Diabetes Current Awareness Bulletin February 2020

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*Image attribution, see final page for details. General Articles Title: A roundup of the simplest mobile phone uses in diabetes management Citation: Diabetes Research and Clinical Practice 158, 107895. Author(s): Dastjerdi M.S. Abstract: In this short commentary, we will discuss the simple uses of mobile phones and how they can contribute to the communication between patients and health professional providers.

Co-­‐morbidities (find here cardiovascular, kidney disease, neuropathy, diabetic retinopathy etc) Title: Thyroid Dysfunction and Type 2 Diabetes Mellitus: Screening Strategies and Implications for Management

Citation: Diabetes Therapy 10(6), 2035-­‐44. Author(s): Kalra S. Abstract: This review summarizes current knowledge about coexistent T2DM and TD and discusses enhanced screening recommendations as well as clinical implications for the management of these two endocrinopathies.

Cardiovascular Disease Title: Achievement of cardiovascular risk factor targets according to sex and previous history of cardiovascular disease in type 2 diabetes: A population-­‐based study Citation: Journal of Diabetes and Its Complications 33(12), 107445. Author(s): Galbete A. Abstract: The main objective was to assess, using real-­‐practice primary care records, the degree of control of cardiovascular risk factor targets. Records were stratified by the presence of previous history or

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cardiovascular disease (CVD), and sex differences in the fulfillment profile were analyzed. Available with your NHS OpenAthens account

Title: Cardiac Autonomic Neuropathy in Obesity, the Metabolic Syndrome and Prediabetes: A Narrative Review

Citation: Diabetes Therapy 10(6), 1995-­‐2021. Author(s): Williams S.M. Abstract: This article reviews the literature on CAN in obesity, pre-­‐DM and MetS, to help determine a rationale for screening, early intervention treatment and formulate future research questions in this highly prevalent condition.

Title: Effect of Once-­‐Weekly Exenatide in Patients With Type 2 Diabetes Mellitus With and Without Heart

Failure and Heart Failure-­‐Related Outcomes: Insights From the EXSCEL Trial.

Citation: Circulation 2019;140(20):1613-­‐1622. Author(s): Fudim M. Abstract: In EXSCEL, the use of EQW in patients with or without HF was well tolerated, but benefits of EQW on

reduction in all-­‐cause death and first hospitalization for HF were attenuated in patients with baseline HF.

Title: Glucagon-­‐like peptide-­‐1 receptor agonists and cardiovascular outcomes in patients with and

without prior cardiovascular events: An updated meta-­‐analysis and subgroup analysis of randomized controlled trials. Citation: Diabetes Obesity and Metabolism 2019;:10.1111/dom.13888. Author(s): Mannucci E. Abstract: GLP-­‐1RAs are associated with a reduction in cardiovascular morbidity and mortality in high-­‐risk patients with diabetes. This effect does not appear to be moderated by gender or body mass index. The possibility of

different effects of GLP-­‐1RAs between patients in primary and secondary prevention merits further investigation.

Title: Prevalence of Established Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus in the UK

Citation: Diabetes Therapy 10(6), 2131-­‐7. Author(s): Lautsch D. Abstract: SGLT2 inhibitors appear to be particularly beneficial in patients with heart failure. As recent data for the UK are lacking, we undertook to identify the percentage of T2DM patients with eCVD and heart failure in the UK.

Diabetic Neuropathy Title: Diabetic peripheral neuropathy: advances in diagnosis and strategies for screening and early intervention

Citation: The Lancet Diabetes & Endocrinology 7(12), pp.938-­‐48. Author(s): Selvarajah D. Abstract: In this Review, we appraise innovative point-­‐of-­‐care devices that enable the early diagnosis of DPN

and assess the evidence for early risk factor-­‐based management strategies to reduce the incidence and slow the progression of DPN. We also propose a framework for screening and early multifactorial interventions as the best prospect for preventing or halting DPN and its devastating sequelae.

Title: Sex differences in neuropathy & neuropathic pain: A brief report from the Phase 2 Canadian Study of Longevity in Type 1 Diabetes Citation: Journal of Diabetes and Its Complications 33(12), 107397. Author(s): Cardinez N. Abstract: Despite better neuropathy measures in females compared to males, we confirmed a trend towards higher neuropathic pain in females.

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Eye Diseases Title: Advances in the treatment of diabetic retinopathy Citation: Journal of Diabetes and Its Complications 33(12), 107417. Author(s): Author(s): Singh R.P. Abstract: Vascular endothelial growth factor (VEGF)-­‐A is upregulated in the diabetic eye, and has been identified as a key driver of DR pathogenesis. With this perspective, we review the published phase III clinical trial data of

anti-­‐VEGF therapies approved for the treatment of DR in the United States.

Title: Diabetic retinopathy as an independent predictor of subclinical cardiovascular disease: baseline results of the PRECISED study Citation: BMJ Open Diabetes Research and Care 2019;7:e000845. Author(s): Simo R. Abstract: The presence and degree of DR is independently associated with subclinical CVD in type 2 diabetic patients. Our results lead us to propose a rationalized screening for coronary artery disease in type 2 diabetes based on prioritizing patients with DR, particularly those with moderate–severe degree.

Title: Fluocinolone acetonide intravitreal implant for treating chronic diabetic macular oedema in phakic eyes after an inadequate response to previous therapy. Citation: National Institute for Health and Care Excellence (NICE);2019. https://www.nice.org.uk/guidance/ta613 Abstract: 1 Recommendations. 1.1 Fluocinolone acetonide intravitreal implant is not recommended as an option for treating chronic diabetic macular oedema that is insufficiently responsive to available therapies in an eye with a natural lens (phakic eye). 1.2 This recommendation is not intended to affect treatment with fluocinolone acetonide intravitreal implant that was started in the NHS before this guidance was published.

Kidney Disease Title: Isolated high home systolic blood pressure in patients with type 2 diabetes is a prognostic factor for

the development of diabetic nephropathy: KAMOGAWA-­‐HBP study Citation: Diabetes Research and Clinical Practice 158, 107920. Author(s): Kitagawa N. Abstract: IH-­‐HSBP in patients with type 2 diabetes with normoalbuminuria was prognostic factor for the

development of diabetic nephropathy. We should pay more attention to IH-­‐HSBP to prevent the development of diabetic nephropathy.

Title: Validation of a protein biomarker test for predicting renal decline in type 2 diabetes: The Fremantle Diabetes Study Phase II Citation: Journal of Diabetes and Its Complications 33(12), 107406. Author(s): Peters K.E. Abstract: The combination of readily available clinical and laboratory features and the PromarkerD biomarkers (apoA4, CD5L, IGFBP3) proved an accurate prognostic test for future renal decline in an independent validation cohort of people with type 2 diabetes.

Complications (find here atherosclerosis, claudication, diabetic foot, ulcers etc) Diabetic Foot Title: Adherence to guideline recommended medical therapies in type 2 diabetic patients with chronic critical limb ischemia Citation: Diabetes Research and Clinical Practice 158, 107898. Author(s): Iacopi E.

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Abstract: The aim of this study was to evaluate the adherence to guideline recommended medical therapies in type 2 diabetic patients with chronic critical limb ischemia (CCLI).

Title: Hyperbaric oxygen therapy for nonischemic diabetic ulcers: A systematic review. Citation: Wound Repair and Regeneration 2019;:doi: 10.1111/wrr.12776. Author(s): Lalieu RC. Abstract: The current evidence suggests that hyperbaric oxygen therapy does not accelerate wound healing and does not prevent major or minor amputations in patients with a diabetic foot ulcer without peripheral arterial occlusive disease. Based on the available evidence, routine clinical use of this therapy cannot be recommended. However, the available research for this specific subgroup of patients is scarce, and physicians should counsel patients on expected risks and benefits.

Title: Is There a Role for Informal Caregivers in the Management of Diabetic Foot Ulcers? A Narrative Review

Citation: Diabetes Therapy 10(6), 2025-­‐33. Author(s): Messenger G. Abstract: This narrative review aims to explore how ICGs can benefit DFU management with applicability to different healthcare setups while benefiting from established experience in the care of other chronic health conditions.

Title: Risk factors for major amputation in hospitalized diabetic patients with forefoot ulcers Citation: Diabetes Research and Clinical Practice 158, 107905. Author(s): Moon K. Abstract: Risk factors for major amputation in patients hospitalized with diabetic forefoot ulcers include male gender, increased magnesium, increased platelet levels, and low levels of HbA1c.

Diabetes and pregnancy Articles Title: Prevention of gestational diabetes mellitus in overweight or obese pregnant women: A network

meta-­‐analysis Citation: Diabetes Research and Clinical Practice 158, 107924. Author(s): Chatzakis C. Abstract: Interventions aiming to prevent the development of GDM in overweight/obese women are not effective, when applied during pregnancy.

Title: Screening for gestational diabetes mellitus – Can we use the 50-­‐g glucose challenge test of the previous pregnancy? Citation: Diabetes Research and Clinical Practice 158, 107913. Author(s): Rottenstreich M. Abstract: GCT results in previous pregnancy is associated with GDM incidence in the subsequent pregnancy. Future prospective studies are warranted to better delineate the best screening approach for this subset of patients.

Title: The effect of smoking on the risk of gestational diabetes mellitus and the OGTT profile during pregnancy Citation: Diabetes Research and Clinical Practice 158, 107901. Author(s): Konstantakou P. Abstract: The present study did not show any correlation between smoking and GDM risk. However, OGTT profile and HbA1c differed according to smoking status in women with and without GDM.

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Title: Timing of delivery in women with pre-­‐pregnancy diabetes mellitus: a population-­‐based study Citation: BMJ Open Diabetes Research and Care 2019;7:e000758. Author(s): Brown M. Abstract: In pregnant women with PDM, IOL at 38

0/7–38

6/7 weeks was not associated with a higher risk of

cesarean delivery, compared with expectant management, but was associated with a higher risk of certain adverse neonatal outcomes.

Title: Future of information technology and telecommunication in type 1 diabetes clinical care: results of an online survey Citation: BMJ Open Diabetes Research and Care 2019;7:e000917. Author(s): Haluza D. Abstract: This online survey identified a highly ICT-­‐astute group of people with type 1 diabetes, already using technology for insulin delivery, for whom online supported clinical diabetes care would be a viable and welcomed option.

Title: Contribution of type 2 diabetes to all-­‐cause mortality, cardiovascular disease incidence and cancer incidence in white Europeans and South Asians: findings from the UK Biobank population-

­‐based cohort study Citation: BMJ Open Diabetes Research and Care 2019;7:e000765. Author(s): Muilwijk, M. Abstract: Although T2D was associated with a higher risk for all-­‐cause mortality and CVD incidence and mortality, in both white Europeans and South Asians, the risk experienced by South Asians with T2D was higher than their white European counterparts.

Title: Effectiveness of diabetes self-­‐management education and support via a smartphone application in insulin-­‐treated patients with type 2 diabetes: results of a randomized controlled trial (TRIGGER study) Citation: BMJ Open Diabetes Research and Care 2019;7:e000981. Author(s): Boels A.M. Abstract: This smartphone app providing diabetes self-­‐management education and support had small and clinically not relevant effects. Apps should be more personalized and target individuals who think the app will be useful for them.

Title: Gastric bypass versus sleeve gastrectomy in patients with type 2 diabetes (Oseberg): a single-

­‐centre, triple-­‐blind, randomised controlled trial

Citation: The Lancet Diabetes & Endocrinology 7(12), pp.912-­‐24. Author(s): Hofso D. Abstract: Gastric bypass was found to be superior to sleeve gastrectomy for remission of type 2 diabetes at 1 year

after surgery, and the two procedures had a similar beneficial effect on β-­‐cell function. The use of gastric bypass as the preferred bariatric procedure for patients with obesity and type 2 diabetes could improve diabetes care and reduce related societal costs.

Title: Long-­‐term effects of intensive multifactorial therapy in individuals with screen-­‐detected type

2 diabetes in primary care: 10-­‐year follow-­‐up of the ADDITION-­‐Europe cluster-­‐randomised trial

Citation: The Lancet Diabetes & Endocrinology 7(12), pp.925-­‐37. Author(s): Griffin S.J. Abstract: Sustained reductions in glycaemia and related cardiovascular risk factors over 10 years among people

with screen-­‐detected diabetes managed in primary care are achievable. The differences in prescribed treatment and cardiovascular risk factors in the 5 years following diagnosis were not maintained at 10 years, and the

difference in cardiovascular events and mortality remained non-­‐significant.

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Title: Maternal vs paternal diabetes: The parental history is different in younger onset versus older onset type 2 diabetes Citation: Journal of Diabetes and Its Complications 33(12), 107440. Author(s): Middleton T.L. Abstract: Overall, our results demonstrate a consistent maternal excess of diabetes which could be consistent with an underlying epigenetic effect. However, the differential between maternal and paternal history is significantly lower

in the young-­‐onset group. Earlier emergence of type 2 diabetes may therefore reflect a different interaction and impact of genetic and environmental factors.

Title: Patient-­‐centred care in type 2 diabetes mellitus – Key aspects of PDM-­‐ProValue are reflected in the 2018 ADA/EASD consensus report Citation: Diabetes Research and Clinical Practice 158, 107897. Author(s): Fritzen K. Abstract: In this comparative review, we identified the standardised decision cycle as well as individualised

patient assessment as the overarching elements of the ADA/EASD consensus report and the PDM-­‐ ProValue study.

Title: Type 2 Diabetes Mellitus and Menopausal Hormone Therapy: An Update

Citation: Diabetes Therapy 10 (6), 2313-­‐20. Author(s): Paschou S.A. Citation: T2DM was considered in the past as a cardiovascular disease (CVD) equivalent, which would suggest that women with T2DM should not receive MHT. This notion may still deter many clinicians from prescribing MHT to these patients. However, nowadays there is strong evidence to support an individualised approach after careful evaluation of CVD risk.

Diabetic subtypes (genetic) Articles Title: Hypoglycemia and antihyperglycemic treatment in adult MODY patients – A systematic review of literature Citation: Diabetes Research and Clinical Practice 158, 107914. Author(s): Urbanova J. Abstract: This review aims to analyze clinical studies and case reports concerning hypoglycemia associated with antihyperglycemic treatment in adult MODY patients.

Title: Patterns of postmeal insulin secretion in individuals with sulfonylurea-­‐treated KCNJ11

neonatal diabetes show predominance of non-­‐KATP-­‐channel pathways Citation: BMJ Open Diabetes Research and Care 2019;7:e000721. Author(s): Bowman P. Abstract: Individuals with sulfonylurea-­‐treated KCNJ11 PNDM produce similar levels of insulin in response to both carbohydrate and protein/fat meals despite carbohydrate resulting in much higher glucose levels and protein/fat resulting in relatively low glucose levels. This suggests in an inability to modulate insulin secretion in response to

glucose levels, consistent with a dependence on non-­‐KATP pathways for insulin secretion.

Glucose monitoring and control Articles Title: Impact of Carbohydrate on Glucose Variability in Patients with Type 1 Diabetes Assessed Through Professional Continuous Glucose Monitoring: A Retrospective Study Citation: Diabetes Therapy 10 (6), 2289-­‐2304.

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Author(s): Lin Y.H. Abstract: The aim of this study was to objectively analyze the correlation between dietary components and blood glucose variation by means of continuous glucose monitoring (CGM).

Title: Improved well-­‐being and decreased disease burden after 1-­‐year use of flash glucose

monitoring (FLARE-­‐NL4) Citation: BMJ Open Diabetes Research and Care 2019;7:e000809. Author(s): Fokkert M. Abstract: Real world data demonstrate that use of FSL-­‐FGM results in improved well-­‐being and decreased disease burden, as well as improvement of glycemic control.

Title: Relationship between glucose variability evaluated by continuous glucose monitoring and

clinical factors, including glucagon-­‐stimulated insulin secretion in patients with type 2 diabetes Citation: Diabetes Research and Clinical Practice 158, 107904. Author(s): Ohara M. Abstract: These results suggest that ΔCPR correlated with stability of glycemic control, whereas poorly controlled

diabetes is associated with increase in glucose variability. α-­‐glucosidase inhibitors may be superior to sulfonylureas in reducing the glucose variability in T2DM.

Title: RT-­‐CGM in adults with type 1 diabetes improves both glycaemic and patient-­‐reported outcomes, but independent of each other Citation: Diabetes Research and Clinical Practice 158, 107910. Author(s): Nefs G. Abstract: People with more suboptimal HbA 1c and PRO values appear to benefit most from RT-­‐CGM. Given the lack of association between improvements in medical outcomes and PROs, both should be included in evaluations of RT-­‐CGM therapy on an individual level.

Hypoglycaemia Articles

Title: Family Members: The Forgotten Players in the Diabetes Care Team (The TALK-­‐HYPO Study) Citation: Diabetes Therapy 10 (6), 2305-­‐11.

Author(s): Ratzki-­‐Leewing A. Abstract: Hypoglycemia can present a burden on the lives of family members of PWDs. Conversations about hypoglycemia, facilitated by a healthcare professional, may reduce this burden and hypoglycemia risk.

Title: Preference for Subcutaneously Administered Low-­‐Dose Glucagon Versus Orally Administered Glucose for Treatment of Mild Hypoglycemia: A Prospective Survey Study Citation: Diabetes Therapy 10 (6), 2107-­‐13. Author(s): Tetzschner R. Abstract: Intensive insulin treatment for type 1 diabetes is associated with high risk of mild hypoglycemia. Mild hypoglycemia is usually treated orally with glucose, which may contribute to weight gain. Subcutaneous injection of

low-­‐dose glucagon may be a new treatment option for some occasions of mild hypoglycemia in individuals aiming for optimal glycemic control without gaining weight. We investigated under which occasions patients were interested

to use low-­‐dose glucagon.

Title: Effect of Liraglutide on Times in Glycaemic Ranges as Assessed by CGM for Type 2 Diabetes Patients Treated With Multiple Daily Insulin Injections Citation: Diabetes Therapy 10 (6), 2115-­‐30.

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Author(s): Sofizadeh S. Abstract: For type 2 diabetes patients initially treated with MDI, introducing liraglutide had a beneficial effect on

glucose profiles estimated by masked CGM. Mean glucose level, glycaemic variability, C-­‐peptide, and proinsulin level influenced the risk of hypoglycaemia in this population.

Title: Improving Type 2 Diabetes Management in General Practice Using a Second-­‐Generation Basal Insulin Analogue Insulin Glargine 300 U/mL: A Practical Guide. Citation: Diabetes Therapy 10 (6), 1987-­‐94. Author(s): Deed G. Abstract: 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.

Title: Key factors for overcoming psychological insulin resistance: an examination of patient perspectives through content analysis Citation: BMJ Open Diabetes Research and Care 2019;7:e000723. Author(s): Stuckey H. Abstract: Based on these themes, two actionable strategies are suggested for HCPs to help people with psychological insulin resistance: (1) demonstrate the injection process and discuss negative perceptions of insulin as well as potential benefits; (2) offer autonomy in a person-­‐centred collaborative approach, but provide support and accessibility to address concerns. These findings help HCPs to better understand ways in which they can engage reluctant people with T2D with specific strategies.

Title: When should fixed ratio basal insulin/glucagon-­‐like peptide-­‐1 receptor agonists combination products be considered? Citation: Journal of Diabetes and Its Complications 33(12), 107473. Author(s): David J. and Fonseca V. Abstract: Review of combination treatment with existing fixed doses of basal insulin with GLP1 RA opens door for further clinical trials for other dose combinations that can be used, particularly for patients who need higher doses of insulin.

Management of diabetes (diet, exercise, lifestyle) Diet Title: Comparison of Group Medical Visits Combined With Intensive Weight Management vs Group Medical Visits Alone for Glycemia in Patients With Type 2 Diabetes: A Noninferiority Randomized Clinical Trial. Citation: JAMA Internal Medicine 2019;: doi: 10.1001/jamainternmed.2019.4802.. Author(s): Yancy WS Jr. Abstract: In GMVs for diabetes, addition of WM using a low-­‐carbohydrate diet was noninferior for lowering HbA1c levels compared with conventional medication management and showed advantages in other clinically important outcomes.

Exercise Title: Rationale and methods for the Exercise for Type 1 Diabetes Education program: a pilot randomized controlled trial of an education program to support adults with type 1 diabetes mellitus (T1DM) to undertake exercise Citation: BMJ Open Diabetes Research and Care 2019;7:e000693. Author(s): Narendran P.

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Abstract: This article outlines the protocol for a pilot RCT to develop a program of education that will support adults with T1DM to undertake safe and effective exercise. This is accompanied by training for HCPs to deliver this educational intervention. Successful completion of this program of work will address some of the barriers to exercise in adults with T1DM, and should facilitate an increase in exercise for this group of people.

Lifestyle Title: Supervised lifestyle intervention for people with metabolic syndrome improves outcomes and reduces individual risk factors of metabolic syndrome: A systematic review and meta-­‐analysis. Citation: Metabolism 2019;:doi: 10.1016/j.metabol.2019.153988. Author(s): van Namen M. Abstract: There is low to moderate quality evidence that supervised multifaceted lifestyle intervention improves multiple risk factors of metabolic syndrome, as well as reducing prevalence of the disease. Health services should consider implementing lifestyle intervention programs for people with metabolic syndrome to improve health outcomes and prevent progression to chronic disease.

Mental health and diabetes Articles

Title: Factors influencing the effect of mindfulness-­‐based interventions on diabetes distress: a meta-­‐analysis Citation: BMJ Open Diabetes Research and Care 2019;7:e000757. Author(s): Guo J. Abstract: This meta-­‐analysis provides further evidence to support the use of MBIs in reducing diabetes distress in adults with diabetes. Factors influencing the effect of MBIs on diabetes distress have been identified, including

diabetes distress status at baseline, group-­‐based interventions, and using an MBSR therapy. Incorporating home

practice and long-­‐term follow-­‐up also appears warranted.

Title: Key factors for overcoming psychological insulin resistance: an examination of patient perspectives through content analysis Citation: BMJ Open Diabetes Research and Care 2019;7:e000723. Author(s): Stuckey H. Abstract: Based on these themes, two actionable strategies are suggested for HCPs to help people with psychological insulin resistance: (1) demonstrate the injection process and discuss negative perceptions of insulin

as well as potential benefits; (2) offer autonomy in a person-­‐centred collaborative approach, but provide support and accessibility to address concerns. These findings help HCPs to better understand ways in which they can engage reluctant people with T2D with specific strategies.

Pharmacological management of diabetes Articles

Title: Clinical and economic outcomes among injection-­‐naïve patients with type 2 diabetes

initiating dulaglutide compared with basal insulin in a US real-­‐world setting: the DISPEL Study Citation: BMJ Open Diabetes Research and Care 2019;7:e000884. Author(s): Mody R. Abstract: In this real-­‐world study, patients with T2D initiating dulaglutide demonstrated greater HbA1c reduction

compared with those initiating basal insulin. Although total diabetes-­‐related costs were similar, the total diabetes-

­‐related costs per HbA1c reduction were lower for dulaglutide, highlighting the importance of evaluating effectiveness along with the economic impact of medications.

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Title: Efficacy of Dulaglutide as a First Injectable Option for Patients with Type 2 Diabetes: A Post-

­‐Hoc Pooled Analysis Citation: Diabetes Therapy 10 (6), 2321-­‐30. Author(s): Patel H

Abstract: The addition of a once-­‐weekly GLP-­‐1RA, dulaglutide, demonstrated clinically meaningful HbA1c reduction in patients with T2D on different background OH regimens, making it an effective first injectable option.

Title: Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial. Citation: Diabetes Care 2019;42(12):2262-­‐2271. Abstract: Oral semaglutide was superior to placebo in reducing HbA1c and body weight when added to insulin with

or without metformin in patients with type 2 diabetes. The safety profile was consistent with other glucagon-­‐like peptide 1 receptor agonists.

Title: Glycemic efficacy and safety of glucagon-­‐like peptide-­‐1 receptor agonist on top of sodium-­‐glucose co-­‐ transporter-­‐2 inhibitor treatment compared to sodium-­‐glucose co-­‐transporter-­‐2

inhibitor alone: A systematic review and meta-­‐analysis of randomized controlled trials Citation: Diabetes Research and Clinical Practice 158, 107927 Author(s): Patoulias D. Abstract: This meta-­‐analysis suggests that a GLP-­‐1RA/SGLT-­‐2i combination, if tolerated, exerts significant beneficial effects on glycemic control and body weight loss, however increasing the risk for any hypoglycemia and gastrointestinal adverse events.

Title: Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin. The PIONEER 2 Trial.

Citation: Diabetes Care 2019;42(12):2272-­‐2281. Author(s): Rodbard HW. Abstract: Oral semaglutide was superior to empagliflozin in reducing HbA1c but not body weight at 26 weeks in patients with type 2 diabetes uncontrolled on metformin. At week 52, HbA1c and body weight (trial product estimand) were significantly reduced versus empagliflozin. Oral semaglutide was well tolerated within the established safety profile of GLP-­‐1 receptor agonists.

Title: Orally Administered Semaglutide Versus GLP-­‐1 RAs in Patients with Type 2 Diabetes Previously Receiving 1-­‐2 Oral Antidiabetics: Systematic Review and Network Meta-­‐Analysis Citation: Diabetes Therapy 10 (6), 2183-­‐99. Author(s): Nuhoho S. Abstract: Orally administered semaglutide 14 mg QD as an add-­‐on to 1-­‐2 OADs is one of the most efficacious

GLP-­‐ 1 RAs for reducing HbA1c and body weight at 26 ± 4 weeks. Orally administered semaglutide 14 mg QD is

well tolerated, with a safety profile in line with the GLP-­‐1 RA class.

Title: Safety of Ipragliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Phase II/III/IV Clinical Trials Citation: Diabetes Therapy 10 (6), 2201-­‐17. Author(s): Kashiwagi A. Abstract: In randomised, placebo-­‐controlled trials of patients with T2DM, ipragliflozin was well tolerated, with a similar overall incidence of TEAEs to placebo. No new safety signals were observed.

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Title: SGLT2 inhibitors as adjunctive therapy for type 1 diabetes: balancing benefits and risks Citation: The Lancet Diabetes & Endocrinology 7(12), pp.949-­‐58. Author(s): Taylor S.I. Abstract: In this Personal View, we summarise data from eight clinical trials of canagliflozin, dapagliflozin, empagliflozin, and sotagliflozin in patients with type 1 diabetes.

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