Type 2 Diabetes Current Awareness Bulletin April 2020

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Title: Coronavirus infections and type 2 diabetes-shared pathways with therapeutic implications. Citation: Endocrine reviews; Apr 2020 Author(s): Drucker, Daniel J Abstract: Individuals with diabetes are at increased risk for bacterial, mycotic, parasitic and viral infections. The severe acute respiratory syndrome (SARS)-CoV2 (also referred to as COVID-19) coronavirus pandemic highlights the importance of understanding shared disease pathophysiology potentially informing therapeutic choices in individuals with Type 2 diabetes (T2D). Two coronavirus receptor proteins, Angiotensin Converting Enzyme 2 (ACE2) and Dipeptidyl Peptidase-4 (DPP4) are also established transducers of metabolic signals and pathways regulating inflammation, renal and cardiovascular physiology, and glucose homeostasis. Moreover, glucose-lowering agents such as the DPP4 inhibitors, widely used in subjects with T2D, are known to modify the biological activities of multiple immunomodulatory substrates. Here we review the basic and clinical science spanning the intersections of diabetes, coronavirus infections, ACE2, and DPP4 biology, highlighting clinical relevance and evolving areas of uncertainty underlying the pathophysiology and treatment of T2D in the context of coronavirus infection.

Title: Making sense of blood glucose data and self-management in individuals with type 2 diabetes mellitus: A qualitative study. Citation: Journal of clinical nursing; Apr 2020 Author(s): Despins, Laurel A; Wakefield, Bonnie J Aims and Objectives: To describe individuals with type 2 diabetes mellitus sensemaking of blood glucose data and other influences impacting self-management behavior. Background: Type 2 diabetes mellitus prevalence is increasing globally. Adherence to effective diabetes self-management regimens is an ongoing health care challenge. Examining individuals' sensemaking processes can advance staff knowledge of and improve diabetes self-management behavior. Design: A qualitative exploratory design examining how individuals make sense of blood glucose data and symptoms, and the influence on self-management decisions. Methods: Sixteen one-on-one interviews with adults diagnosed with type 2 diabetes mellitus using a semi-structured interview guide were conducted March to May 2018. An inductive-deductive thematic analysis of data using the Sensemaking Framework for Chronic Disease Self-Management was utilized. The consolidated criteria for reporting qualitative research (COREQ) checklist was used in completing this paper. Results: Three main themes described participants' type 2 diabetes mellitus sensemaking and influences on self-management decisions: classifying blood glucose data, building mental models, and making self-management decisions. Participants classified glucose levels based on prior personal experiences. Participants learned about diabetes from classes, personal experience, health information technology, and their social network. Seven participants expressed a need for periodic refreshing of diabetes knowledge. Conclusion: Individuals use self-monitored glucose values and/or HbA1C values to evaluate glucose control. When using glucose values, they analyze the context in which the value was obtained through the lens of personal parameters and expectations. Understanding how individuals make sense of glycemic data and influences on diabetes self-management behavior with periodic reassessment of this understanding can guide the healthcare team in optimizing collaborative individualized care plans. Relevance To Clinical Practice: Nurses must assess sensemaking processes in self-management decisions. Periodic "refresher" diabetes education may be needed for individuals with type 2 diabetes mellitus.

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Title: Low-Carbohydrate Diets in the Management of Obesity and Type 2 Diabetes: A Review from Clinicians Using the Approach in Practice. Citation: International journal of environmental research and public health; Apr 2020; vol. 17 (no. 7) Author(s): Kelly, Tara; Unwin, David; Finucane, Francis Abstract: Low-carbohydrate diets are increasingly used to help patients with obesity and type 2 diabetes. We sought to provide an overview of the evidence for this treatment approach, considering the epidemiology and pathophysiology of obesity and diabetes in terms of carbohydrate excess. We describe the mechanistic basis for the clinical benefits associated with nutritional ketosis and identify areas of practice where the evidence base could be improved. We summarize the key principles which inform our approach to treating patients with low-carbohydrate diets. The scientific controversy relating to these diets is real but is consistent with the known challenges of any dietary interventions and also the limitations of nutritional epidemiology. Secondly, notwithstanding any controversy, international guidelines now recognize the validity and endorse the use of these diets as a therapeutic nutritional approach, in appropriate patients. Thirdly, we have found that early de-prescription of diabetes medications is essential, in particular insulin, sulphonylureas, and sodium-glucose cotransporter (SGLT2) inhibitors. Fourthly, we encourage patients to eat ad libitum to satiety, rather than calorie counting per se. Furthermore, we monitor cardiovascular risk factors frequently, as with all patients with obesity or diabetes, but we do not necessarily consider an increase in low-density lipoprotein (LDL)-cholesterol as an absolute indication to stop these diets, as this is usually related to large LDL particles, which are not associated with increased cardiovascular risk. In the absence of large randomized controlled trials with cardiovascular and other hard endpoints, adopting a low-carbohydrate diet is a legitimate and potentially effective treatment option for patients with diabetes or obesity.

Title: Effect of Hemoglobin A1c Reduction or Weight Reduction on Blood Pressure in Glucagon-Like Peptide-1 Receptor Agonist and Sodium-Glucose Cotransporter-2 Inhibitor Treatment in Type 2 Diabetes Mellitus: A Meta-Analysis. Citation: Journal of the American Heart Association; Apr 2020; vol. 9 (no. 7); p. e015323 Author(s): Hu, Mengdie; Cai, Xiaoling; Yang, Wenjia; Zhang, Simin; Nie, Lin; Ji, Linong Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have shown their beneficial effects on cardiovascular outcomes and multiple cardiovascular risk factors, including hypertension. However, the mechanism of blood pressure (BP)-lowering effects of these agents has not been elucidated. This study aims to evaluate the effect of hemoglobin A1c reduction or body weight reduction with GLP-1RA treatment and SGLT2i treatment on BP changes in patients with type 2 diabetes mellitus. Methods and Results: Studies were identified by a search of MEDLINE, EMBASE, and the Cochrane Central Register until June 2019. Meta-regression analysis was performed to evaluate the association between hemoglobin A1c reduction or body weight reduction and changes of BP. A total of 184 trials were included. Both GLP-1RA and SGLT2i led to significant reductions in systolic BP (weighted mean difference, -2.856 and -4.331 mm Hg, respectively; P<0.001 for both) and diastolic BP (weighted mean difference, -0.898 and -2.279 mm Hg, respectively; P<0.001 for both). For both drug classes, hemoglobin A1c reduction was not independently associated with systolic BP reduction or diastolic BP reduction. In GLP-1RA treatment, weight reduction was positively associated with systolic BP reduction and diastolic BP reduction (β=0.821 and β=0.287, respectively; P<0.001 for both). In SGLT2i treatment, weight loss was significantly associated with systolic BP reduction (β=0.820; P=0.001) but was not associated with diastolic BP reduction. Conclusions: Treatment with GLP-1RA and SGLT2i led to significant reductions in BP in patients with type 2 diabetes mellitus. Weight reduction was significantly and independently associated with BP reductions in GLP-1RA treatment and SGLT2i treatment.

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Title: Clinical Review: Safety and Efficacy comparison between Sulfonylureas and Dipeptidyl Peptidase-4 Inhibitors as Second-Line Therapies in Type 2 Diabetes Mellitus. Citation: Current pharmaceutical design; Apr 2020 Author(s): Gillani, Syed Wasif; Moosvi, Arzu F Background: According to the World Health Organization (WHO), diabetes mellitus is considered the 7th leading cause of death from as of 2016, whilealmost half of all deaths related to high blood glucose occur before the age of 70. According to the 2019 American Diabetes Association's (ADA) guidelines, metformin is the first-line treatment for patients with Type 2 diabetes. Additional therapy is dependent on multiple patientspecific factors including cardiovascular risks, risk of hypoglycemia, metabolic changes, and cost. The objective of this systematic review is to analyze variables of interest in Type 2 diabetes including fasting blood glucose (FBG), post-prandial blood glucose (PPBG), hemoglobin A1c (HbA1c), microvascular complications, and cardiovascular outcomes in order to determine the shift towards the newer class of medications for type 2 diabetes. Methods: A systematic review was conducted using ScienceDirect as the primary source of obtaining articles. This review used PRISMA for reporting and GRACE for quality assessment of ten articles. Inclusion criteria for the review consisted of patients who were on metformin therapy for a sufficient amount of time, as defined by the trial's protocol, who were then initiated on either a sulfonylurea (glipizide or glimepiride) or a DPP-4 inhibitor (saxagliptin or linagliptin). The articles included in this review range from 2005-2019 that are written in English only. Exclusion criteria for this systematic review were articles in which patients were not initially started on metformin therapy, were diagnosed with Type 1 diabetes mellitus, and articles that were written in languages other than English. Results: After filtering 50 studies, 10 were selected for meeting the criteria of variables of interest. . Findings suggested a significant reduction in fasting plasma glucose with 154 mg/dL + 4 mg/dL as baseline, decreasing to 132 mg/dL + 4 mg/dL with the use of glipizide & metformin combination. A similar pattern was presented with use of saxagliptin & metformin in combination, but changes were less significant than glipizide. However, hypoglycemic events in patients who were taking glipizide with metformin versus saxagliptin with metformin; 13.4% of patients achieved HbA1c <7% without hypoglycemic events compared to the 22.2% of patients who achieved an HbA1c of <7% without hypoglycemic events. Conclusion: Despite the higher efficacious characteristics of sulfonylureas in lowering HbA1c, due to its reported hypoglycemic effects, DPP-4 inhibitors may be considered as a clinically stable choice for second-line therapy after completing maximally tolerated doses of metformin.. Sulfonylureas is considered better than DPP4 inhibitors for treatment in patients with cardiovascular disease history and low of hypoglycemia.

Title: Insulin U-500, the practical solution for treatment of patients with high insulin requirements. Citation: Current diabetes reviews; Apr 2020 Author(s): Mikhail, Nasser Background: Human regular insulin 500 (U-500) is 5 five times more concentrated than traditional regular human insulin (U-100). Thus, each 1 ml of U-500 contains 500 units of insulin as opposed to 100 units/ml with most types of insulin. Methods: Review of all pertinent clinical studies related to insulin U-500 up to February 12, 2020. Results: Insulin U-500 is indicated in patients with type 2 diabetes who require more than 200 units of insulin per day. Insulin U-500 has both prandial and basal actions, and can be injected as monotherapy in a convenient twice-daily regimen. Available data suggest that insulin U-500 is effective, associated with better compliance, and decreased injection pain compared with non-concentrated insulins. Its main limitations are hypoglycemia and weight gain, and possibility of dosing errors.

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Conclusions: Overall, insulin U-500 is an effective and safe treatment for patients with type 2 diabetes and insulin resistance. Randomized trials are needed to compare longterm efficacy and safety of insulin U-500 with other forms of insulin regimens.

Title: The effect of 'paying for performance' on the management of type 2 diabetes mellitus: a cross-sectional observational study. Citation: BJGP open; Apr 2020 Author(s): O'Connor, Raymond; O'Driscoll, Rory; O'Doherty, Jane; Hannigan, Ailish; O'Neill, Aoife; Teljeur, Conor; O'Regan, Andrew Background: The 'cycle of care' (COC) pay for performance (PFP) programme, introduced in 2015, has resourced Irish GPs to provide structured care to PCRS eligible patients with type 2 diabetes mellitus (T2DM).AIMTo investigate the effect of COC on management processes. Design & Setting: Cross-sectional observational study undertaken with two points of comparison (2014 and 2017) in participating practices (Republic of Ireland general practices), with comparator data from the United Kingdom National Diabetes Audit (UKNDA) 2015-2016.METHODInvitations to participate were sent to practices using a discussion forum for Health One clinical software. Participating practices provided data on the processes of care in the management of patients with T2DM. Data on PCRS eligible patients was extracted from the electronic medical record system of participating practices using secure customised software. Descriptive analysis, using IBM SPSS Statistics for Windows (version 25), was performed. Results: Of 250 practices invited, 41 practices participated (16.4%), yielding data from 3146 patients. There were substantial improvements in the rates of recording of glycosylated haemoglobin ([HbA1c] 53.1%-98.3%), total cholesterol ([TC] 59.2%-98.8%), urinary albumin:creatinine ratio ([ACR] 9.9%-42.3%), blood pressure ([BP] 61.4%-98.2%), and body-mass index ([BMI] 39.8%-97.4%) from 2014 to 2017. For the first time, rates of retinopathy screening (76.3%), foot review (64.9%), and influenza immunisation (69.9%) were recorded. Comparison of 2017 data with UKNDA 2015-2016 was broadly similar. Conclusion: The COC demonstrated much improved rates of recording of clinical and biochemical parameters, and improved achievement of targets in TC and BP, but not HbA1c. Results demonstrate substantial improvements in the processes and quality of care in the management of patients with T2DM.

Title: James Lind Alliance research priorities: should diet and exercise be used as an alternative to drugs for the management of type 2 diabetes or alongside them? Citation: Diabetic medicine: a journal of the British Diabetic Association; Apr 2020; vol. 37 (no. 4); p. 564-572 Author(s): England, C Y; Andrews, R C Aim: To review evidence on whether diet and exercise should be used as an alternative to drug therapy for the management of type 2 diabetes or alongside. Method: We present a narrative review that draws on evidence from other systematic reviews and meta-analyses, narrative reviews, trials and cohort studies. We focused mainly on glycaemic control rather than control of blood pressure or cholesterol. Results: Good-quality dietary advice that results in weight loss of >5% and physical activity interventions of >150 min/week of moderate to vigorous physical activity, combined with resistance exercise, can produce improvements in HbA1c similar to those produced by the addition of glucose-lowering drugs. These improvements can be seen at all stages of the disease. There are recognized interactions between glucose-lowering drugs and physical activity which may not be synergistic, but

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these are not well understood, and it is not clear if they are considered in clinical practice. Studies that explicitly compare drugs with diet or physical activity or control for drug use found that lifestyle could delay or reduce medication use, but most people eventually needed to progress to drug treatment. There are few studies, however, that provide strategies for the long-term maintenance of weight loss or physical activity. Conclusion: Diet and physical activity are of key importance in type 2 diabetes management, and attention to them improves glycaemic control and cardiovascular disease risk, but it is not yet known whether maintained lifestyle changes provide an alternative to drug therapy in the long term.

Title: The effects of dapagliflozin on cardio-renal risk factors in patients with type 2 diabetes with or without renin-angiotensin system inhibitor treatment: a post hoc analysis. Citation: Diabetes, obesity & metabolism; Apr 2020; vol. 22 (no. 4); p. 549-556 Author(s): Scholtes, Rosalie A; van Raalte, Daniël H; Correa-Rotter, Ricardo; Toto, Robert D; Heerspink, Hiddo J L; Cain, Valerie; Sjöström, C David; Sartipy, Peter; Stefánsson, Bergur V Aims: Renin-angiotensin system inhibitors (RASi) are the most effective treatments for diabetic kidney disease but significant residual renal risk remains, possibly because of other mechanisms of kidney disease progression unrelated to RAS that may be present. Sodium-glucose co-transporter-2 inhibitors reduce albuminuria and may complement RASi by offering additional renal protection. This post hoc analysis investigated the effects of dapagliflozin on cardio-renal risk factors in patients with type 2 diabetes (T2D) with increased albuminuria treated with or without RASi at baseline. Materials and Methods: We evaluated the effects of dapagliflozin 10 mg/day over 12-24 weeks across 13 placebo-controlled studies in patients with T2D with a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g at baseline. Patients were divided into two subgroups based on treatment with or without RASi at baseline. Results: Compared with patients with RASi at baseline (n = 957), patients without RASi (n = 302) were younger, had a shorter duration of diabetes (7 vs. 12 years), higher estimated glomerular filtration rate (eGFR) and lower UACR, serum uric acid (sUA), body weight and systolic blood pressure. Placebo-adjusted treatment effects of dapagliflozin on UACR, eGFR, glycated haemoglobin and haematocrit over 24 weeks were similar across groups. Mean reductions in body weight and sUA were more distinct in patients without RASi treatment at baseline. Conclusions: Treatment with dapagliflozin over 24 weeks provides similar clinically relevant improvements in metabolic and haemodynamic parameters, and similar reductions in UACR, in patients with T2D with elevated albuminuria treated with or without RASi at baseline.

Title: Importance of intensive blood pressure control in type 2 diabetes: Mechanisms, treatments and current guidelines. Citation: Diabetes, obesity & metabolism; Apr 2020; vol. 22 Author(s): Marre, Michel Abstract: Observational and interventional studies have shown that intensified blood pressure (BP) reduction can benefit people with diabetes. Because of their special haemodynamic properties, renin-angiotensin-aldosterone system (RAAS) blockers are recommended. The results of the BP arm of the ADVANCE study strongly support the recently updated European Society of Cardiology/European Association of Diabetes recommendations for the treatment of BP in people with diabetes, which recommend a target systolic/diastolic BP of 130/80 mmHg with few exceptions, and a fixed combination of an RAAS blocker with a diuretic or a calcium channel blocker as first-line treatment.

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Title: Epigenetic Link Between Statin Therapy and Type 2 Diabetes. Citation: Diabetes care; Apr 2020; vol. 43 (no. 4); p. 875-884 Author(s): Ochoa-Rosales, Carolina; Portilla-Fernandez, Eliana; Nano, Jana; Wilson, Rory; Lehne, Benjamin; Mishra, Pashupati P; Gao, Xu; Ghanbari, Mohsen; Rueda-Ochoa, Oscar L; Juvinao-Quintero, Diana; Loh, Marie; Zhang, Weihua; Kooner, Jaspal S; Grabe, Hans J; Felix, Stephan B; Schöttker, Ben; Zhang, Yan; Gieger, Christian; Müller-Nurasyid, Martina; Heier, Margit; Peters, Annette; Lehtimäki, Terho; Teumer, Alexander; Brenner, Hermann; Waldenberger, Melanie; Ikram, M Arfan; van Meurs, Joyce B J; Franco, Oscar H; Voortman, Trudy; Chambers, John; Stricker, Bruno H; Muka, Taulant Objective: To investigate the role of epigenetics in statins' diabetogenic effect comparing DNA methylation (DNAm) between statin users and nonusers in an epigenome-wide association study in blood. Research Design and Methods: Five cohort studies' participants (n = 8,270) were classified as statin users when they were on statin therapy at the time of DNAm assessment with Illumina 450K or EPIC array or noncurrent users otherwise. Associations of DNAm with various outcomes like incident type 2 diabetes, plasma glucose, insulin, and insulin resistance (HOMA of insulin resistance [HOMA-IR]) as well as with gene expression were investigated. Results: Discovery (n = 6,820) and replication (n = 1,450) phases associated five DNAm sites with statin use: cg17901584 (1.12 × 10-25 [DHCR24]), cg10177197 (3.94 × 10-08 [DHCR24]), cg06500161 (2.67 × 10-23 [ABCG1]), cg27243685 (6.01 × 10-09 [ABCG1]), and cg05119988 (7.26 × 10-12 [SC4MOL]). Two sites were associated with at least one glycemic trait or type 2 diabetes. Higher cg06500161 methylation was associated with higher fasting glucose, insulin, HOMA-IR, and type 2 diabetes (odds ratio 1.34 [95% CI 1.22, 1.47]). Mediation analyses suggested that ABCG1 methylation partially mediates the effect of statins on high insulin and HOMA-IR. Gene expression analyses showed that statin exposure and ABCG1 methylation were associated with ABCG1 downregulation, suggesting epigenetic regulation of ABCG1 expression. Further, outcomes insulin and HOMA-IR were significantly associated with ABCG1 expression. Conclusions: This study sheds light on potential mechanisms linking statins with type 2 diabetes risk, providing evidence on DNAm partially mediating statins' effects on insulin traits. Further efforts shall disentangle the molecular mechanisms through which statins may induce DNAm changes, potentially leading to ABCG1 epigenetic regulation.

Title: With Coronary Artery Disease-A Persistent Challenge in Need of Substantial Improvement: A Report From ESC EORP EUROASPIRE V. Citation: Diabetes care; Apr 2020; vol. 43 (no. 4); p. 726-733 Author(s): Ferrannini, Giulia; De Bacquer, Dirk; De Backer, Guy; Kotseva, Kornelia; Mellbin, Linda; Wood, David; Rydén, Lars; EUROASPIRE V collaborators Objective: Dysglycemia, in this survey defined as impaired glucose tolerance (IGT) or type 2 diabetes, is common in patients with coronary artery disease (CAD) and associated with an unfavorable prognosis. This European survey investigated dysglycemia screening and risk factor management of patients with CAD in relation to standards of European guidelines for cardiovascular subjects. Research Design and Methods: The European Society of Cardiology's European Observational Research Programme (ESC EORP) European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V (2016-2017) included 8,261 CAD patients, aged 18-80 years, from 27 countries. If the glycemic state was unknown, patients underwent an oral glucose tolerance test (OGTT) and measurement of glycated hemoglobin A1c. Lifestyle, risk factors, and pharmacological management were investigated.

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Results: A total of 2,452 patients (29.7%) had known diabetes. OGTT was performed in 4,440 patients with unknown glycemic state, of whom 41.1% were dysglycemic. Without the OGTT, 30% of patients with type 2 diabetes and 70% of those with IGT would not have been detected. The presence of dysglycemia almost doubled from that self-reported to the true proportion after screening. Only approximately one-third of all coronary patients had completely normal glucose metabolism. Of patients with known diabetes, 31% had been advised to attend a diabetes clinic, and only 24% attended. Only 58% of dysglycemic patients were prescribed all cardioprotective drugs, and use of sodium-glucose cotransporter 2 inhibitors (3%) or glucagon-like peptide 1 receptor agonists (1%) was small. Conclusions: Urgent action is required for both screening and management of patients with CAD and dysglycemia, in the expectation of a substantial reduction in risk of further cardiovascular events and in complications of diabetes, as well as longer life expectancy.

Title: Risk of Major Adverse Cardiovascular Events, Severe Hypoglycemia, and All-Cause Mortality for Widely Used Antihyperglycemic Dual and Triple Therapies for Type 2 Diabetes Management: A Cohort Study of All Danish Users. Citation: Diabetes care; Apr 2020 Author(s): Jensen, Morten Hasselstrøm; Kjolby, Mads; Hejlesen, Ole; Jakobsen, Poul Erik; Vestergaard, Peter Objective: The vast number of antihyperglycemic medications and growing amount of evidence make clinical decision making difficult. The aim of this study was to investigate the safety of antihyperglycemic dual and triple therapies for type 2 diabetes management with respect to major adverse cardiovascular events, severe hypoglycemia, and all-cause mortality in a real-life clinical setting. Research Design And Methods: Cox regression models were constructed to analyze 20 years of data from the Danish National Patient Registry with respect to effect of the antihyperglycemic therapies on the three end points. Results: A total of 66,807 people with type 2 diabetes were treated with metformin (MET) including a combination of second- and third-line therapies. People on MET plus sulfonylurea (SU) had the highest risk of all end points, except for severe hypoglycemia, for which people on MET plus basal insulin (BASAL) had a higher risk. The lowest risk of major adverse cardiovascular events was seen for people on a regimen including a glucagon-like peptide 1 (GLP-1) receptor agonist. People treated with MET, GLP-1, and BASAL had a lower risk of all three end points than people treated with MET and BASAL, especially for severe hypoglycemia. The lowest risk of all three end points was, in general, seen for people treated with MET, sodium-glucose cotransporter 2 inhibitor, and GLP-1. Conclusions: Findings from this study do not support SU as the second-line treatment choice for patients with type 2 diabetes. Moreover, the results indicate that adding a GLP-1 for people treated with MET and BASAL could be considered, especially if those people suffer from severe hypoglycemia.

Title: Real-world outcomes of treatment with insulin glargine 300 U/mL versus standard-of-care in people with uncontrolled type 2 diabetes mellitus. Citation: Current medical research and opinion; Apr 2020; vol. 36 (no. 4); p. 571-581 Author(s): Freemantle, Nick; Mauricio, Didac; Giaccari, Andrea; Bailey, Timothy; Roussel, Ronan; Franco, Denise; Berthou, Baptiste; Pilorget, Valerie; Westerbacka, Jukka; Bosnyak, Zsolt; Bonnemaire, Mireille; Cali, Anna M G; Nguyên-Pascal, My-Liên; Penfornis, Alfred; Perez-Maraver, Manuel; Seufert, Jochen; Sullivan, Sean D; Wilding, John; Wysham, Carol; Davies, Melanie

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Objective: To compare real-world outcomes with newer (insulin glargine 300 U/mL; Gla-300) versus standard of care (SoC) basal insulins (BIs) in the REACH (insulin-naïve; NCT02967224) and REGAIN (basal insulin-treated; NCT02967211) studies in participants with uncontrolled type 2 diabetes (T2DM) in Europe and Brazil. Methods: In these open-label, parallel-group, pragmatic studies, patients (HbA1c > 7.0%) were randomized to Gla-300 or SoC BI for a 6-month treatment period (to demonstrate non-inferiority of Gla-300 vs SoC BIs for HbA1c change [non-inferiority margin 0.3%]) and a 6-month extension period (continuing with their assigned treatment). Insulin titration/other medication changes were at investigator/patient discretion post-randomization. Results: Overall, 703 patients were randomized to treatment in REACH (Gla-300, n = 352; SoC, n = 351) and 609 (Gla-300, n = 305, SoC, n = 304) in REGAIN. The primary outcome, non-inferiority of Gla-300 versus SoC for HbA1c change from baseline to month 6, was met in REACH (least squares [LS] mean difference 0.12% [95% CI -0.046 to 0.281]) but not REGAIN (LS mean difference 0.17% [0.015-0.329]); no between-treatment difference in HbA1c change was shown after 12 months in either study. BI dose increased minimally from baseline to 12 months in REACH (Gla-300, +0.17 U/kg; SoC, +0.15 U/kg) and REGAIN (Gla-300, +0.11 U/kg; SoC, +0.07 U/kg). Hypoglycemia incidence was low and similar between treatment arms in both studies. Conclusions: In both REACH and REGAIN, no differences in glycemic control or hypoglycemia outcomes with Gla-300 versus SoC BIs were seen over 12 months. However, the suboptimal insulin titration in REACH and REGAIN limits comparisons of outcomes between treatment arms and suggests that more titration instruction/support may be required for patients to fully derive the benefits from newer basal insulin formulations.

Title: Patient-reported outcomes in elderly patients with type 2 diabetes mellitus treated with dual oral therapy: a multicenter, observational study from Italy. Citation: Current medical research and opinion; Apr 2020; vol. 36 (no. 4); p. 555-562 Author(s): Lapolla, Annunziata; Genovese, Stefano; Giorgino, Francesco; Disoteo, Olga; Sartore, Giovanni; Bartezaghi, Marta; Del Prato, Stefano Objective: To assess patient-reported outcomes after two years of use of dual oral anti-diabetes drug (OAD) therapy in elderly people (≥65 years) with type 2 diabetes mellitus (T2DM) from Italy under real-life settings. Methods: 3-AGE was a prospective, non-interventional study in elderly people with T2DM inadequately controlled on metformin monotherapy (defined as glycated hemoglobin [HbA1c] 7.0-9.0%), in whom a second OAD was prescribed. Primary endpoint was to assess the physical and psychological symptoms associated with T2DM from baseline to 24 months using the Diabetes Symptom Check List revised (DSC-R) questionnaire. Patient's quality of life and health status, treatment satisfaction, consumption of healthcare resources, and physician satisfaction with treatment were also assessed (secondary endpoints) using validated questionnaires. Additionally, safety and clinical characteristics were also evaluated. Results: The mean age of the study population (N = 860) was 71.5 ± 5.2 years. Addition of a second OAD significantly (p < .0001) reduced the DSC-R score from baseline (0.73 ± 0.68) to both Months 12 and 24 (0.63 ± 0.59 and 0.61 ± 0.56), and HbA1c from baseline (7.72% ± 0.54%) to Month 12 (6.95% ± 0.82%). Adding a second OAD improved quality of life and health status (baseline, 71.31 ± 15.16 to Month 12, 74.49 ± 13.64; p < .0001), patient's treatment satisfaction (p < .0001), and consumption of healthcare resources per patient. Physicians expressed good satisfaction with patients' treatment (across efficacy, tolerability and compliance domains) at Month 12. Overall, 32 adverse reactions (in 24 patients) and four hypoglycemic episodes were reported during the 24 months. Conclusion: Addition of a second OAD improved physical and psychological symptoms associated with T2DM and was well tolerated in elderly people under real-life settings.

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Title: Plasma osteoprotegerin as a biomarker of poor glycaemic control that predicts progression of albuminuria in type 2 diabetes mellitus: A 3-year longitudinal cohort study. Citation: Diabetes Research & Clinical Practice; Mar 2020; vol. 161 Author(s): Moh, Angela Mei Chung; Pek, Sharon Li Ting; Liu, Jianjun; Wang, Jiexun; Subramaniam, Tavintharan; Ang, Keven; Sum, Chee Fang; Kwan, Pek Yee; Lee, Simon Biing Ming; Tang, Wern Ee; Lim, Su Chi Aims: Poor glycaemic control elevates the risk for vascular complications. Biomarkers for predicting susceptibility to glycaemic worsening are lacking. This 3-year prospective analysis assessed the utility of several circulating diabetes-related biomarkers for predicting loss of glycaemic control, and their contribution to albuminuria progression in type 2 diabetes mellitus (T2DM). Methods: T2DM subjects with adequately-controlled diabetes (HbA1c < 8%) at initial recruitment were analysed (N = 859). Baseline plasma levels of osteoprotegerin (OPG), C-reactive protein (CRP), adiponectin, intercellular-cell adhesion molecule-1, and vascular-cell adhesion molecule-1 were quantified using immunoassay. Definitions for development of uncontrolled diabetes and albuminuria progression were HbA1c ≥ 8.0% and increase in albuminuria category at follow-up, respectively. Results: At follow-up, 185 subjects developed uncontrolled diabetes. Higher baseline CRP and OPG levels were observed in the high-risk individuals, and predicted increased risk for developing uncontrolled diabetes. OPG, but not CRP, was associated with albuminuria progression after multivariable adjustment. The relationship was attenuated following adjustment for development of uncontrolled diabetes, which emerged as a significant associate. Mediation analysis revealed that loss of glycaemic control explained 64.5% of the relationship between OPG and albuminuria progression. Conclusions: OPG outperformed other diabetes-related biomarkers to be a potentially useful biomarker for predicting loss of glycaemic control and its associated albuminuria deterioration.

Title: Should sodium-glucose cotransporter-2 inhibitors be first-line treatment for patients with type 2 diabetes? Citation: Canadian Medical Association. Journal; Apr 2020; vol. 192 (no. 14); p. E375 Author(s): van Walraven, Carl, MD MSc Abstract: Van Walraven highlights the United Kingdom Prospective Diabetes Study (UKPDS). The study showed that attaining intensive glucose control in patients with newly diagnosed type 2 diabetes with metformin, sulfonylureas or insulin significantly decreased microvascular complication risks despite a small difference in glycosylated hemoglobin (HbA1c) of only 0.9% between treatment groups. In addition, the study showed that metformin significantly decreased all-cause mortality in those with obesity. Posttrial analyses of UKPDS found that intensive control by any treatment significantly decreased risks of diabetes-related outcomes, myocardial infarction and all-cause mortality. These results were attained despite identical HbA1c levels between treatment groups during posttrial monitoring. The Action to Control Cardiovascular Risk in Diabetes and Action in Diabetes and Vascular Disease: Preterax Diamicron Modified release Controlled Evaluation randomized controlled trials (both subsequently showed that intensive glucose control significantly decreased microvascular disease in those with long-standing type 2 diabetes. This research highlights the importance of good glucose control in the treatment of type 2 diabetes.

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Title: Stakeholders' perceptions and experiences of the National Health Service diabetes prevention programme in England: qualitative study with service users, intervention providers and deliverers, commissioners and referrers. Citation: BMC health services research; Apr 2020; vol. 20 (no. 1); p. 307 Author(s): Rodrigues, Angela M; Haste, Anna; Penn, Linda; Bell, Ruth; Summerbell, Carolyn; White, Martin; Adamson, Ashley J; Sniehotta, Falko F Background: The National Health Service diabetes prevention programme in England, (NHS DPP) aims to identify people at high risk of type 2 diabetes (T2D) and offer them a face-to-face, group-based, behaviour change intervention for at least 9 months. The NHS DPP was rolled out in phases. We aimed to elicit stakeholders' perceptions and experiences of the factors influencing implementation of, and participation in, the programme during the development phase. Methods: Individual, semi-structured telephone interviews were conducted with 50 purposively sampled stakeholders: service users (n = 20); programme commissioners (n = 7); referrers (n = 8); and intervention deliverers (n = 15). Topic guides were structured using a pragmatic, theory-informed approach. Analysis employed the framework method. Results: We identified factors that influenced participation: Risk communication at referral - stakeholders identified point of referral as a window of opportunity to offer brief advice, to provide an understanding of T2D risk and information about the programme; Perceived impact of the NHS DPP - service users highlighted the positive perceived impact on their behaviour change, the peer support provided by participating in the programme, the option to involve a relative, and the 'knock on' effect on others. Service users also voiced disappointment when blood test results still identified them at high risk after the programme; and Behavioural maintenance - participants highlighted the challenges linked to behavioural maintenance (e.g. discontinuation of active support). Factors influencing implementations were also identified: Case finding - stakeholders suggested that using community involvement to identify service users could increase reach and ensure that the workload was not solely on GP practices; Adaptability: intervention deliverers acknowledged the need to tailor advice to service users' preferences and needs; Accountability - the need to acknowledge who was responsible for what at different stages of the NHS DPP pathway; and Fidelity - stakeholders described procedures involved in monitoring service users' satisfaction, outcome data collection and quality assurance assessments. Conclusions: The NHS DPP offers an evidence-informed behavioural intervention for T2D prevention. Better risk communication specification could ensure consistency at the referral stage and improve participation in the NHS DPP intervention. Cultural adaptations and outreach strategies could ensure the NHS DPP contributes to reducing health inequalities.

Title: The Role of the Mediterranean Dietary Pattern on Metabolic Control of Patients with Diabetes Mellitus: A Narrative Review. Citation: Advances in experimental medicine and biology; Apr 2020 Author(s): Tosatti, Jéssica Abdo Gonçalves; Alves, Michelle Teodoro; Gomes, Karina Braga Abstract: Diabetes mellitus (DM) is a metabolic disorder characterised by hyperglycemia and abnormalities in carbohydrate, fat and protein metabolism. Several studies demonstrated that foods typical of the Mediterranean diet (MedDiet), including vegetables, fruits, oilseeds, extra virgin olive oil and fish, can promote health benefits for individuals at risk of or with type 2 diabetes (T2DM). In this review, we summarised randomised clinical trials, cohort studies, meta-analyses and systematic reviews that evaluated the effects of the MedDiet on metabolic control of T2DM. The data suggest that the MedDiet influences cardiovascular risk factors, including blood pressure, lipid profile, insulin resistance, inflammation and glucose metabolism, in T2DM patients. In conclusion, the MedDiet appears to protect patients from macro- and microangiopathy and should be considering in the management of diabetic patients.

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Title: GLP-1 receptor agonists in diabetes for stroke prevention: a systematic review and meta-analysis. Citation: Journal of neurology; Apr 2020 Author(s): Malhotra, Konark; Katsanos, Aristeidis H; Lambadiari, Vaia; Goyal, Nitin; Palaiodimou, Lina; Kosmidou, Maria; Krogias, Christos; Alexandrov, Andrei V; Tsivgoulis, Georgios Background: Randomized controlled clinical trials (RCT) have demonstrated varied efficacy of glucagon-like peptide-1 receptor (GLP-1R) agonists for cardiovascular outcomes. We sought to evaluate the efficacy and safety of GLP-1R agonists among patients with Type 2 diabetes mellitus (DM) for stroke prevention. Methods: We conducted a systematic review and meta-analysis of RCTs reporting the following outcomes among patients with Type 2 DM treated with GLP-1R agonists (vs. placebo): nonfatal or fatal strokes, all-cause or cardiovascular mortality, myocardial infarction (MI) and major adverse cardiovascular events (MACE). The protocol of our systematic review and meta-analysis was registered to the PROSPERO database. We pooled odds ratios (OR) using random-effect models, and assessed the heterogeneity using Cochran Q and I2 statistics. Results: We identified 8 RCTs, comprising 56,251 patients. In comparison to placebo, GLP-1R agonists reduced nonfatal strokes (OR 0.84; 95% CI 0.76-0.94, p = 0.002; I2 = 0%) and all strokes (OR 0.84; 95% CI 0.75-0.93, p = 0.001; I2 = 0%) by 16%. Overall, GLP-1R agonists reduced MACE by 13% (OR 0.87; 95% CI 0.81-0.94, p = 0.0003; I2 = 42%), cardiovascular mortality by 12% (OR 0.88; 95% CI 0.81-0.95; p = 0.002; I2 = 0%) and all-cause mortality by 12% (OR 0.88; 95% CI 0.82-0.95, p = 0.0007; I2 = 15%). Additional analyses demonstrated that GLP-1R agonists reduced the risk of incident MACE (OR 0.86; 95% CI 0.80-0.92; p < 0.0001; I2 = 0%) among patients with prior history of MI or nonfatal strokes. Conclusions: Among patients with type 2 DM, GLP-1R agonists are beneficial for primary stroke, MACE, and cardiovascular mortality prevention. Further RCTs are needed to evaluate their role for secondary stroke prevention.

Title: Differential glycaemic control with basal insulin glargine 300 U/mL versus degludec 100 U/mL according to kidney function in type 2 diabetes - a subanalysis from the BRIGHT trial. Citation: Diabetes, obesity & metabolism; Apr 2020 Author(s): Haluzík, Martin; Cheng, Alice; Müller-Wieland, Dirk; Westerbacka, Jukka; Bosnyak, Zsolt; Lauand, Felipe; Melas-Melt, Lydie; Karalliedde, Janaka; Rosenstock, Julio; Bolli, Geremia B Aims: Chronic kidney disease (CKD) challenges diabetes management and is associated with increased cardiovascular morbidity and mortality. We examined whether clinical outcomes with insulin glargine 300 U/mL (Gla-300) and insulin degludec 100 U/mL (IDeg-100) are affected by renal function in a pre-specified subgroup analysis from the BRIGHT trial. Materials and Methods: BRIGHT (NCT02738151) was a multicentre, open-label, randomised, active-controlled, two-arm, parallel-group, 24-week study in insulin-naïve uncontrolled type 2 diabetes (T2D). Participants were randomised 1:1 to evening Gla-300 (n=466) or IDeg-100 (n=463) and stratified based on baseline estimated glomerular filtration rate (eGFR) for this analysis. Results: Heterogeneity of treatment effect across renal function subgroups was observed (p=0.02), reflecting a greater mean HbA1c reduction from baseline to week 24 with Gla-300 versus IDeg-100 in the eGFR <60 mL/min/1.73 m2 subgroup (LS mean difference: -0.43 % [95% CI: -0.74 to -0.12 %]), while there were no differences in hypoglycaemia incidence or rates over 24 weeks in that subgroup. HbA1c reductions were similar between treatments in the other eGFR subgroups. However, heterogeneity was observed for annualised rates of anytime (24 h) or nocturnal (00:00-05:59 h) confirmed hypoglycaemia (≤70 mg/dL [≤3.9 mmol/L]) over 24 weeks showing less hypoglycaemia with Gla-300 versus IDeg-100 in the ≥90 mL/min/1.73 m2 .

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Conclusions: Kidney function seems to impact the glucose-lowering effects of Gla-300 versus IDeg-100 in insulin-naïve T2D. Greater HbA1c reductions with Gla-300 without increase in hypoglycaemia risk, were observed in patients with eGFR <60 mL/min/1.73 m2 . This article is protected by copyright. All rights reserved.

Title: Chronic kidney disease in type 2 diabetes: Implications for managing glycaemic control, cardiovascular and renal risk. Citation: Diabetes, obesity & metabolism; Apr 2020; vol. 22 Author(s): Stephens, Jeffrey W; Brown, Karen E; Min, Thinzar Abstract: This review examines the current literature relating to diabetes related kidney disease (DKD) and the optimal management of cardio-renal risk. DKD develops in approximately 40% of patients with type 2 diabetes mellitus. The mainstay of therapy is to reduce the progression of DKD by optimising hyperglycaemia, blood pressure, lipids and lifestyle. Evidence supports the role for renin-angiotensin system blockade in limiting the progression of DKD. Recent data from diabetes related cardiovascular outcome trials and renal specific trials have provided a novel insight on the additional benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in reducing the progression of DKD as well as cardiovascular risk. Lessons have been learnt from CREDENCE and there are expectations that DAPA-CKD and EMPA-KIDNEY will further support the benefits of SGLT2 inhibition in relation to DKD. As a consequence, international guidelines have been updated to reflect the positive benefits. In addition, novel steroidal mineralocorticoid receptor antagonists offer a potential role in future years. The review examines the current evidence and future approach to optimising outcomes for renal protection in patients with diabetes.

Title: Psychological interventions to improve glycemic control in adults with type 2 diabetes: a systematic review and meta-analysis. Citation: BMJ open diabetes research & care; Apr 2020; vol. 8 (no. 1) Author(s): Winkley, Kirsty; Upsher, Rebecca; Stahl, Daniel; Pollard, Daniel; Brennan, Alan; Heller, Simon R; Ismail, Khalida Abstract: The quality of evidence that psychological interventions are effective in improving glycemic control in adults with type 2 diabetes (T2D) is weak.We conducted a systematic review and meta-analysis of psychological interventions in T2D to assess whether their effectiveness in improving glycemic levels has improved over the past 30 years. We applied the protocol of a systematic review and aggregate meta-analysis conducted to January 2003. We added network meta-analysis (NMA) to compare intervention and control group type against usual care. MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, EMBASE, Cochrane Controlled Trials Database, Web of Science, and Dissertation Abstracts International were searched from January 2003 to July 2018. Only randomized controlled trials (RCT) of psychological interventions for adults with T2D reported in any language were included. The primary outcome was change in glycemic control (glycated hemoglobin (HbA1c) in mmol/mol). Data were extracted from study reports and authors were contacted for missing data.94 RCTs were eligible for inclusion in the systematic review since the last review. In 70 RCTs (n=14 796 participants) the pooled mean difference in HbA1c in those randomized to psychological intervention compared with control group was -0.19 (95% CI -0.25 to -0.12), equivalent to a reduction in HbA1c of 3.7 mmol/mol, with moderate heterogeneity across studies (I2=64.7%, p<0.001). NMA suggested the probability of intervention effectiveness is highest for self-help materials, cognitive-behavioral therapy, and counseling, compared with usual care. Limitations of this study include that there is a possibility that some studies may have been missed if diabetes did not appear in the title or abstract.The effectiveness of psychological interventions for

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adults with T2D have minimal clinical benefit in improving glycemic control. PROSPERO REGISTRATION NUMBER: CRD42016033619.

Title: Aspirin Versus Clopidogrel Monotherapy for the Secondary Prevention of Recurrent Cerebrovascular Attack Following Previous Ischemic Stroke in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Citation: Diabetes therapy : research, treatment and education of diabetes and related disorders; Mar 2020 Author(s): Qin, Zu-Ye; Yang, Xiu-Fang; Lian, Chao-Ying; Yan, Xun-Jin; Lin, Min-Shi; Bundhun, Pravesh Kumar; Lao, You-Yi Introduction: Type 2 diabetes mellitus (T2DM) and stroke are two different diseases, but have many aspects in common. Aspirin is recommended as an initial treatment for the secondary prevention of recurrent ischemic stroke in patients with T2DM. However, clopidogrel is an oral antiplatelet drug that might be another choice in case of aspirin intolerance. In this analysis, we aimed to systematically compare aspirin versus clopidogrel monotherapy for the secondary prevention of recurrent cerebrovascular attack following previous ischemic stroke in patients with T2DM. Methods: Online medical databases including Web of Science, MEDLINE, Cochrane central, EMBASE and http://www.ClinicalTrials.com were searched for published articles that satisfied the inclusion and exclusion criteria of this study. Recurrent stroke, fatal stroke, cerebral hemorrhage, myocardial infarction and mortality were considered the main end points in these patients with T2DM. RevMan 5.3 software was used to statistically analyze the data representing each subgroup. Risk ratios (RRs) with 95% confidence intervals (CIs) were used to represent the results following analysis. Results: A total of 9218 participants with T2DM who were previously affected by ischemic stroke were included in this analysis, whereby 4917 were assigned to aspirin and 4301 to clopidogrel. This current analysis showed that there was no significant difference in recurrent stroke rate (RR: 0.79, 95% CI: 0.61-1.02; P = 0.07) observed with aspirin versus clopidogrel in these patients with T2DM. The risk of fatal stroke (RR: 0.88, 95% CI: 0.39-1.98; P = 0.76), cerebral hemorrhage (RR: 0.65, 95% CI: 0.38-1.11; P = 0.12), myocardial infarction (RR: 0.88, 95% CI: 0.43-1.79; P = 0.71) and mortality (RR: 1.07, 95% CI: 0.90-1.27; P = 0.44) were also similarly manifested. Conclusion: Clopidogrel monotherapy was neither inferior nor superior to aspirin monotherapy for the secondary prevention of recurrent cerebrovascular attack following previous ischemic stroke in patients with T2DM. Hence, clopidogrel or aspirin monotherapy is equally safe and effective in these patients with T2DM.

Title: Availability and analytical quality of hemoglobin A1c point-of-care testing in general practitioners' offices are associated with better glycemic control in type 2 diabetes. Citation: Clinical chemistry and laboratory medicine; Mar 2020 Author(s): Tollånes, Mette C; Jenum, Anne K; Berg, Tore Julsrud; Løvaas, Karianne F; Cooper, John G; Sandberg, Sverre Background: It is not clear if point-of-care (POC) testing for hemoglobin A1c (HbA1c) is associated with glycemic control in type 2 diabetes. Methods: In this cross-sectional study, we linked general practitioner (GP) data on 22,778 Norwegian type 2 diabetes patients to data from the Norwegian Organization for Quality Improvement of Laboratory Examinations. We used general and generalized linear mixed models to investigate if GP offices' availability (yes/no) and analytical quality of HbA1c POC testing (average yearly "trueness score", 0-4), as well as frequency of participation in HbA1c external quality assurance (EQA) surveys, were associated with patients' HbA1c levels during 2014-2017.

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Results: Twenty-eight out of 393 GP offices (7%) did not perform HbA1c POC testing. After adjusting for confounders, their patients had on average 0.15% higher HbA1c levels (95% confidence interval (0.04-0.27) (1.7 mmol/mol [0.5-2.9]). GP offices participating in one or two yearly HbA1c EQA surveys, rather than the maximum of four, had patients with on average 0.17% higher HbA1c levels (0.06, 0.28) (1.8 mmol/mol [0.6, 3.1]). For each unit increase in the GP offices' HbA1c POC analytical trueness score, the patients' HbA1c levels were lower by 0.04% HbA1c (-0.09, -0.001) (-0.5 mmol/mol [-1.0, -0.01]). Conclusions: Novel use of validated patient data in combination with laboratory EQA data showed that patients consulting GPs in offices that perform HbA1c POC testing, participate in HbA1c EQA surveys, and maintain good analytical quality have lower HbA1c levels. Accurate HbA1c POC results, available during consultations, may improve diabetes care.

Title: The burden of type 2 diabetes in Europe: Current and future aspects of insulin treatment from patient and healthcare spending perspectives. Citation: Diabetes Research & Clinical Practice; Mar 2020; vol. 161 Author(s): Ceriello, Antonio; deValk, Harold W.; Guerci, Bruno; Haak, Thomas; Owens, David; Canobbio, Michela; Fritzen, Katharina; Stautner, Constantin; Schnell, Oliver Abstract: Due to the progressive nature of type 2 diabetes (T2DM), initiation of insulin therapy is very likely in the disease continuum. This article aims at highlighting the current situation with regard to insulin therapy in people with T2DM in Europe and at presenting the associated unmet need. Challenges for both people with T2DM and healthcare professionals include clinical inertia also derived from fear of hypoglycaemia, weight gain and injections as well as increased need for a comprehensive diabetes management. We compare national and international guidelines and recommendations for the initiation and intensification of insulin therapy with the real-world situation in six European countries, demonstrating that glycaemic targets are only met in a minority of people with T2DM on insulin therapy. Furthermore, this work evaluates currently recorded numbers of people with T2DM treated with insulin in Europe, the proportion not achieving the stated glycaemic targets and thus in need to enhance insulin therapy e.g. by a change in means of insulin delivery including, but not limited to, insulin pens, wearable mealtime insulin delivery patches, patch pumps, and conventional insulin pumps with continuous subcutaneous insulin infusion.

Title: Advances in type 2 diabetes therapy: a focus on cardiovascular and renal outcomes. Citation: Medical Journal of Australia; Feb 2020; vol. 212 (no. 3); p. 133-139 Author(s): Libianto, Renata; Davis, Timothy ME; Ekinci, Elif I Abstract: Treatment options for type 2 diabetes have expanded. While metformin remains the first line treatment in most cases, choices for second line treatment now extend beyond sulfonylureas and include the sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP1) receptor agonists, and dipeptidyl peptidase 4 (DPP4) inhibitors. SGLT2 inhibitors are recommended for people with atherosclerotic cardiovascular disease, heart failure or kidney disease. Diabetic ketoacidosis is an uncommon but important side effect; its occurrence can be minimised with appropriate patient education and management, especially during perioperative periods and times of illness. GLP1 receptor agonists are recommended for people with atherosclerotic cardiovascular disease. Gastrointestinal side effects are common but are less prominent with the longer acting agents and can be minimised with slow titration of the shorter acting agents. DPP4 inhibitors are generally well tolerated, but alogliptin and saxagliptin should be used with caution in people with risk factors for heart failure. To optimise the management of type 2 diabetes, clinicians need to be aware of the pharmacological characteristics of each class of blood glucose-lowering medications and of the effect on cardiovascular health and renal function, balanced by potential adverse effects. Medications

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that have cardiovascular or renal benefits should be prescribed for patients with these comorbidities, and this is reflected in recent international guidelines.

Title: Cardiovascular risk following metformin treatment in patients with type 2 diabetes mellitus: Results from meta-analysis. Citation: Diabetes Research & Clinical Practice; Feb 2020; vol. 160 Author(s): Zhang, Kui; Yang, Wenxing; Dai, Hao; Deng, Zhenhua Aim: Pharmacologic therapy for T2DM has proven benefits in terms of reducing elevated blood glucose levels and reducing microvascular complications. However, the impact of metformin on adverse cardiovascular outcomes and cardiovascular mortality is less clear. We carried out this meta-analysis on all published studies to estimate the overall cardiovascular risk following metformin treatment in patients with T2DM. Methods: We searched the PubMed, Embase and CNKI (China National Knowledge Infrastructure) databases for all articles. The odds ratio (OR) corresponding to the 95% confidence interval (95% CI) was used to assess the cardiovascular risk following metformin treatment in patients with T2DM. The statistical heterogeneity among studies was assessed with the Q-test and I2 statistics. Results: We collected 16 studies including 25 comparisons with 1,160,254 patients of type 2 diabetes mellitus and 701,843 patients of T2DM following metformin treatment. Our results found statistical evidence of significantly decreased cardiovascular risk to be associated with following treatment with metformin in patients with type 2 diabetes mellitus (OR = 0.57, 95% CI = 0.48-0.68) (shown in Table 1 and Fig. 2), both with the mortality (OR = 0.44, 95% CI = 0.34-0.57) and incidence (OR = 0.73, 95% CI = 0.59-0.90). Conclusions: Our meta-analysis indicated that following metformin treatment in patients with T2DM was associated with decreased cardiovascular risk, both with the mortality and incidence. However, the heterogeneity among studies may potentially affect the final results.

Title: Ethnic differences in the severity and clinical management of type 2 diabetes at time of diagnosis: A cohort study in the UK Clinical Practice Research Datalink. Citation: Diabetes Research & Clinical Practice; Feb 2020; vol. 160 Author(s): Mathur, R.; Palla, L.; Farmer, R.E.; Chaturvedi, N.; Smeeth, L. Aims: To characterize ethnic differences in the severity and clinical management of type 2 diabetes at initial diagnosis. Methods: An observational cohort study of 179,886 people with incident type 2 diabetes between 2004 and 2017 in the Clinical Practice Research Datalink was undertaken; 63.4% of the cohort were of white ethnicity, 3.9% south Asian, and 1.6% black. Ethnic differences in clinical profile at diagnosis, consultation rates, and risk factor recording were derived from linear and logistic regression. Cox-proportional hazards regression was used to determine ethnic differences in time to initiation of therapeutic and non-therapeutic management following diagnosis. All analyses adjusted for age, sex, deprivation, and clustering by practice. Results: In the 12 months prior to diagnosis, non-white groups had fewer consultations compared to white groups, but risk factor recording was better than or equivalent to white groups for 9/10 risk factors for south Asian groups and 8/10 risk factors for black groups (p < 0.002). Blood pressure, BMI, cholesterol, eGFR, and CVD risk levels were more favourable in non-white groups, and prevalence of macrovascular disease was significantly lower (p < 0.003). Time to initiation of antidiabetic treatment and first risk assessment was faster in non-white groups relative to white groups, while time to risk factor measurement and diabetes review was slower.

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Conclusions: We find limited evidence of systematic ethnic inequalities around the time of type 2 diabetes diagnosis. Ethnic disparities in downstream consequences may relate to genetic risk factors, or manifest later in the care pathway, potentially in relation to long-term risk factor control. Sources Used: The following databases are used in the creation of this bulletin: BNI, CINAHL, EMBASE and Medline. Disclaimer: The results of your literature search are based on the request that you made, and consist of a list of references, some with abstracts. Royal United Hospital Bath Healthcare Library will endeavour to use the best, most appropriate and most recent sources available to it, but accepts no liability for the information retrieved, which is subject to the content and accuracy of databases, and the limitations of the search process. The library assumes no liability for the interpretation or application of these results, which are not intended to provide advice or recommendations on patient care.