Challenging Clinical Perspectives in Type 2 Diabetes with Tirzepatide, a First-in-Class Twincretin.

Tirzepatide is a first-in-class GIP/GLP-1 receptor agonist ('twincretin')-a single molecule that acts as an agonist at both glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. In the SURPASS clinical trial program in type 2 diabetes mellitus (T2D), tirzepatide was associated with unprecedented reductions in HbA1c, clinically significant weight loss and other metabolic benefits, combined with low rates of hypoglycaemia across a wide range of patient characteristics. The safety and adverse event rate for tirzepatide appears comparable to that of GLP-1 receptor agonists. Although results from dedicated cardiovascular (CV) and kidney trials are currently not available, information to date suggests that tirzepatide may have CV and kidney benefits in people with T2D. Tirzepatide has been approved for the treatment of T2D in the USA, United Arab Emirates, European Union, Japan and Australia. Here, we review how tirzepatide will fit into the T2D treatment continuum. We also consider future directions with tirzepatide in T2D, including its potential for targeting cardio-renal-metabolic disease in T2D, and discuss how tirzepatide-and other co-agonists in development-may challenge current approaches for management of T2D.

Early type 2 diabetes treatment intensification with glucagon-like peptide-1 receptor agonists in primary care: An Australian perspective on guidelines and the global evidence.

Early and intensive management of type 2 diabetes has been shown to delay disease progression, reduce the risk of cardiorenal complications and prolong time to treatment failure. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are being increasingly recognized for their potential in early disease management, with recent guideline updates recommending second-line use of this injectable drug class alongside oral glucose-lowering drugs. GLP-1RAs target at least six of the eight core defects implicated in the pathogenesis of type 2 diabetes and offer significant glycaemic and weight-related improvements over other second-line agents in head-to-head trials. In addition, placebo-controlled clinical trials have shown cardiovascular protection with GLP-1RA use. Even so, this therapeutic class is underused in primary care, largely owing to clinical inertia and patient-related barriers to early intensification with GLP-1RAs. Fortunately, clinicians can overcome barriers to treatment acceptance through patient education and training, and management of treatment expectations. In this review we comment on global and Australian guideline updates and evidence in support of early intensification with this therapeutic class, and provide clinicians with practical advice for GLP-1RA use in primary care.

The Australian Obesity Management Algorithm: A simple tool to guide the management of obesity in primary care.

Obesity is a complex and multifactorial chronic disease with genetic, environmental, physiological and behavioural determinants that requires long-term care. Obesity is associated with a broad range of complications including type 2 diabetes, cardiovascular disease, dyslipidaemia, metabolic associated fatty liver disease, reproductive hormonal abnormalities, sleep apnoea, depression, osteoarthritis and certain cancers. An algorithm has been developed (with PubMed and Medline searched for all relevant articles from 1 Jan 2000-1 Oct 2021) to (i) assist primary care physicians in treatment decisions for non-pregnant adults with obesity, and (ii) provide a practical clinical tool to guide the implementation of existing guidelines (summarised in Appendix 1) for the treatment of obesity in the Australian primary care setting. MAIN RECOMMENDATIONS AND CHANGES IN MANAGEMENT: Treatment pathways should be determined by a person's anthropometry (body mass index (BMI) and waist circumference (WC)) and the presence and severity of obesity-related complications. A target of 10-15% weight loss is recommended for people with BMI 30-40 kg/m2 or abdominal obesity (WC > 88 cm in females, WC > 102 cm in males) without complications. The treatment focus should be supervised lifestyle interventions that may include a reduced or low energy diet, very low energy diet (VLED) or pharmacotherapy. For people with BMI 30-40 kg/m2 or abdominal obesity and complications, or those with BMI > 40 kg/m2 a weight loss target of 10-15% body weight is recommended, and management should include intensive interventions such as VLED, pharmacotherapy or bariatric surgery, which may be required in combination. A weight loss target of > 15% is recommended for those with BMI > 40 kg/m2 and complications and they should be referred to specialist care. Their treatment should include a VLED with or without pharmacotherapy and bariatric surgery.

Transient receptor potential melastatin 3 dysfunction in post COVID-19 condition and myalgic encephalomyelitis/chronic fatigue syndrome patients.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multisystemic condition associated with post-infectious onset, impaired natural killer (NK) cell cytotoxicity and impaired ion channel function, namely Transient Receptor Potential Melastatin 3 (TRPM3). Long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has resulted in neurocognitive, immunological, gastrointestinal, and cardiovascular manifestations recently recognised as post coronavirus disease 2019 (COVID-19) condition. The symptomatology of ME/CFS overlaps significantly with post COVID-19; therefore, this research aimed to investigate TRPM3 ion channel function in post COVID-19 condition patients. METHODS: Whole-cell patch-clamp technique was used to measure TRPM3 ion channel activity in isolated NK cells of N = 5 ME/CFS patients, N = 5 post COVID-19 patients, and N = 5 healthy controls (HC). The TRPM3 agonist, pregnenolone sulfate (PregS) was used to activate TRPM3 function, while ononetin was used as a TRPM3 antagonist. RESULTS: As reported in previous research, PregS-induced TRPM3 currents were significantly reduced in ME/CFS patients compared with HC (p = 0.0048). PregS-induced TRPM3 amplitude was significantly reduced in post COVID-19 condition compared with HC (p = 0.0039). Importantly, no significant difference was reported in ME/CFS patients compared with post COVID-19 condition as PregS-induced TRPM3 currents of post COVID-19 condition patients were similar of ME/CFS patients currents (p > 0.9999). Isolated NK cells from post COVID-19 condition and ME/CFS patients were resistant to ononetin and differed significantly with HC (p < 0.0001). CONCLUSION: The results of this investigation suggest that post COVID-19 condition patients may have impaired TRPM3 ion channel function and provide further evidence regarding the similarities between post COVID-19 condition and ME/CFS. Impaired TRPM3 channel activity in post COVID-19 condition patients suggest impaired ion mobilisation which may consequently impede cell function resulting in chronic post-infectious symptoms. Further investigation into TRPM3 function may elucidate the pathomechanism, provide a diagnostic and therapeutic target for post COVID-19 condition patients and commonalities with ME/CFS patients.

Efficacy and Safety of Nutrient Supplements for Glycaemic Control and Insulin Resistance in Type 2 Diabetes: An Umbrella Review and Hierarchical Evidence Synthesis.

Background: Nutrient supplements are widely used for type 2 diabetes (T2D), yet evidence-based guidance for clinicians is lacking. Methods: We searched the four electronic databases from November 2015−December 2021. The most recent, most comprehensive, high-ranked systematic reviews, meta-analyses, and/or umbrella reviews of randomised controlled trials in adults with T2D were included. Data were extracted on study characteristics, aggregate outcome measures per group (glycaemic control, measures of insulin sensitivity and secretion), adverse events, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessments. Quality was assessed using A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2). Results: Twelve meta-analyses and one umbrella review were included. There was very low certainty evidence that chromium, Vitamin C, and omega-3 polyunsaturated fatty acids (Ω-3 PUFAs) were superior to placebo for the primary outcome of glycated hemoglobin (HbA1c) (Mean Difference/MD −0.54, −0.54 and ES −0.27, respectively). Probiotics were superior to placebo for HbA1c (Weighted Mean Difference/WMD −0.43%). There was very low certainty evidence that Vitamin D was superior to placebo for lowering HbA1c in trials of <6 months (MD −0.17%). Magnesium, zinc, Vitamin C, probiotics, and polyphenols were superior to placebo for FBG. Vitamin D was superior to placebo for insulin resistance. Data on safety was limited. Conclusions: Future research should identify who may benefit from nutrient supplementation, safety, and optimal regimens and formulations.

Integrative Medicine in General Practice in Australia: A Mixed-Methods Study Exploring Education Pathways and Training Needs.

BACKGROUND: Globally, a substantial proportion of general practitioners (GPs) incorporate integrative medicine (IM) into their clinical practice. OBJECTIVE: This study aimed to map the IM education and training pathways and needs of a cohort of Australian GPs who are members of the Royal Australian College of General Practitioners' IM Specific Interest Network, which is a group of GPs with interest in IM. METHODS: We conducted a mixed-methods study comprising of an online, cross-sectional survey supplemented with in-depth semi-structured interviews. Data from the survey and interviews were initially analysed separately and then combined. RESULTS: Eighty-three (83) of 505 eligible GPs/GPs in training (16.4%) participated in the survey, and 15 GPs were interviewed. Results from the two datasets either converged or were complementary. Almost half (47%) of survey respondents had undertaken formal undergraduate or postgraduate IM education, a short course (63%), informal education (71%) or self-education (54%), in at least one of 20 IM modalities listed. Interviewees affirmed there was no single education pathway in IM. Survey respondents who identified as practicing IM were significantly more likely to have IM education, positive attitudes towards IM, particularly natural products, and higher self-rated IM knowledge and competencies. However, knowledge gaps were identified in professional skills domains of population health and context, and organisational and legal dimensions of applied IM practice. Interviewees also highlighted a range of professional and systemic barriers to the practice of IM, education, and training. There was broad support for recognition of IM as a sub-specialty through formalised post-graduate training and accreditation. Most survey respondents (62%) expressed interest in post-fellowship recognition of GPs with advanced skills in IM. CONCLUSION: Our findings demonstrate that it is important to define best practice in IM for GPs in Australia and provide a standardised pathway towards recognition of advanced skills in IM.

Sodium-glucose cotransporter 2 inhibitor effects on heart failure hospitalization and cardiac function: systematic review.

AIMS: To systematically review randomized controlled trials assessing effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) on hospitalization for heart failure (HHF) and cardiac structure/function and explore randomized controlled trial (RCT)-derived evidence for SGLT2i efficacy mechanisms in heart failure (HF). METHODS AND RESULTS: Systematic searches of Medline and Embase were performed. In seven trials [3730-17 160 patients; low risk of bias (RoB)], SGLT2is significantly reduced the relative risk of HHF by 27-39% vs. placebo, including in two studies in patients with HF with reduced ejection fraction with or without type-2 diabetes mellitus (T2DM). Improvements in conventional cardiovascular risk factors, including glycaemic levels, cannot account for these effects. Five trials (56-105 patients; low RoB) assessed the effects of 6-12 months of SGLT2i treatment on left ventricular structure/function; four reported significant improvements vs. placebo, and one did not. Five trials (low RoB) assessed SGLT2i treatment effects on serum N-terminal pro B-type natriuretic peptide levels; significant reductions vs. placebo were reported after 8-12 months (two studies; 3730-4744 patients) but not ≤12 weeks (three studies; 80-263 patients). Limited available RCT-derived evidence suggests various possible cardioprotective SGLT2i mechanisms, including improved haemodynamics (natriuresis and reduced interstitial fluid without blood volume contraction/neurohormonal activation) and vascular function, enhanced erythropoiesis, reduced tissue sodium and epicardial fat/inflammation, decreased sympathetic tone, and beneficial changes in cellular energetics. CONCLUSIONS: Sodium-glucose cotransporter 2 inhibitors reduce HHF regardless of T2DM status, and reversal of adverse left ventricular remodelling likely contributes to this efficacy. Hypothesis-driven mechanistic trials remain sparse, although numerous trials are planned or ongoing.

Management of patients with type 2 diabetes and cardiovascular disease in primary care.

BACKGROUND AND OBJECTIVES: Approximately 65% of cardiovascular disease (CVD)-related deaths in Australia occur in people with diabetes or pre-diabetes. The aim of this study was to investigate general practice management of risk factors among patients with both conditions. METHOD: This was a cross-sectional study of 33,559 adult patients with both type 2 diabetes and CVD at 1 November 2018, using the general practice data program MedicineInsight. RESULTS: One-third of patients did not have a record in their current medications list for all three recommended medicines to reduce cardiovascular risk. Potentially suboptimal monitoring and achievement of targets for diabetes and cardiovascular risk factors was also identified. Most patients using metformin-based combination therapy were prescribed blood glucose-lowering medicines that do not have evidence of cardiovascular benefit. DISCUSSION: These data suggest opportunities to support general practices to optimise patient management. Datasets such as MedicineInsight can help practices identify patients who may benefit from recall.

Global survey investigating causes of treatment inertia in type 2 diabetes cardiorenal risk management.

AIM: To explore reasons behind treatment inertia in current approaches to early cardiorenal risk management in type 2 diabetes (T2D). METHODS: A global, web-based, quantitative panel survey of primary care physicians (PCPs) and primary care diabetes specialists treating people living with T2D. The questions covered current management of T2D, particularly the use of sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors as second-/third-line therapies. RESULTS: Of 1677 respondents from 18 countries who completed the survey, 73.4% were responsible for second-/third-line therapy initiation. Two thirds had modified treatment decisions based on recent cardiovascular outcomes trials (CVOTs). Respondents cited restricted access to therapies and limits on regular appointments as the greatest barriers to second-/third-line therapy prescription. Although 81.6% agreed that early intensification to second-/third-line therapies is associated with clinical benefits, 46.1% of respondents still reserve these for later lines of therapy, and 23.8% would not consider changing therapeutic approach in patients with well-controlled T2D but increasing cardiovascular risk. CONCLUSIONS: Substantial barriers still prevent optimization of primary setting T2D patient care. Education programs which enable PCPs to translate CVOT evidence into clinical benefits for patients with T2D could address many of the remaining knowledge gaps identified.

Shared Medical Appointments and Mindfulness for Type 2 Diabetes-A Mixed-Methods Feasibility Study.

Introduction: Type 2 diabetes (T2DM) is a major health concern with significant personal and healthcare system costs. There is growing interest in using shared medical appointments (SMAs) for management of T2DM. We hypothesize that adding mindfulness to SMAs may be beneficial. This study aimed to assess the feasibility and acceptability of SMAs with mindfulness for T2DM within primary care in Australia. Materials and Methods: We conducted a single-blind randomized controlled feasibility study of SMAs within primary care for people with T2DM living in Western Sydney, Australia. People with T2DM, age 21 years and over, with HbA1c > 6.5% or fasting glucose >7.00 mmol/L within the past 3 months were eligible to enroll. The intervention group attended six 2-h programmed SMAs (pSMAs) which were held fortnightly. pSMAs included a structured education program and mindfulness component. The control group received usual care from their healthcare providers. We collected quantitative and qualitative data on acceptability as well as glycemic control (glycated hemoglobin and continuous glucose monitoring), lipids, anthropometric measures, blood pressure, self-reported psychological outcomes, quality of life, diet, and physical activity using an ActiGraph accelerometer. Results: Over a 2-month period, we enrolled 18 participants (10 females, 8 males) with a mean age of 58 years (standard deviation 9.8). We had 94.4% retention. All participants in the intervention group completed at least four pSMAs. Participants reported that attending pSMAs had been a positive experience that allowed them to accept their diagnosis and empowered them to make changes, which led to beneficial effects including weight loss and better glycemic control. Four pSMA participants found the mindfulness component helpful while two did not. All of the seven participants who contributed to qualitative evaluation reported improved psychosocial wellbeing and found the group setting beneficial. There was a significant difference in total cholesterol levels at 12 weeks between groups (3.86 mmol/L in intervention group vs. 4.15 mmol/L in the control group; p = 0.025) as well as pain intensity levels as measured by the PROMIS-29 (2.11 vs. 2.38; p = 0.034). Conclusion: pSMAs are feasible and acceptable to people with T2DM and may result in clinical improvement. A follow-up fully-powered randomized controlled trial is warranted. Clinical Trial Registration: Australia and New Zealand Clinical Trial Registry, identifier ACTRN12619000892112.

Integrating Traditional and Complementary Medicine Recommendations into Clinical Practice Guidelines for People with Diabetes in Need of Palliative and End-of-Life Care: A Scoping Review.

Objectives: This study was conducted before an evidence review on Traditional and Complementary Medicine (TCM) to update the clinical practice guidelines (CPGs): "Deciding palliative and end-of-life (P/EoL) care for people with diabetes." The aim was to frame the PICO (population/problems, interventions/comparisons, and outcomes), ascertain their importance, and identify other modifying factors for grading recommendations. Design: A systematic scoping review mapped information about diabetes P/EoL problems and outcomes, TCM use, provision, benefits and risks, and stakeholder preferences and values. Thirteen electronic databases were searched in 2017/18 until no new information was identified. Relevant data were extracted, rated for quality, directness, and relevance, and synthesized using triangulation methods. Excluded was diabetes prevention or treatment, as this is not an important P/EoL problem. Results: Of the 228 included articles, except for diabetes P/EoL problems, insufficient direct evidence led to data being extrapolated from either adults with diabetes or any P/EoL diagnosis. The findings affirmed that caring for people with diabetes in need of P/EoL care is complex due to multiple fluctuating needs that are influenced by the P/EoL trajectories (stable, unstable, deteriorating, terminal, or bereaved), multimorbidity, and difficult-to-manage chronic and acute problems. The only problem specific to diabetes P/EoL care, was unstable glycemia. Over 50 TCM interventions commonly used by patients and/or provided by services were identified, of which, many might simultaneously address multiple problems and 18 had been appraised in systematic reviews. Physical and psychologic symptom reliefs were most often evaluated; however, these were only one aspect of a "good death." Other important outcomes were the quality and location of care, personal agency, relationships, preparations for the dying process, spirituality, and affirmation of the whole person. Other important modifying factors included opportunity costs, affordability, availability, preferences, cultural appropriateness, and alignment with beliefs about the meaning of illness and death. Conclusions: There is a role for TCM in the multidisciplinary holistic P/EoL care of people with diabetes. Due to the paucity of evidence specific to this population, the generalizability of some of these results is broader and the updated CPG will also need to consider indirect evidence from other patient groups. Along with recommendations about indications for TCM use, the CGP should provide guidance on ceasing unnecessary interventions, reducing polypharmacy and managing unstable glycemia is required. Before ceasing a TCM, a broader risk-benefit analysis is recommended, as unlike many conventional therapies, there may be multiple benefits warranting its continuation.

Improving Type 2 Diabetes Management in General Practice Using a Second-Generation Basal Insulin Analogue Insulin Glargine 300 U/mL: A Practical Guide.

Type 2 diabetes management can be improved by the use of second-generation basal insulin analogues as the first choice on commencement of insulin, in this instance focussing on insulin glargine 300 U/mL (Gla-300). The clinical application of the use of Gla-300 include advantages such as less intra- and interpatient variability in glucose control resulting in rather less hypoglycaemia, longer duration of action and greater flexibility in the timing of administration thus suiting a wide range of patient presentations.Funding: Sanofi Australia.

Managing Cardiovascular Risk in Type 2 Diabetes: What Do the Cardiovascular Outcome Trials Mean for Australian Practice?

Understanding the implications of cardiovascular (CV) outcomes data of glucose-lowering agents on the management of type 2 diabetes mellitus can be challenging for many primary practitioners. Amongst different classes of diabetes medications assessed for CV safety, several agents within the sodium-glucose transport protein-2 inhibitor and glucagon-like peptide-1 receptor agonists classes have demonstrated CV risk reduction. Applying the trial findings to patients typically seen in clinical practice, such as those with established CV disease and those with multiple CV risk factors without established CV disease, requires further clarity. To bridge this gap in our current knowledge, the aim of this review was to utilise expert-driven opinions on common case scenarios and practical recommendations on the most appropriate choice of agents, according to an individual patient's clinical risk profile (CV and kidney disease), treatment preference and reimbursement environment from an Australian perspective.Funding: Boehringer Ingelheim Australia.

Managing Obesity in Primary Care: Breaking Down the Barriers.

Several Australian obesity management guidelines have been developed for general practice but, to date, implementation of these guidelines has been shown to be inadequate. In this review, we explore the barriers to obesity treatment and propose a four-stage plan to manage individuals with obesity in general practice using a framework of a multidisciplinary team. FUNDING: Novo Nordisk.

SGLT2 inhibitors with cardiovascular benefits: Transforming clinical care in Type 2 diabetes mellitus.

Cardiovascular risk reduction in individuals with Type 2 diabetes mellitus (T2DM) is a key part of clinical management. Sodium-glucose co-transporter (SGLT2) inhibitors improve glycaemic control, reduce body weight and decrease blood pressure. In addition, the SGLT2 inhibitors empagliflozin and canagliflozin reduced the risk of composite cardiovascular events in high-risk individuals with T2DM in the EMPA-REG OUTCOME trial and the CANVAS Program, respectively. Empagliflozin also reduced cardiovascular deaths and improved renal outcomes. This class of agents should be considered in people with established cardiovascular disease, usually in combination with other glucose lowering medications, when satisfactory glycaemic control has not been achieved. The dose of insulin or sulfonylureas may need to be lowered when used with SGLT2 inhibitors, to reduce the risk of hypoglycaemia. Genitourinary infections can occur with SGLT2 inhibitors in a small proportion of people. In people with osteoporosis or prior amputation, it may be prudent to use empagliflozin rather than canagliflozin, based on the increased risk for bone fractures and amputations observed with canagliflozin in the CANVAS Program. SGLT2 inhibitors have the potential to transform the clinical care of persons with T2DM by not only improving glycaemic control but also reducing blood pressure, body weight and diabetes-related end-organ complications.

Use of 50/50 Premixed Insulin Analogs in Type 2 Diabetes: Systematic Review and Clinical Recommendations.

INTRODUCTION: Premixed insulin analogs represent an alternative to basal or basal-bolus insulin regimens for the treatment of type 2 diabetes (T2D). "Low-mix" formulations with a low rapid-acting to long-acting analog ratio (e.g., 25/75) are commonly used, but 50/50 formulations (Mix50) may be more appropriate for some patients. We conducted a systematic literature review to assess the efficacy and safety of Mix50, compared with low-mix, basal, or basal-bolus therapy, for insulin initiation and intensification. METHODS: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, LillyTrials.com, and NovoNordisk-trials.com were searched (11 or 13 Dec 2016) using terms for T2D, premixed insulin analogs, and/or Mix50. Studies (randomized, nonrandomized, or observational; English only) comparing Mix50 with other insulins (except human) and reporting key efficacy [glycated hemoglobin (HbA1c), fasting and postprandial glucose] and/or safety (hypoglycemia, weight gain) outcomes were eligible for inclusion. Narrative reviews, letters, editorials, and conference abstracts were excluded. Risk of bias in randomized trials was assessed using the Cochrane tool. RESULTS: MEDLINE and EMBASE searches identified 716 unique studies, of which 32 met inclusion criteria. An additional three studies were identified in the other databases. All 19 randomized trials except one were open label; risk of other biases was generally low. Although not conclusive, the evidence suggests that Mix50 may provide better glycemic control (HbA1c reduction) and, particularly, postprandial glucose reduction in certain patients, such as those with high carbohydrate diets and Asian patients, than low-mix and basal therapy. Based on this evidence and our experience, we provide clinical guidance on factors to consider when deciding whether Mix50 is appropriate for individual patients. CONCLUSIONS: Mix50 may be more suitable than low-mix therapy for certain patients. Clinicians should consider not only efficacy and safety but also patient characteristics and preferences when tailoring insulin treatment to individuals with T2D. FUNDING: Eli Lilly.

Peer-to-Peer, Interactive GP Education can Reduce Barriers to Best Practice in Diabetes Management.

INTRODUCTION: Perceived difficulties in initiating insulin in patients with type 2 diabetes (T2D) may prevent many general practitioners (GPs) from using insulin even when recommended in guidelines. This paper describes a Royal Australian College of General Practitioners accredited education program on starting insulin in T2D, and its impact on GPs' attitudes and behavior. METHODS: A faculty comprising GPs with diabetes expertise, Credentialed Diabetes Nurse Educators, and endocrinologist developed and implemented the education program. The program content was highly procedure focussed, emphasizing simple, best-practice processes for starting insulin therapy and focussing on multidisciplinary models of care. The highly interactive format of the workshops included peer-to-peer learning, in which education was led by diabetes-experienced GP educators, as well as case study-based approaches and small group discussions. GP attendees were asked to rate their individual confidence and attitudes at the beginning and end of the meeting. In addition, participants (n = 220) from two workshops in 2013 were sent a survey 3 months after the meeting to gauge the longer-term impact on their clinical practice. RESULTS: Since 2008, more than 2500 GPs have attended the workshops, and report substantial improvements in confidence; after attending, more GPs were willing to start insulin within their practice. Evaluations at 3 months post-meeting indicate that the increased confidence was associated with behavioral changes in the subgroup evaluated at this time (n = 48). Success of this program was attributed to peer-to-peer education, multidisciplinary input, easily implemented best practice procedures and checklists for starting insulin, and constant adjustment of meeting process and content based on feedback and guideline changes. CONCLUSION: A peer-to-peer, interactive GP education program reduced GPs' perceptions of the difficulties of starting insulin in T2D and achieved changes in attendees' clinical practice. This education program offers an effective approach to overcome the therapeutic inertia that is too common in diabetes management.

Diet and diabetes.

BACKGROUND: Guidelines for the prevention and management of type 2 diabetes mellitus (T2DM) reinforce lifestyle management, yet advice to guide general practitioners on principles around dietary choices is needed. OBJECTIVE: This article provides current evidence regarding the differing diets in diabetes prevention and management once T2DM arises, including the role in management of complications such as hypoglycaemia. DISCUSSION: Diets should incorporate weight maintenance or loss, while complementing changes in physical activity to optimise the metabolic effects of dietary advice. Using a structured, team-care approach supports pragmatic and sustainable individualised plans, while incorporating current evidence-based dietary approaches.

Early and tight glycaemic control - the key to managing type 2 diabetes.

BACKGROUND: The prevalence of type 2 diabetes is on the rise in Australia. A large number of patients with type 2 diabetes do not reach currently recommended glycaemic targets. OBJECTIVE: This article looks at how clinical inertia contributes to suboptimal glycaemic control in patients with type 2 diabetes, describes the 'legacy' effect of early high HbA1c levels and highlights the importance of early, tight glycaemic control. DISCUSSION: Early, tight glycaemic control in patients with type 2 diabetes has been shown to result in better outcomes in terms of micro- and macrovascular disease and mortality even if control is relaxed later in the course of the disease. Clinical inertia is one of the contributing factors that prevent patients from reaching glycaemic targets. A proactive approach to treating type 2 diabetes is recommended: therapy should be individualised with early consideration of combination therapy and ongoing reinforcement of lifestyle modification messages. In newly diagnosed patients, the goal should be to achieve an HbA1c of.

St. John's wort and Kava in treating major depressive disorder with comorbid anxiety: a randomised double-blind placebo-controlled pilot trial.

OBJECTIVE: We report the first randomised controlled trial (RCT) using a combination of St. John's wort (SJW) and Kava for the treatment of major depressive disorder (MDD) with comorbid anxiety. METHODS: Twenty-eight adults with MDD and co-occurring anxiety were recruited for a double-blind RCT. After a placebo run-in of 2 weeks, the trial had a crossover design testing SJW and Kava against placebo over two controlled phases, each of 4 weeks. The primary analyses used intention-to-treat and completer analyses. RESULTS: On both intention-to-treat (p = 0.047) and completer analyses (p = 0.003), SJW and Kava gave a significantly greater reduction in self-reported depression on the Beck Depression Inventory (BDI-II) over placebo in the first controlled phase. However, in the crossover phase, a replication of those effects in the delayed medication group did not occur. Nor were there significant effects on anxiety or quality of life. CONCLUSION: There was some evidence of antidepressant effects using SJW and Kava in a small sample with comorbid anxiety. Possible explanations for the absence of anxiolysis may include a potential interaction with SJW, the presence of depression, or an inadequate dose of Kava.