0.25; −0.04], 12–18 months 0.02 [95% CI −0.08; 0.13] and 18–24 months −0.07 [95% CI −0.25; 0.12]). Conclusion: The higher HbA1c and FBG baseline levels among participants with 'incident' prediabetes managed with metformin improved after 6–12 months of starting pharmacological management, and the effect persisted for up to 24 months. Management with metformin could prevent further deterioration of glycaemic levels. [ABSTRACT FROM AUTHOR]

Background: The prevalence of gestational diabetes mellitus (GDM) has been increasing in Australia and worldwide. The study aims were to examine, in comparison with dietary intervention, perinatal outcomes for women with gestational diabetes who were attending a single hospital clinic and to identify predictors for their pharmacological GDM treatment. Methods: A prospective, observational study of women with GDM, treated with "Diet, N= 50", "Metformin, N = 35", "Metformin and Insulin, N = 46" or "Insulin, N = 20". Findings: The mean BMI for the whole cohort was 25.8 ± 4.7 kg/m². The Metformin group, compared to the Diet group, had OR=3.1 (95% CI:1.13 to 8.25) for caesarean section birth (LSCS) compared to normal vaginal birth mode with no longer such a significant association after controlling for the number of their elective LSCS. The insulin treated group had the highest number of small for gestational age neonates (20%, p<0.05) with neonatal hypoglycaemia (25%, p< 0.05). Fasting glucose value on oral GTT (glucose tolerance test) was the strongest predictor for a pharmacological intervention requirement with OR = 2.77 (95CI%: 1.16 to 6.61), followed by timing of OGTT with OR=0.90 (95% CI: 0.83 to 0.97) and previous pregnancy loss with OR=0.28 (95% CI:0.10 to 0.74). Interpretation: These data suggest that metformin may be a safe alternative treatment to insulin treatment in GDM. Raised fasting glucose on oral GTT was the strongest indicator that GDM women with BMI < 35 kg/m² may require pharmacological therapy. Further studies are needed to identify the most effective and safe management of gestational diabetes within the public hospital setting. [ABSTRACT FROM AUTHOR]

Introduction: Primary care provides an opportunity to prevent community acquired, medicine or drug-induced acute kidney injury. One of the barriers to proactive prevention of medicine-induced kidney injury in primary care is the lack of a list of nephrotoxic medicines that are most problematic in primary care, particularly one that provides a comparison of risks across medicines.Objective: The aim of this study was to consolidate evidence on the risks associated with medicines and acute kidney injury, with a focus on medicines used in primary care.Method: We searched the MEDLINE and EMBASE databases to identify published studies of all medicines associated with acute kidney injury identified from spontaneous report data. For each medicine positively associated with acute kidney injury, as identified from spontaneous reports, we implemented a sequence symmetry analysis (SSA) and a case-control design to determine the association between the medicine and hospital admission with a primary diagnosis of acute kidney injury (representing community-acquired acute kidney injury). Administrative claims data held by the Australian Government Department of Veterans' Affairs for the study period 2005-2019 were used.Results: We identified 89 medicines suspected of causing acute kidney injury based on spontaneous report data and a reporting odds ratio above 2, from Japan, France and the US. Spironolactone had risk estimates of 3 or more based on spontaneous reports, SSA and case-control methods, while furosemide and trimethoprim with sulfamethoxazole had risk estimates of 1.5 or more. Positive association with SSA and spontaneous reports, but not case control, showed zoledronic acid had risk estimates above 2, while candesartan telmisartan, simvastatin, naproxen and ibuprofen all had risk estimates in SSA between 1.5 and 2. Positive associations with case-control and spontaneous reports, but not SSA, were found for amphotericin B, omeprazole, metformin, amlodipine, ramipril, olmesartan, ciprofloxacin, valaciclovir, mycophenolate and diclofenac. All with the exception of metformin and omeprazole had risk estimates above 2.Conclusion: This research highlights a number of medicines that may contribute to acute injury; however, we had an insufficient sample to confirm associations of some medicines. Spironolactone, furosemide, and trimethoprim with sulfamethoxazole are medicines that, in particular, need to be used carefully and monitored closely in patients in the community at risk of acute kidney injury. [ABSTRACT FROM AUTHOR]

Aim: To assess the prevalence of metabolic syndrome in type 1 diabetes, and its age‐related association with diabetes complications. Methods: Australian National Diabetes Information Audit and Benchmarking (ANDIAB) was a well‐established quality audit programme. It provided cross‐sectional data on people attending specialist diabetes services across Australia. We determined the prevalence of metabolic syndrome (WHO criteria) in adults with type 1 diabetes and its associations with diabetes complications across age groups. Results: Metabolic syndrome prevalence was 30% in 2120 adults with type 1 diabetes. Prevalence increased with age: 21% in those aged <40 years, 35% in those aged 40–60 years, and 44% in those aged >60 years (P<0.001), which was driven by an increase in hypertension rate. Metabolic syndrome was associated with a higher prevalence of microvascular, macrovascular and foot complications, with the greatest impact at a younger age. The odds ratio for macrovascular complications with metabolic syndrome, compared with without, was 5.9 (95% CI 2.1–16.4) in people aged <40 years, 2.7 (95% CI 1.7–4.2) in those aged 40–60 years, and 1.7 (95% CI 1.1–2.7) in those aged >60 years (all P < 0.05). Metformin use was higher in those with metabolic syndrome (16% vs 4%; P<0.001). Conclusions: In this large Australian cohort, metabolic syndrome was common in type 1 diabetes and identified people at increased risk of the spectrum of diabetes complications, particularly in young to middle‐aged adults. Potential clinical implications are that therapies targeting insulin resistance in this high‐risk group may reduce diabetes complications and should be explored. [ABSTRACT FROM AUTHOR]

Purpose: Medicine dispensing data require extensive preparation when used for research and decisions during this process may lead to results that do not replicate between independent studies. We conducted an experiment to examine the impact of these decisions on results of a study measuring discontinuation, intensification, and switching in a cohort of patients initiating metformin., Methods: Four Australian sites independently developed a HARmonized Protocol template to Enhance Reproducibility (HARPER) protocol and executed their analyses using the Australian Pharmaceutical Benefits Scheme 10% sample dataset. Each site calculated cohort size and demographics and measured treatment events including discontinuation, switch to another diabetes medicine, and intensification (addition of another diabetes medicine). Time to event and hazard ratios for associations between cohort characteristics and each event were also calculated. Concordance was assessed by measuring deviations from the calculated median of each value across the sites., Results: Good agreement was found across sites for the number of initiators (median: 53 127, range: 51 848-55 273), gender (56.9% female, range: 56.8%-57.1%) and age group. Each site employed different methods for estimating days supply and used different operational definitions for the treatment events. Consequently, poor agreement was found for incidence of discontinuation (median 55%, range: 34%-67%), switching (median 3.5%, range: 1%-7%), intensification (median 8%, range: 5%-12%), time to event estimates and hazard ratios., Conclusions: Differences in analytical decisions when deriving exposure from dispensing data affect replicability. Detailed analytical protocols, such as HARPER, are critical for transparency of operational definitions and interpretations of key study parameters., (© 2024 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

This is the full version of the Australasian Diabetes in Pregnancy Society (ADIPS) 2020 guideline for pre‐existing diabetes and pregnancy. The guideline encompasses the management of women with pre‐existing type 1 diabetes and type 2 diabetes in relation to pregnancy, including preconception, antepartum, intrapartum and postpartum care. The management of women with monogenic diabetes or cystic fibrosis‐related diabetes in relation to pregnancy is also discussed. [ABSTRACT FROM AUTHOR]

Aim: To determine the patterns and predictors of pharmacological treatment initiation for type 2 diabetes and whether treatment initiation is consistent with Australian clinical practice guidelines that recommend metformin monotherapy. Methods: Individuals aged 40–99 years initiating a non‐insulin type 2 diabetes medication between July 2013 and February 2018 were identified from a 10% random national sample of pharmacy dispensing data. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the predictors of initiating sulfonylurea monotherapy, non‐guideline monotherapy and combination therapy compared with metformin monotherapy. Predictors included age, sex, initiation year and comorbidities determined using the Rx‐Risk comorbidity index. Results: Of the 47 860 initiators, [47% women, mean age 60.7 (sd 12.1) years], 85.8%, 4.6%, 1.9% and 7.7% received metformin monotherapy, sulfonylurea monotherapy, non‐guideline monotherapy and combination therapy, respectively. Increasing age was associated with increasing odds of initiating sulfonylurea monotherapy and non‐guideline monotherapy. Combination therapy initiation was less likely in women (OR 0.74, 95% CI 0.69–0.79) and people with more comorbidities (e.g. OR 0.36, 95% CI 0.29–0.44 for seven or more comorbidities vs. no comorbidities) but more likely in congestive heart failure (OR 1.42, 95% CI 1.22–1.65), cerebrovascular disease (OR 1.50, 95% CI 1.32–1.69) and dyslipidaemia (OR 1.29, 95% CI 1.19–1.40). Conclusion: Treatment initiation in Australia is largely consistent with clinical practice guidelines, with 86% of individuals initiating metformin monotherapy. Initiation on combination therapy was more common in men and in those with fewer comorbidities. What's new?: Metformin or sulfonylurea monotherapy are guideline‐recommended initial treatments for type 2 diabetes in Australia.Some 86% of Australians with type 2 diabetes received metformin monotherapy, 5% sulfonylurea monotherapy, 2% other monotherapy and 8% combination therapy as initial pharmacotherapy.Initial sulfonylurea monotherapy prescribing has become less frequent in recent years.People initiating combination therapy were more likely to be men and to have fewer comorbidities.Prescribing patterns for type 2 diabetes medications in Australia indicate a high level of concordance with clinical practice guidelines. [ABSTRACT FROM AUTHOR]

Background: Temporal changes in the dispensing of glucose-lowering drugs (GLD) and their associated costs among elderly populations is unclear. This information is especially relevant to countries in which medications are partly or fully government subsidized. Objective: Our objective was to estimate the trends in prevalence, incidence and costs associated with GLD dispensed to older Australians. Methods: We analysed Pharmaceutical Benefits Scheme data for 76,906 people aged ≥ 65 years dispensed diabetes medications over the period 2013–2016. Results: Older males were dispensed more GLD than were older females, with the marginal difference increasing from 3.2% in 2013 (age-sex adjusted incidence rate ratio [aIRR] 1.032; 95% confidence interval [CI] 1.024–1.041; p < 0.001) to 3.9% in 2016 (aIRR 1.039; 95% CI 1.030–1.047; p < 0.001). The number of GLD dispensed per person was consistently lower in those aged ≥ 75 years than in those aged 65–74 years, with the gap widening over the years. More patients were initiated with sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors over the study period, at the expense of older GLD. The proportion of users and attributed costs associated with the use of metformin, sulfonylureas, α-glucosidase inhibitors and thiazolidinediones decreased over time. The total subsidized costs of GLD is forecast to increase to $A395 million by 2020. Conclusions: The treatment landscape for diabetes in Australia is undergoing dynamic change. More patients were initiated with the newer but costlier GLD over the study period. [ABSTRACT FROM AUTHOR]

In the 1920s, guanidine, the active component of Galega officinalis, was shown to lower glucose levels and used to synthesize several antidiabetic compounds. Metformin (1,1 dimethylbiguanide) is the most well-known and currently the only marketed biguanide in the United States, United Kingdom, Canada, and Australia for the treatment of non-insulin-dependent diabetes mellitus. Although phenformin was removed from the US market in the 1970s, it is still available around the world and can be found in unregulated herbal supplements. Adverse events associated with therapeutic use of biguanides include gastrointestinal upset, vitamin Bi 2 deficiency, and hemolytic anemia. Although the incidence is low, metformin toxicity can lead to hyperlactatemia and metabolic acidosis. Since metformin is predominantly eliminated from the body by the kidneys, toxicity can occur when metformin accumulates due to poor clearance from renal insufficiency or in the overdose setting. The dominant source of metabolic acidosis associated with hyperlactatemia in metformin toxicity is the rapid cytosolic adenosine triphosphate (ATP) turnover when complex I is inhibited and oxidative phosphorylation cannot adequately recycle the vast quantity of H + from ATP hydrolysis. Although metabolic acidosis and hyperlactatemia are markers of metformin toxicity, the degree of hyperlactatemia and severity of acidemia have not been shown to be of prognostic value. Regardless of the etiology of toxicity, treatment should include supportive care and consideration for adjunct therapies such as gastrointestinal decontamination, glucose and insulin, alkalinization, extracorporeal techniques to reduce metformin body burden, and metabolic rescue. [ABSTRACT FROM AUTHOR]

Background: In Australia's Northern Territory, Indigenous mothers account for 33% of births and have high rates of hyperglycemia in pregnancy. The prevalence of type 2 diabetes (T2D) in pregnancy is up to 10‐fold higher in Indigenous than non‐Indigenous Australian mothers, and the use of metformin is common. We assessed birth outcomes in relation to metformin use during pregnancy from a clinical register. Methods: The study included women with gestational diabetes (GDM), newly diagnosed diabetes in pregnancy (DIP), or pre‐existing T2D from 2012 to 2016. Data were analyzed for metformin use in the third trimester. Regression models were adjusted for maternal age, body mass index, parity, and insulin use. Results: Of 1649 pregnancies, 814 (49.4%) were to Indigenous women, of whom 234 (28.7%) had T2D (vs 4.6% non‐Indigenous women; P < 0.001). Metformin use was high in Indigenous women (84%‐90% T2D, 42%‐48% GDM/DIP) and increased over time in non‐Indigenous women (43%‐100% T2D, 14%‐35% GDM/DIP). Among Indigenous women with GDM/DIP, there were no significant differences between groups with and without metformin in cesarean section (51% vs 39%; adjusted odds ratio [aOR] 1.25, 95% confidence interval [CI] 0.87‐1.81), large for gestational age (24% vs 13%; aOR 1.5, 95% CI 0.9‐2.5), or serious neonatal adverse events (9.4% vs 5.9%; aOR 1.32, 95% CI 0.68‐2.57). Metformin use was independently associated with earlier gestational age (37.7 vs 38.5 weeks), but the risk did not remain independently higher after exclusion of women managed with medical nutrition therapy alone, and the increase in births <37 weeks was not significant on multivariate analysis. Conclusions: We found no clear evidence of any adverse outcomes related to the use of metformin for the treatment of hyperglycemia in pregnancy. HighlightsBased on 5 years of real‐world clinical register data, we report that the use of metformin in pregnancy was high among Indigenous women and has increased from 2012 to 2016 among non‐Indigenous women with type 2 diabetes and gestational diabetes in a remote region of Australia.We found no clear evidence of any adverse outcomes related to the use of metformin for the treatment of hyperglycemia in pregnancy. [ABSTRACT FROM AUTHOR]

Aim: To assess the long‐term clinical benefits of early combination treatment with vildagliptin‐metformin vs. standard‐of‐care, metformin monotherapy in the ongoing VERIFY study. Methods: We randomized 2001 participants with multi‐ethnic background, aged 18–70 years, having HbA1c levels 48–58 mmol/mol (6.5–7.5%) and BMI 22–40 kg/m2. Baseline data included HbA1c, fasting plasma glucose and homeostasis model β‐cell and insulin sensitivity. Standardized meal‐tests, insulin secretion rate relative to glucose, and oral glucose insulin sensitivity were assessed in a subpopulation. Results: Out of 4524 screened, data were collected from the 2001 eligible participants (53% women) across Europe (52.4%), Latin America (26.8%), Asia (17.2%), South Africa (3.1%) and Australia (0.5%). The median (interquartile range) disease duration was 3.4 (0.9, 10.2) months; mean (±SD) age 54.3±9.4 years; weight 85.5±17.5 kg and BMI 31.1±4.7 kg/m2. Baseline HbA1c was 52±3 mmol/mol (6.9±0.3%), fasting plasma glucose 7.5±1.5 mmol/l and the median (interquartile range) of fasting insulin was 109 (75–160) mU/l. Homeostasis model β‐cell and insulin sensitivity values were 84% (60, 116) and 46% (31, 68), respectively. In those undertaking meal‐tests, insulin secretion rate relative to glucose was 28±12 pmol/min/m2/mmol/l and oral glucose insulin sensitivity was 353±57 ml/min/m2. Conclusions: Our current, multi‐ethnic, newly diagnosed VERIFY population reflects a characteristic presence of early insulin resistance in participants with increased demand for insulin associated with obesity. The VERIFY study will provide unique evidence in characterizing therapeutic intervention in a diverse population with hyperglycaemia, focusing on durability of early glycaemic control. What's new?: The VERIFY study is the first study to assess the long‐term clinical benefits of early combination treatment with a dipeptidyl peptidase‐4 inhibitor (vildagliptin)‐metformin vs. standard‐of‐care metformin monotherapy in people newly diagnosed with Type 2 diabetes.This report describes the baseline characteristics of a newly diagnosed population with Type 2 diabetes from a diverse geographical and ethnic background, demonstrating a classic profile of presence of early insulin resistance associated with elevated BMI as a surrogate for obesity.The study anticipates generating unique evidence on the progression of β‐cell function, insulin resistance, early complications of diabetes, and effect on health status upon treatment with early vildagliptin‐metformin combination. [ABSTRACT FROM AUTHOR]

Purpose: The management of type 2 diabetes mellitus (T2DM) is complex. The aim of this work is to explore factors that predict the need for add-on therapy in patients with T2DM in the community.Methods: We accessed longitudinal, pharmacy payment claim records from the national Pharmaceutical Benefits Scheme (PBS) (Subsidises costs of medicines: government pays difference between patient co-payments, lower in concessional patients, and additional cost of drug.) for the period January 2006 to September 2014 (EREC/MI3127) from a 10% random sample of the Australian population validated to be representative of the population by the Australian Bureau of Statistics (ABS). Likely, T2DM patients were identified as those having been dispensed a single anti-hyperglycaemic drug (monotherapy). The time taken and possible factors that might lead to the addition of a second therapy were examined. An examination was made of trends in the co-prescription of either antihypertensive or anti-hyperlipidaemic agents in relation to the time (± 3 years) of initiating an anti-hyperglycaemic agent.Results: Most (83%) presumed T2DM patients were initiated with metformin. The average time until the second agent was added was 4.8 years (95% CI 4.7-4.9). Satisfactory adherence, age, male gender, initiating therapy after 2012 and initiating with a sulphonylurea drug all were significant risks for add-on therapy. There was no overall trend in the initiation of antihypertensive and/or anti-hyperlipidaemic agents with respect to the time of anti-hyperglycaemic initiation.Conclusion: The usefulness of a longitudinal dataset of pharmacy-claim records is demonstrated. Over half of all older and socioeconmically disadvantaged T2DM patients captured in this longitudinal claims database will be prescribed a second anti-hyperglycaemic agent within 5 years of their first drug therapy. Several factors can predict the risk of prescription of add-on therapy, and these should be considered when prescribing medications to treat T2DM. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to (1) determine the trends in the utilisation of metformin in Australia, (2) determine the appropriateness of metformin dosing in an Australian teaching hospital and (3) gather the opinions of prescribers on the relationship between metformin dose and renal function. Methods: National prescription data between 1990 and 2012 were accessed. A retrospective audit (2008-2012) of metformin doses and patient renal function (20 % random sample of all in-patients prescribed metformin) was conducted at St Vincent's Hospital (SVH), Sydney. Prescribers of metformin were interviewed (semi-structured; consultants at SVH) or surveyed (Australian endocrinologists) to gather their understanding of metformin dosing in relation to renal function. Results: Metformin utilisation increased fivefold nationally between 1995 and 2012. Metformin tended to be under-dosed in SVH patients with normal renal function (83.5 %) and over-dosed in patients with impaired renal function (estimated glomerular filtration rate (eGFR) <30 mL/min, 50 %). Consultants indicated that metformin doses needed to be reduced in renal impairment. Most endocrinologists (61 %) were comfortable prescribing metformin down to eGFRs around 30 mL/min. Conclusion: The use of metformin increased greatly over the period of the study. Metformin is prescribed frequently for patients with eGFR values below the minimal level approved in the product label (60 mL/min). While prescribers expressed their understanding of the need to reduce metformin doses in patients with renal impairment, we found that metformin doses were higher than appropriate in patients with impaired renal function. Metformin may be used safely when renal function is poor provided dosage is appropriately reduced. [ABSTRACT FROM AUTHOR]

Objective. To examine the effect of diabetes treatment on change of measures of specific cognitive domains over 4 years. Research Design and Methods. The sample was drawn from a population-based cohort study in Australia (the PATH Through Life Study) and comprised 1814 individuals aged 65–69 years at first measurement, of whom 211 were diagnosed with diabetes. Cognitive function was measured using 10 neuropsychological tests. The effect of type of diabetes treatment (diet, oral hypoglycemic agents, and insulin) on measures of specific cognitive domains was assessed using Generalized Linear Models adjusted for age, sex, education, smoking, physical activity level, BMI, and hypertension. Results. Comparison of cognitive function between diabetes treatment groups showed no significant effect of type of pharmacological treatment on cognitive function compared to diet only group or no diabetes group. Of those on oral hypoglycaemic treatment only, participants who used metformin alone had better cognitive function at baseline for the domains of verbal learning, working memory, and executive function compared to participants on other forms of diabetic treatment. Conclusion. This study did not observe significant effect from type of pharmacological treatment for diabetes on cognitive function except that participants who only used metformin showed significant protective effect from metformin on domain of verbal learning, working memory, and executive function. [ABSTRACT FROM AUTHOR]

Unlabelled: Glucose lowering medication use among patients with type 2 diabetes and advanced renal disease (eGFR<60) in a large multinational outcome trial (TREAT) is assessed. We demonstrate statistically significant differences regionally in use of metformin at lower eGFR and increasing reliance upon insulin with/without other medications at low eGFR.Introduction: As renal disease advances, most of the oral anti-diabetic agents requiring renal clearance must be reduced or discontinued. The potential for prolonged hypoglycemia, fluid/volume overload and congestive heart failure may complicate medication choices. In order to evaluate patterns of glycemia management we describe glucose lowering medication use among patients with advanced renal disease and type 2 diabetes in a large multinational outcome trial designed to focus on patients with eGFR<60 in order to commence a dialog on best practices. We felt that analysis of this data would be able to describe regional variations in treatment within a multinational trial in order to understand potential outcome differences attributed to complications.Results: The patients entering this study had moderate glycemic control. Insulin therapy either alone (32%) or in combination with other agents (17%) reflected a shift towards insulin use in those subjects with decreased renal function when compared with standard populations with normal kidney function. The use of multiple oral agents, or oral agents plus insulin was quite common. While gender did not appear to play a role in medication choices, there were significant regional variations. For example, oral agents were used more in North America compared with other regions (Latin America, Australia/Western Europe, Russia/Eastern Europe). Patients enrolled at more advanced ages were less likely to be on a regimen of rapid-acting insulin alone consistent with recommendations that suggest a preference for longer-acting preparations in the geriatric population (1). Higher degrees of obesity were associated more complex treatment regimens. Despite this population being at high risk for cardiovascular events, the use of beta blockers (50%), statins (64%) and aspirin (48%) were relatively low, especially in the group that did not require medications to achieve adequate glycemic control.Conclusions: Current attempts to compare strategies for diabetes therapy must control for baseline demographic group differences influencing treatment choice. Future recommendations for glycemic control in patients with Grade 3 or higher chronic kidney disease require additional studies, with matched populations. We suggest that evaluation of studies similar to TREAT will assist in determining the optimal therapeutic regimens for populations with moderate to severe renal dysfunction, a condition in which repeated hospitalizations for fluid overload/heart failure add to the high cost of diabetes care. [ABSTRACT FROM AUTHOR]

Introduction: Metformin is a medication likely to improve measures of cardiometabolic disturbance in young people with mental illness. Evidence also suggests metformin may improve depressive symptoms. This 52-week double-blind randomised control trial (RCT) aims to investigate the efficacy of metformin pharmacotherapy as an adjunct to a healthy lifestyle behavioural intervention in improving cardiometabolic outcomes, and depressive, anxiety and psychotic symptoms in youth with clinically diagnosed major mood syndromes., Methods and Analysis: At least 266 young people aged 16-25 presenting for mental healthcare for major mood syndromes who are also at risk for poor cardiometabolic outcomes will be invited to participate in this study. All participants will engage in a 12-week sleep-wake, activity and metabolically focused behavioural intervention programme. As an adjunctive intervention, participants will receive either metformin (500-1000 mg) or placebo pharmacotherapy for 52 weeks.Participants will undergo a series of assessments including: (1) self-report and clinician-administered assessments; (2) blood tests; (3) anthropometric assessments (height, weight, waist circumference and blood pressure); and (4) actigraphy. Univariate and multivariate tests (generalised mixed-effects models) will be used to examine changes in primary and secondary outcomes (and associations with predetermined predictor variables)., Ethics and Dissemination: This study has been approved by the Sydney Local Health District Research Ethics and Governance Office (X22-0017). The results of this double-blind RCT will be disseminated into the scientific and broader community through peer-reviewed journals, conference presentations, social media and university websites., Trial Registration Number: Australian New Zealand Clinical Trials Registry (ANZCTR) Number: ACTRN12619001559101p, 12 November 2019., Competing Interests: Competing interests: Professor IBH was an inaugural Commissioner on Australia’s National Mental Health Commission (2012–2018). He is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates early-intervention youth services at Camperdown under contract to headspace. He is the Chief Scientific Advisor to, and a 5% equity shareholder in, InnoWell Pty LTd. InnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to deliver the $30M Australian Government-funded Project Synergy (2017–2020; a 3-year program for the transformation of mental health services) and to lead transformation of mental health services internationally through the use of innovative technologies. A/Prof EMS is Principal Research Fellow at the Brain and Mind Centre, The University of Sydney. She is Discipline Leader of Adult Mental Health, School of Medicine, University of Notre Dame, and a Consultant Psychiatrist. She was the Medical Director, Young Adult Mental Health Unit, St Vincent’s Hospital Darlinghurst until January 2021. She has received honoraria for educational seminars related to the clinical management of depressive disorders supported by Servier and Eli-Lilly pharmaceuticals. She has participated in a national advisory board for the antidepressant compound Pristiq, manufactured by Pfizer. She was the National Coordinator of an antidepressant trial sponsored by Servier., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Investigate efficacy and tolerability of intensifying diabetes treatment with once- or twice-daily biphasic insulin aspart 30 (BIAsp 30) added to sitagliptin, and twice-daily BIAsp 30 without sitagliptin in patients with type 2 diabetes (T2D) inadequately controlled on sitagliptin.Methods: Open-label, three-arm, 24-week trial; 582 insulin-naïve patients were randomized to twice-daily BIAsp 30+sitagliptin (BIAsp BID+Sit), once-daily BIAsp 30+sitagliptin (BIAsp QD+Sit) or twice-daily BIAsp 30 without sitagliptin (BIAsp BID), all with metformin.Results: After 24 weeks, HbA1c reduction (%) was superior with BIAsp BID+Sit vs. BIAsp QD+Sit (BIAsp BID+Sit minus BIAsp QD+Sit difference: -0.36 [95% CI -0.54; -0.17], P<0.001) and BIAsp BID (BIAsp BID minus BIAsp BID+Sit difference: 0.24 [0.06; 0.43], P=0.01). Observed final HbA1c values were 6.9%, 7.2% and 7.1% (baseline 8.4%), and 59.8%, 46.5% and 49.7% of patients achieved HbA1c <7.0%, respectively. Confirmed hypoglycaemia was lower with BIAsp QD+Sit vs. BIAsp BID (P=0.015); rate: 1.17 (BIAsp QD+Sit), 1.50 (BIAsp BID+Sit) and 2.24 (BIAsp BID) episodes/patient-year. Difference in bodyweight change favoured BIAsp QD+Sit vs. both BID groups (P<0.001).Conclusions: Adding BIAsp 30 to patients with T2D poorly controlled with sitagliptin and metformin is efficacious and well tolerated; however, while BIAsp BID+Sit showed superior glycaemic control, BIAsp QD+Sit had a lower rate of hypoglycaemia and showed no weight gain. [ABSTRACT FROM AUTHOR]

[Display omitted] Metformin is the most widely used drug to treat type 2 diabetes. Monitoring spatial patterns of metformin use could provide new insights into treatment of type 2 diabetes and the distribution among populations. This study applied a wastewater-based epidemiological (WBE) approach to estimate metformin use in different populations across Australia and compared these estimates with traditional approaches of surveys and prescription data. Twenty-four-hour influent samples were collected from 75 wastewater treatment plants (WWTPs) across Australia in 2016 and analysed for metformin. Metformin was detected in all samples ranging in concentration from 8.2 to 191 µg/L (median 58 µg/L). Concentrations were converted to population-weighted average consumption at the national level, resulting in an average consumption of 28.6 g/day/1000 people across Australia, which was within 7% of estimates from national prescription statistics. In addition, results for five out of seven states had an estimated prevalence of type 2 diabetes within 20% compared to the traditional epidemiology surveys. Spatial patterns were also observed between urban and rural settings, with higher consumption rates of metformin found in Major Cities (22.5 ± 10.9 g/d/1000 people) and Inner Regional cities (25.4 ± 13.4 g/d/1000 people) than in Outer Regional (17.0 ± 8.1 g/d/1000 people) and Remote areas (15.1 ± 7.4 g/d/1000 people). Consumption estimates were also correlated against socioeconomic factors of the specific catchment areas. Greater metformin use was correlated with populations of lower education and income levels, while positive correlations were found between metformin consumption and consumption of allopurinol, caffeine and venlafaxine. Our study provides more evidence on the distribution of metformin use across Australia, which can be used to develop public health strategies to reduce the overall burden of type 2 diabetes in specific regions. [ABSTRACT FROM AUTHOR]

The increasing global prevalence of gout and diabetes has led to a rise in the use of their respective medications, allopurinol and metformin. These are excreted via urine as oxypurinol and metformin and are discharged into wastewater and the environment. Current environmental monitoring of those two polar chemicals requires labour intensive and potentially inefficient sample pre-treatments, such as using solid-phase extraction or freeze-drying. This study validated a sensitive and simple method using direct-injection LC-MS/MS for the simultaneous measurement of oxypurinol and metformin in wastewater. The final method utilised a hydrophilic interaction liquid chromatography together with simple filtration through 0.2 μm regenerated cellulose filter followed by dilution in acetonitrile with a dilution factor of 10. The developed method was validated with the limit of quantifications (LOQ) of 0.11 and 0.34 μg/L for metformin and oxypurinol, respectively. The new method was applied to 42 influent wastewater samples and 6 effluent samples collected from 6 Australian wastewater treatment plants. Both compounds were detected well above the LOQ at concentrations 29-214 μg/L in influent and 2-53 μg/L in effluent for metformin, and 24-248 μg/L in influent and 4-81 μg/L in effluent for oxypurinol, demonstrating its high applicability., (© 2022 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

The article discusses the impact of a diabetes prevention program on labour force participation and personal income of Australians aged 45-64. It has been stated that the diabetes has been made a national health priority in Australia. It has been informed that introduction of either a lifestyle or metformin intervention program to prevent diabetes could result in improved health and wellbeing both in terms of additional working years and increased personal income.

The article provides information on a study which analyzed the impact of 2001 and 2005 National Prescribing Service (NPS) quality use of medicines (QUM) diabetes programs on the trends in metformin and insulin use among diabetes veterans in Australia. The utilization of change-in-level and change-in-trend terms to determine the impact of both programs on the use of metformin and insulin concurrent with oral hypoglycaemics is highlighted. It notes that over 55 percent of the diabetes population received metformin alone or in combination.

Background: This study assessed whether the number of comorbid conditions unrelated to diabetes was associated with a delay in therapeutic progression of diabetes treatment in Australian veterans. Methodology/Principal Findings: A retrospective cohort study was undertaken using data from the Australian Department of Veterans' Affairs (DVA) claims database between July 2000 and June 2008. The study included new users of metformin or sulfonylurea medicines. The outcome was the time to addition or switch to another antidiabetic treatment. The total number of comorbid conditions unrelated to diabetes was identified using the pharmaceutical-based comorbidity index, Rx-Risk-V. Competing risk regression analyses were conducted, with adjustments for a number of covariates that included age, gender, residential status, use of endocrinology service, number of hospitalisation episodes and adherence to diabetes medicines. Overall, 20134 veterans were included in the study. At one year, 23.5% of patients with diabetes had a second medicine added or had switched to another medicine, with 41.4% progressing by 4 years. The number of unrelated comorbidities was significantly associated with the time to addition of an antidiabetic medicine or switch to insulin (subhazard ratio [SHR] 0.87 [95% CI 0.84-0.91], P,0.001). Depression, cancer, chronic obstructive pulmonary disease, dementia, and Parkinson's disease were individually associated with a decreased likelihood of therapeutic progression. Age, residential status, number of hospitalisations and adherence to anti-diabetic medicines delayed therapeutic progression. Conclusions/Significance: Increasing numbers of unrelated conditions decreased the likelihood of therapeutic progression in veterans with diabetes. These results have implications for the development of quality measures, clinical guidelines and the construction of models of care for management of diabetes in elderly people with comorbidities. [ABSTRACT FROM AUTHOR]

The prevalence of gestational diabetes is increasing in Australia. Non-pharmacological intervention with dietary measures and exercise is the mainstay of therapy in most cases, but insulin is increasingly necessary to achieve adequate glycaemic control in some women. Basal-bolus insulin is the optimal management strategy, but therapy needs to be individualised. Although there is mounting evidence for the efficacy and safety of metformin, the lack of long-term follow-up data has prevented it from being recommended by most experts in the field. women with gestational diabetes need long-term follow-up because of their increased risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is the commonest cause of end-stage renal failure in both Australia and New Zealand. In addition, the burden of diabetes is prominent in those with chronic kidney disease who have not yet reached the requirement for renal replacement therapy. While diabetes is associated with a higher incidence of mortality and morbidity in all populations studied with kidney disease, little is known about optimal treatment strategies for hyperglycaemia and the effects of glycaemic treatment in this large group of patients. Metformin is recommended as the drug of first choice in patients diagnosed with type 2 diabetes in the USA, Europe and Australia. There are potential survival benefits associated with the use of metformin in additional to recent studies suggesting benefits in respect to cardiovascular outcomes and metabolic parameters. The use of metformin has been limited in patients with renal disease because of the perceived risk of lactic acidosis; however, it is likely that use of this drug would be beneficial in many with chronic kidney disease. Thus the potential benefits and harms of metformin are outlined in this review with suggestions for its clinical use in those with kidney disease. [ABSTRACT FROM AUTHOR]

The article offers information on treatment, evidence and consent of gestational diabetes. Topics include examines the importance of women with gestational diabetes mellitus (GDM) receiving up to date, balanced information on the risks and benefits of GDM management; and reports that it includes the use of metformin, the role of which remains under active debate, and weight management, where both insufficient and excess gestational weight gain may be harmful.

Background: Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms., Methods: MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35 mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500 mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05)., Discussion: Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design., Trial Registration: Australian Clinical Trials ACTRN12618001707257 . Registered on 16 October 2018., (© 2021. The Author(s).)

Background: Previous studies in general practice and hospital settings have identified that prescribing of non-insulin diabetes medications may be sub-optimal in people with type 2 diabetes (T2D) and renal impairment. Since these publications, a number of new medications have become available for the management of T2D. Study aims were to, in a cohort of Australians with T2D and renal impairment attending general practice, (1) investigate whether the prescribing of non-insulin diabetes medications is consistent with dosing adjustments recommended within current Australian Diabetes Society (ADS) guidelines; and (2) identify patient socio-demographic and clinical factors associated with at least one prescription of a non-insulin diabetes medication inconsistent with current ADS guidelines for medication doses. Methods: Cross-sectional study using data from the MedicineInsight general practice database managed by NPS MedicineWise. Patients with T2D who were aged 18 years and over, with an average eGFR< 60 ml/min/1.73m2 and at least one prescription of a non-insulin diabetes medication between 1st January 2015 and 30th June 2017 were included. Descriptive statistics were used to summarise patient characteristics and medication use. Marginal logistic regression models were used to estimate associations between sociodemographic and clinical factors and prescribing of ≥1non-insulin diabetes medicine not consistent with ADS guidelines. Results: The majority of the 3505 patients included (90.4%) had an average eGFR of 30-59 ml/min/1.73m2. In terms of absolute numbers, metformin was the medication most frequently prescribed at a dose not consistent with current ADS guidelines for dosing in renal impairment (n = 1601 patients), followed by DPP4 inhibitors (n = 611) and sulphonylureas (n = 278). The drug classes with the highest proportion of prescriptions with dosage not consistent with ADS guidelines were SGLT2 inhibitors (83%), followed by biguanides (58%) and DPP4 inhibitors (46%). Higher HbA1c, longer known diabetes duration and diagnosis of retinopathy were associated with receiving ≥1prescription with a dosage not consistent with guidelines. Conclusions: Prescribing of non-insulin diabetes medications at doses inconsistent with current ADS guideline recommendations for dosing adjustments for people with renal impairment was common. Further research is needed to understand how general practitioners access, interpret and apply the ADS guidelines and the impact this may have on patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Currently there is no drug therapy for abdominal aortic aneurysm (AAA) and most previous investigations have focused on imaging rather than clinical outcomes. The aim of this study was to assess whether AAA related clinical events were lower in patients prescribed metformin., Methods: This was a prospective cohort observational study performed in three cities in Australia, which was designed to study risk factors for clinical events not simply to focus on metformin. Patients with an asymptomatic unrepaired AAA of any diameter ≥30 mm were recruited from hospital outpatient clinics and surveillance programs run at four centres. The main outcome was the requirement for AAA repair or AAA related mortality (AAA events). The association between metformin prescription and AAA events was assessed using Kaplan-Meier analysis and Cox proportional hazard analysis., Results: Patients (1,080) with a mean (SD) initial AAA diameter of 46.1 (11.3) mm were followed for a mean (SD) of 2.5 (3.1) years until an AAA event (n = 454), death (n = 176), loss to follow up (n = 128), or completion of current follow up (n = 322). Patients with diabetes who were prescribed metformin (adjusted HR 0.63, 95% CI 0.44-0.93), but not patients with diabetes who were not prescribed metformin (adjusted HR 1.15, 95% CI 0.83-1.59), had a lower incidence of AAA events compared with those without diabetes. Findings were similar in sensitivity analyses restricted to patients with an initial AAA diameter ≤50 mm and patients with a minimum follow up of six months before an AAA event., Conclusions: These findings suggest that clinically important AAA events may be reduced in patients with diabetes who are prescribed metformin, but not those with diabetes receiving other treatments. A randomised controlled trial is needed to definitively test whether metformin reduces AAA related clinical events in patients with small AAAs who do not have diabetes., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Type 2 diabetes mellitus and other chronic cardio-metabolic conditions are significant contributors to the large disparities in life expectancy between Indigenous and non-Indigenous Australians. Type 2 diabetes is more prevalent from a young age among Indigenous Australians and is often preceded by a cluster of risk factors, including central obesity, dyslipidaemia, albuminuria and socio-economic disadvantage. Management of type 2 diabetes in Australian Indigenous peoples can be challenging in the setting of limited resources and socio-economic disadvantage. Key strategies to address these challenges include working in partnership with patients, communities and primary healthcare services ( PHC, Aboriginal community controlled and government services) and working in a multidisciplinary team. Population prevention measures are required within and beyond the health system, commencing as early as possible in the life course. [ABSTRACT FROM AUTHOR]

Objective: To summarise the reported lactic acidosis cases associated with metformin from the Australian Therapeutic Goods Administration (TGA) and estimate the incidence of metformin-associated lactic acidosis (MALA) in Australia., Method: All "lactic acidosis" cases associated with metformin and reported to the TGA between January 1971 and October 2014 were included. Data extracted included patient demographics, medical history and co-existing conditions, metformin dosage and relevant pathology results., Result: A total of 152 cases of suspected MALA were included in this study. For 20 patients the outcome was unknown. There were 23 patients (n=132, 17.4%) reported as deceased. Plasma lactate levels were higher in non-survivors (p=0.02). Thirty-five patients (n=132, 26.5%) were reported to have at least one pre-existing contraindication to the use of metformin; this proportion was not different between patients who died or survived. Renal impairment was the most common contraindication. Approximately 75% of patients were reported to have at least one clinical condition which might cause acidosis. Metformin dosage, plasma lactate and serum creatinine were not correlated. Based on the cases reported to the TGA, the incidence of MALA in Australia was estimated to be 2.3 (95% CI, 1.5-3.1) cases per 100,000 patient-years between 1997 and 2011., Conclusion: Pre-existing clinical conditions, such as renal impairment, and acute illnesses associated with lactic acidosis were frequently reported in the cases of MALA. The estimated incidence of MALA was lower than in most previous studies in other countries, probably due to the nature of spontaneous reports to the TGA., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: To compare the pharmacokinetics of metformin between diabetic Indigenous (Aboriginal and Torres Strait Islander) and non-Indigenous patients., Methods: An observational, cross-sectional study was conducted on type 2 diabetic Indigenous and non-Indigenous patients treated with metformin. Blood samples were collected to determine metformin, lactate, creatinine and vitamin B12 concentrations and glycosylated haemoglobin levels. A population model was used to determine the pharmacokinetic parameters., Results: The Indigenous patients (median age 55 years) were younger than the non-Indigenous patients (65 years), with a difference of 10 years (95% confidence interval 6-14 years, P < 0.001). The median glycosylated haemoglobin was higher in the Indigenous patients (8.5%) than in the non-Indigenous patients (7.2%), with a difference of 1.4% (0.8-2.2%, P < 0.001). Indigenous patients had a higher creatinine clearance (4.3 l h(-1) ) than the non-Indigenous patients (4.0 l h(-1) ), with a median difference of 0.3 l h(-1) (0.07-1.17 l h(-1) ; P < 0.05). The ratio of the apparent clearance of metformin to the creatinine clearance in Indigenous patients (13.1, 10.2-15.2; median, interquartile range) was comparable to that in non-Indigenous patients (12.6, 9.9-14.9). Median lactate concentrations were also similar [1.55 (1.20-1.88) vs. 1.60 (1.35-2.10) mmol l(-1) ] for Indigenous and non-Indigenous patients, respectively. The median vitamin B12 was 306 pmol l(-1) (range 105-920 pmol l(-1) ) for the Indigenous patients., Conclusions: There were no significant differences in the pharmacokinetics of metformin or plasma concentrations of lactate between Indigenous and non-Indigenous patients with type 2 diabetes mellitus. Further studies are required in Indigenous patients with creatinine clearance <30 ml min(-1) ., (© 2014 The British Pharmacological Society.)

The article presents a response to the review article by Wong published in this journal, which examined the role of spontaneous miscarriage in preventing the risk of spontaneous and recurrent miscarriage in pregnant women with polycystic ovary syndrome (PCOS). The authors cite randomized controlled trials and meta-analyses that studied the effect of metformin on miscarriage rate in PCOS patients. The administration of metformin is deemed safe under the Australian risk categorization.