Lancet Diabetes Research Articles

GLP-1 receptor agonists in type 1 diabetes: a MAG1C bullet?

Although the mainstay of glycaemic control in type 1 diabetes has been the replacement of insulin to address the secretory deficiency caused by destruction of β cells, supplementary glucose-lowering treatments such as metformin, amylin analogues, SGLT2 inhibitors, and GLP-1 receptor agonists have been tested in clinical trials hoping for improved efficacy and safety. 1 Frandsen CS Dejgaard TF Madsbad S Non-insulin drugs to treat hyperglycaemia in type 1 diabetes mellitus. Lancet Diabetes Endocrinol. 2016; 4: 766-780 Summary Full Text Full Text PDF PubMed Scopus (62) Google Scholar Efficacy and safety of meal-time administration of short-acting exenatide for glycaemic control in type 1 diabetes (MAG1C): a randomised, double-blind, placebo-controlled trialShort-acting exenatide does not seem to have a future as a standard add-on treatment to insulin therapy in type 1 diabetes. Full-Text PDF

LDL cholesterol: lower, faster, younger?

Findings from recent clinical trials of LDL cholesterol lowering suggest continued benefits at lower concentrations than those previously considered acceptable. In The Lancet Diabetes & Endocrinology, Nelson Wang and colleagues emphasise this concept in their large meta-analysis 1 Wang N Fulcher J Abeysuriya N et al. Intensive LDL cholesterol-lowering treatment beyond current recommendations for the prevention of major vascular events: a systematic review and meta-analysis of randomised trials including 327 037 participants. Lancet Diabetes Endocrinol. 2020; 8: 36-49 Summary Full Text Full Text PDF PubMed Scopus (62) Google Scholar that incorporates results of 52 randomised controlled trials of cholesterol-lowering drugs with a primary composite cardiovascular endpoint. Across three mechanistically distinct drug classes—statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors—there was a direct linear association between pharmacological LDL cholesterol lowering and relative risk reduction in cardiovascular events. A 1 mmol/L reduction in LDL cholesterol corresponded to a relative risk reduction of 19%, irrespective of baseline LDL cholesterol concentration or drug class used. Although the analysis used average LDL cholesterol concentrations in the treatment versus control groups, rather than individual participant level data, it still provides compelling evidence for the cardiovascular benefit of LDL cholesterol reduction, with no apparent lower threshold for additional benefit. Intensive LDL cholesterol-lowering treatment beyond current recommendations for the prevention of major vascular events: a systematic review and meta-analysis of randomised trials including 327 037 participantsFor each 1 mmol/L LDL cholesterol lowering, the risk reduction of major vascular events is independent of the starting LDL cholesterol or the presence of diabetes or chronic kidney disease. Patients at lower cardiovascular risk and younger age might have a similar relative reduction in risk with LDL-cholesterol lowering therapies and future studies should investigate the potential benefits of earlier intervention. Full-Text PDF

Class effect: dapagliflozin reduces cardiovascular and kidney events

The sodium-dependent glucose co-transporter (SGLT-2) inhibitors are the newest class of oral agents in the armory of the physician to combat type 2 diabetes mellitus (T2DM). The significant reduction in cardiovascular outcomes with all 3 SGLT-2 inhibitors is now well documented,1–3 as is the reduction in chronic kidney disease (CKD) outcomes with canagliflozin.4 The effect of another SGLT-2 inhibitor, dapagliflozin, on long-term CKD outcomes is the subject of a secondary analysis of the Dapagliflozin Effect on Cardiovascular Events–Thrombolysis In Myocardial Infarction 58 (DECLARE-TIMI 58) trial, recently published in Lancet Diabetes and Endocrinology.

A135 Postoperative remission of type 2 diabetes according to data driven cluster patient classification prior to bariatric surgery.

Baseline patient characteristics associated with remission of type 2 diabetes (T2D) after bariatric surgery (BS) are debated. A refined data driven cluster classification of diabetes has been recently proposed to identify individuals with increased risk of complication and help individualize treatment regimens (Ahlqvist Lancet Diabetes Endocrinol 2018). The impact of this new classification on the outcome of BS is unknown. Objectives: To analyze the relation between data driven cluster classification of T2D patients prior to BS and diabetes related outcomes one year after BS.

In high-risk type 1 diabetes, insulin pumps with suspend-before-low technology reduced hypoglycemic events.

Source Citation Bosi E, Choudhary P, de Valk HW, et al; SMILE Study Group. Efficacy and safety of suspend-before-low insulin pump technology in hypoglycaemia-prone adults with type 1 diabetes (SMILE): an open-label randomised controlled trial. Lancet Diabetes Endocrinol. 2019;7:462-72. 31047902

Repercussions of diabetes mellitus on the oral cavity

AbstractOral health is a cardinal element of nutritional as well as systemic well-being and plays a substantial part in sustaining optimum general health condition. Various factors influence oral health including metabolic diseases such as endocrine (diabetes mellitus [DM]), hematological, gastrointestinal, cutaneous, and neurological diseases. The intent of this review is to accentuate the correlation between DM and oral disorders, like those upsetting oral mucosa and supporting tissues. A review of literature was performed using relevant key words (“Oral Manifestations of Diabetes” OR “Oral Complications of Diabetes” OR “Oral Impacts of Diabetes” OR “Oral Repercussions of Diabetes“) in prominent journals pertaining to Endocrinology and Dentistry (Journal of Periodontology, Periodontology 2000, British Dental Journal, The Lancet Diabetes and Endocrinology, PloS ONE, and Nature Reviews Genetics). The most frequently witnessed diabetic manifestations in oral cavity include gingivitis and periodontitis leading to premature tooth loss, salivary dysfunctions, dental caries, delayed wound healing, bacterial and fungal infections, lichen planus, taste impairment, tongue abnormalities, neurosensory oral disorders, halitosis, and dry socket. In the end, I have comprehensively described the role of antidiabetic drugs in the management of DM and eventually leading to prevention of its oral complications. In this review, etiopathophysiology of each oral complication has been prudently analyzed to contemplate the establishment of a possible preventive and treatment approach.

The Proposed 5 Subgroups of Diabetes Have Less Clinical Utility Than Models Using Simple Clinical Features: An Evaluation in Randomised Trial Data

Background: Recent research using data-driven cluster analysis has proposed five subgroups of diabetes with different diabetes progression and complication risk. We aimed to compare the clinical utility of this subgroup-based approach with an alternative strategy using specific outcome models that use routine clinical features. Methods: We identified clusters in the ADOPT (n=4,351) trial cohort using the cluster analysis reported by Ahlqvist and colleagues (Lancet Diabetes Endocrinology 2018;6:361-69). Differences between clusters in glycaemic and renal progression were evaluated, and contrasted with stratification using routine measures (age at diagnosis and baseline renal function). We tested the performance of a strategy of selecting glucose lowering therapy using clusters with one using simple clinical features (sex, BMI, age at diagnosis, baseline HbA1c) in an independent trial cohort (RECORD (n=4,447)). Findings: Clusters identified in trial data were similar to those described in the original study. Clusters showed differences in glycaemic progression, but a model with age at diagnosis alone had similar predictive ability. We found differences in CKD incidence between clusters however baseline eGFR was a better predictor of time to CKD. Clusters differed in glycaemic response, with a particular benefit for cluster 3 (insulin-resistant) with thiazolidinediones and cluster 5 (older) with sulfonylureas. However simple clinical features outperformed clusters to select therapy for individual patients. Interpretation: Precision medicine in type 2 diabetes is likely to have most clinical utility if based on an approach of using specific continuous clinical measures to predict specific outcomes, rather than stratifying patients into subgroups. Funding Statement: This work was supported by the Medical Research Council (UK) (MR/N00633X/1). Data for both ADOPT and RECORD trials were accessed through the Clinical Trial Data Transparency Portal under approval from GSK (Proposal 930). ATH is a NIHR Senior Investigator and a Wellcome Trust Senior Investigator (098395/Z/12/Z). AGJ is supported by an NIHR Clinician Scientist award (CS-2015-15- 018). JMD, ATH and BMS are supported by the NIHR Exeter Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the MRC, the NIHR or the Wellcome Trust Declaration of Interests: WEH declares a grant from IQVIA. All other authors declare no competing interests. Ethics Approval Statement: Individual-level participant data from the ADOPT and RECORD trials were accessed through the Clinical Trial Data Transparency Portal, with study approval from GlaxoSmithKline (Proposal 930). Both trials were conducted according to Good Clinical (Research) Practice guidelines and the Declaration of Helsinki (1996).

In type 2 diabetes, a primary care–led weight management program increased weight loss and diabetes remission at 2 years

Source Citation Lean ME, Leslie WS, Barnes AC, et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol. 2019;7:344-55. 30852132

GLP-1 receptor agonists and cardiovascular outcomes: an updated synthesis

In The Lancet Diabetes & Endocrinology, Søren Kristensen and colleagues present a new, up-to-date systematic review and meta-analysis 1 Kristensen SL Rørth R Jhund PS et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; (published online Aug 14.)http://dx.doi.org/10.1016/S2213-8587(19)30249-9 Summary Full Text Full Text PDF PubMed Scopus (323) Google Scholar of cardiovascular outcome trials evaluating glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes—a timely update after the recent reporting of the primary results from the REWIND trial of dulaglutide 2 Gerstein HC Colhoun HM Dagenais GR et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019; 394: 121-130 Summary Full Text Full Text PDF PubMed Scopus (674) Google Scholar , 3 Gerstein HC Colhoun HM Dagenais GR et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet. 2019; 394: 131-138 Summary Full Text Full Text PDF PubMed Scopus (164) Google Scholar and the PIONEER 6 trial of oral semaglutide. 4 Husain M Birkenfeld AL Donsmark M et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019; (published online June 11.)DOI:10.1056/NEJMoa1901118 Crossref PubMed Scopus (391) Google Scholar Incorporating these new trials means that the new meta-analysis includes data from seven trials with a total of 56 004 patients and, of those with available data for the primary outcome of major adverse cardiovascular events (MACE), includes a minority of 12 983 patients who did not have established cardiovascular disease but rather had multiple cardiovascular risk factors (thus being considered primary prevention patients) and 10 773 patients with an estimated glomerular filtration rate of less than 60 mL/min per 1·73 m2. The findings from the meta-analysis thereby contribute useful evidence concerning the cardiovascular safety and efficacy of GLP-1 receptor agonists across a range of patient populations. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trialsTreatment with GLP-1 receptor agonists has beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes. Full-Text PDF

Sophia Zoungas: clinician, researcher, and full-time mum

Endocrinologist Sophia Zoungas often uses an unusual patient case study when presenting at conferences—her father, John Zoungas. “Dad has had a heart attack, he takes statins, has diabetes, and is on blood pressure medications”, she tells The Lancet Diabetes & Endocrinology. “Now most delegates know when I refer to the mysterious patient case study JZ, I'm talking about him!”

SUN-396 Subclinical Cushing's Syndrome: Should We Treat?

Background: Subclinical (mild) Cushing’s syndrome (SCS) is a common finding in incidental adrenal masses. Recent studies have shown there is increased morbidity and mortality with SCS. We present two cases that illustrate the importance of aggressive treatment of SCS. Clinical Case: A 66-yr-old female with multiple sclerosis and HTN presented to the ER with a 3-week history of hypertensive paroxysms >200/110. HTN previously has been well controlled with metoprolol and olmesartan. Evaluation for pheochromocytoma was negative. ACTH was <5 pg/mL, AM cortisol 14.6 mcg/dL, 24-hr-urine cortisol 108.4 mcg/d (RR <50), and 1 mg dexamethasone suppression test showed plasma cortisol 1.9 mcg/dL (RR <1.8). Patient was maintained on Toprol XL, amlodipine, amiloride, clonidine patch, and clonidine tablets. She continued to experience hypertensive paroxysms in addition to fatigue, hypersomnolence, proximal muscle weakness and developed pre-diabetes (HbA1c 6.1%). CT abdomen showed left adrenal thickening; 8 AM cortisol 23.4 mcg/dL (RR 6-18.4) and 11 pm salivary cortisol 0.145 mcg/d (RR <0.112). Mifepristone 300 mg QD and spironolactone 50 mg QD were initiated. Within 2 months, patient had resolution of hypertensive swings, was off clonidine, had a 25-50% improvement in muscle strength, and HbA1c 5.9%. Clinical Case: A 67-yr-old male with coronary disease and HTN presented with a BP of 240/130. Work up revealed left adrenal mass of 1.5 x 2.9 x 1.4cm. Endocrine work up was negative except for 24-hr-urine cortisol 100 mcg/day (RR <50). Patient maintained on 4 antihypertensive medications. He continued to have borderline HTN, weight gain, and developed pre-diabetes (FBG 116). CT scan at 6 months showed decreased L adrenal adenoma of 1.7 cm. Two years after initial presentation, 1 mg dexamethasone test showed AM cortisol 1.9 mcg/dL (RR <1.8), 11 pm salivary cortisol x2 negative, and repeat 24-hour urine cortisol 58 mcg/d (RR <50). Physical exam was negative for Cushingoid features. Patient was pretreated with mifepristone and underwent L adrenalectomy. Pathology was consistent with nodular adrenal hyperplasia with positive ACTH staining. Six months following surgery, improved blood pressure and glycemic control were noted allowing medication dose reduction. Discussion: It is important to recognize that patients with adrenal SCS are at increased risk for metabolic disease, cardiovascular incidents, and mortality. Patients should be monitored closely, and treatment can result in improved metabolic parameters and quality of life. Reference: Di Dalmazi, G., et al. (2014). Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cusing’s syndrome: 15-year retrospective study. The Lancet Diabetes & Endocrinology, Vol 2, Issue 5, 396-405.

SAT-433 Long-Acting Pasireotide Provides Clinical Benefit to Patients with Uncontrolled Acromegaly over Continued Treatment with First‑Generation Somatostatin Analogues (SSAs): Results from Phase 3b, Open-Label Study

Background: In a 24-week, Phase 3 study (PAOLA), long-acting pasireotide demonstrated superior efficacy (GH <2.5 µg/L and IGF-1 <ULN) over continued treatment with long-acting octreotide/lanreotide in pts with uncontrolled acromegaly (Gadelha MR, et al. Lancet Diabetes Endocrinol. 2014;2:875-884). An earlier (3 months) switch to long-acting pasireotide and the current criteria for biochemical control, i.e. GH <1 μg/L and IGF-1 <ULN, are considered in the present phase 3b study. This study (clinicaltrials.gov: NCT02354508) evaluated the efficacy (GH <1 μg/L and IGF-1 <ULN) and safety of long‑acting pasireotide in pts with uncontrolled acromegaly despite ≥3 months of treatment with maximal approved doses of first-generation SSAs. Methods: Adults with uncontrolled acromegaly (mean GH [mGH] ≥1 µg/L and IGF-1 >1.3xULN) despite ≥3 months of treatment with maximal approved doses of long-acting octreotide/lanreotide received open-label long-acting pasireotide 40 mg/28 days. Pasireotide dose could be up titrated to 60 mg/28 days after week 12 if the biochemical control was not achieved or down titrated to 20 mg/28 days or 10 mg/28 days for tolerability. Primary endpoint: proportion of pts with mGH <1 μg/L and IGF-1 <ULN at week 36 overall and by screening mGH (1.0-2.5 μg/L and >2.5 μg/L). Results: 123 pts received long-acting pasireotide: median age, 43.0 years (range, 22-76); female, 50.4%; baseline median (range) mGH, 5.4 µg/L (1.2-195.5) and IGF-1, 2.3xULN (1.4-7.9); prediabetic/diabetic at baseline, n=112 (91.1%). The median duration of exposure to pasireotide was 36.0 weeks (median dose intensity, 53.3 mg/month). Overall, 18 pts (14.6% [95%CI, 8.9-22.1]) achieved biochemical control at week 36 (primary endpoint); 12 (42.9% [95%CI, 24.5-62.8]) and 6 pts (6.4% [95%CI, 2.4-13.4]) by screening mGH levels of 1.0 to 2.5 µg/L (n=28) and >2.5 µg/L (n=94), respectively. At week 36, 23 (18.7%), 16 (57.1%) and 7 pts (7.4%) had GH <1 µg/L; and 38 (30.9%), 14 (50.0%) and 24 pts (25.5%) had IGF-1 <ULN overall and by screening mGH levels of 1.0 to 2.5 µg/L and >2.5 µg/L, respectively. The median percentage decreases in mGH and standardized IGF-1 from baseline to week 36 were 56.8% and 42.8%. The most common AEs (>15%) regardless of study drug relationship were hyperglycemia (43.1%), diabetes mellitus (22.0%), and diarrhea (15.4%). Hyperglycemia-related AEs suspected to be drug related occurred in 81 pts (66%) overall and 4 of 11 pts (36.4%) who were nondiabetic at baseline. A total of 10 pts (8.1%) discontinued treatment either because of AEs (n=4; 3.3%) or unsatisfactory therapeutic effect (n=3; 2.4%), or consent withdrawal (n=3; 2.4%). Conclusions: In pts with uncontrolled acromegaly, switching to long-acting pasireotide after ≥3 months of treatment with first-generation SSAs provided biochemical control (mGH <1.0 μg/L and IGF-1 <ULN) in 15% of all pts and 43% of pts with lower screening mGH (1.0-2.5 µg/L).

Impact of Family History of Diabetes on Diabetes Control and Complications

Type 2 diabetes (T2D) is a growing health concern, associated with increasing morbidity and mortality. It is projected to be one of the few rising causes of mortality, behind human immunodeficiency virus/AIDS and above motor vehicle accidents ( 1. Mathers C.D. Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006; 3: e442 Crossref PubMed Scopus (7571) Google Scholar ). The prevalence of T2D is projected to increase by 23 to 110%, depending on the region, with the biggest increase anticipated in Africa, South America, and South Asia ( 2. Zimmet P.Z. Magliano D.J. Herman W.H. Shaw J.E. Diabetes: a 21st century challenge. Lancet Diabetes Endocrinol. 2014; 2: 56-64 Abstract Full Text Full Text PDF PubMed Scopus (560) Google Scholar ). Understanding the causes of the increased risk for developing diabetes may help target our global preventive efforts more effectively. Identifying individuals at risk for developing diabetes at a younger age and at risk for developing more severe complications from diabetes may help target therapy and interventions.

Obesity in Adolescents and Youth: The Case for and against Bariatric Surgery

Obesity in Adolescents and Youth: The Case for and against Bariatric Surgery

PCV33 - THE RATE OF CARDIOVASCULAR EVENTS IN DIABETIC PATIENTS IN COLOMBIA

To estimate the rate at which acute coronary events present themselves in diabetic patients from a Colombian insurance company through big data analysis. Based on cluster technics and association rules applied over databases of service consumption from a health insurance company with distribution across the country, diabetic patients from a sole year and those who presented acute coronary events, for at least a year or until death, were singled out for the study. Acute coronary events were defined via diagnosis and validated through registered consumption. Patients were analyzed globally and set apart by stage of treatment: monotherapy, oral combination therapy or insulinized. From 131’604.958 records from approximately 2’300.000 different users, 7,639 patients were diagnosed with type 2 diabetes mellitus for 2015 at a mean age of 56.4, from whom 37% were identified with at least one separate chronic pathology. From the specified population, 85 presented cardiovascular events; equal to a rate of 1.1%. When analyzing specifically those patients under insulinization the rate corresponded to 1.35%. The risk ratio of presenting a coronary event for the diabetic population which did not present any other pathologies was 0.39. The event rate obtained is similar to that of a study performed in international populations such as the one published in Lancet Diabetes Endocrinology in 2014. When analyzing the variations by type of population, it is proven that acute coronary events present a major risk factor in those patients with other chronic pathologies and that those patients who are insulinized have a 2.4% higher rate of presenting cardiovascular events.

Research digest: CV trials in diabetes—looking ahead

In the half decade since the launch of The Lancet Diabetes & Endocrinology, we have seen some exciting developments in diabetes research. Not least among these are the results from the plethora of industry-sponsored cardiovascular (CV) outcome trials that resulted from the US Food and Drug Administration (FDA) requirement that the safety and efficacy of any new glucose-lowering drug be based on hard clinical outcomes rather than its effects on glucose or HbA1c, with findings that have transformed treatment options in type 2 diabetes. But looking to the future, there are important challenges to overcome in terms of trial design, including tremendous costs and the need for new trials to answer the most clinically relevant questions for the greatest number of patients.

A renaissance in diabetic foot care: new evidence-based treatments

Unhealed diabetic foot ulcers can result in up to 84% of lower extremity amputations. 1 Pecoraro R Reiber G Burgess E Pathways to diabetic limb amputation: basis for prevention. Diabetes Care. 1990; 13: 513-521 Crossref PubMed Scopus (1230) Google Scholar , 2 Larsson J Apelqvist J Agardh CD Stenström A Decreasing incidence of major amputation in diabetic patients: a consequence of a multidisciplinary foot care team approach?. Diabet Med. 1995; 12: 770-776 Crossref PubMed Scopus (315) Google Scholar It is thus important that ulcers are healed quickly. However, there has been a scarcity of evidence-based topical therapy to accelerate the healing of diabetic foot ulcers and this drought has led to a call for well-designed clinical trials. 3 Jeffcoate WJ Bus SA Game FL Hinchliffe RJ Price PE Schaper NC International Working Group on the Diabetic Foot and the European Wound Management AssociationReporting standards of studies and papers on the prevention and management of foot ulcers in diabetes: required details and markers of good quality. Lancet Diabetes Endocrinol. 2016; 4: 781-788 Summary Full Text Full Text PDF PubMed Scopus (124) Google Scholar Over the past year, there has been a renaissance in diabetic foot care and three relatively robust trials on foot ulcers have been published. The first (the Explorer study 4 Edmonds M Lazaro-Martinez JL Alfayate-Garcia JM et al. Sucrose octasulfatedressing versus control dressing in patients with neuroischaemic diabetic foot ulcers (Explorer): an international, multicentre, double-blind, randomised, controlled trial. Lancet Diabetes Endocrinol. 2018; 6: 186-196 Summary Full Text Full Text PDF PubMed Scopus (117) Google Scholar ) reported the benefit of sucrose octasulphate dressing and the second (the ProNOx1 study 5 Edmonds ME Bodansky HJ Boulton AJ et al. Multicenter, randomized controlled, observer-blinded study of a nitric oxide generating treatment in foot ulcers of patients with diabetes – ProNOx1 study. Wound Repair Regen. 2018; (published online April 4.)DOI:10.1111/wrr.12630 Crossref Scopus (25) Google Scholar ) reported the positive outcome of a nitric oxide generating device. The third study (LeucoPatch 6 Game F Jeffcoate W Tarnow L et al. LeucoPatch system for the management of hard-to-heal diabetic foot ulcers in the UK, Denmark, and Sweden: an observer-blinded, randomised controlled trial. Lancet Diabetes Endocrinol. 2018; (published online September 7.)http://dx.doi.org/10.1016/S2213-8587(18)30240-7 Summary Full Text Full Text PDF PubMed Scopus (66) Google Scholar ) reported the benefit of a multi-layered patch comprising autologous leucocytes, platelets, and fibrin, which releases cytokines and growth factors involved in tissue repair, 7 Game FL Apelqvist J Attinger C et al. Effectiveness of interventions to enhance healing of chronic ulcers of the foot in diabetes: a systematic review. Diabetes Metab Res Rev. 2016; 32: 154-168 Crossref PubMed Scopus (121) Google Scholar in a multinational, observer-blinded, randomised, controlled trial now published in The Lancet Diabetes & Endocrinology by Frances Game and colleagues. 6 Game F Jeffcoate W Tarnow L et al. LeucoPatch system for the management of hard-to-heal diabetic foot ulcers in the UK, Denmark, and Sweden: an observer-blinded, randomised controlled trial. Lancet Diabetes Endocrinol. 2018; (published online September 7.)http://dx.doi.org/10.1016/S2213-8587(18)30240-7 Summary Full Text Full Text PDF PubMed Scopus (66) Google Scholar The trial recruited people with hard-to-heal ulcers, which were defined as ulcers that had less than a 50% reduction of area in response to standard care during a 4-week run-in period. 34% of these ulcers healed within 20 weeks in the intervention group (together with standard care) compared with 22% in patients undergoing standard care alone (odds ratio 1·58, 96% CI 1·04–2·40; p=0·0235). LeucoPatch system for the management of hard-to-heal diabetic foot ulcers in the UK, Denmark, and Sweden: an observer-masked, randomised controlled trialThe use of LeucoPatch is associated with significant enhancement of healing of hard-to-heal foot ulcers in people with diabetes. Full-Text PDF

Diabetes in sub-Saharan Africa: from clinical care to health policy

The Lancet Diabetes and Endocrinology Commission provides a comprehensive, evidence-based review of diabetes in sub-Saharan Africa, one of the most important emerging diseases and markers of the global epidemic of non-communicable diseases. The authors provide a detailed analysis of the significant knowledge gaps in the global epidemiology and burden of diabetes and its complications in sub-Saharan Africa and emphasize the need to develop local systems to ascertain population representative data. The commission delineates the current health system’s barriers adequate diabetes care delivery in the region, concluding that sub-Saharan Africa remains ill equipped in terms of diagnostic and monitoring tools, adequately trained health care professionals, access to essential therapeutics, and availability of guidelines and disease registries. They add an estimate of the economic burden of diabetes, including direct cost to the individual and indirect cost to countries, including the expected tripling in cost until 2030 and the anticipated inability of health systems in the region to assimilate this financial burden.

Long-Term Efficacy and Safety of Dapagliflozin in Patients with Inadequately Controlled Type 1 Diabetes—The DEPICT-1 Study

In the short term (24-week) period of the Phase 3 study DEPICT-1, treatment with the SGLT2 inhibitor dapagliflozin (DAPA) as adjunct to adjustable insulin (INS) improved glycemic control and was well-tolerated in patients with inadequately controlled T1D (HbA1c 7.5-10.5%) (Lancet Diabetes Endocrinol. 2017;5:864-76). Here we describe the 28-week extension of DEPICT-1, assessing the 52-week efficacy and safety of DAPA in patients who completed the 24-week period. 747 patients in the DAPA 5 mg (n=250), 10 mg (n=270), or placebo (PBO; n=227) plus INS groups entered the long-term period (90% of the randomized patients); 85% completed the study. Reductions in HbA1c and body weight were maintained in the DAPA groups vs. PBO over 52 weeks (Table). The moderate decrease in HbA1c with DAPA was accompanied by a more substantial dose-dependent reduction in body weight. Total events of adjudicated definite DKA increased in the long-term period, with more in the DAPA groups vs. PBO at Week 52. Most were mild or moderate, with the primary cause related to missed insulin doses or pump failure. Adverse events (AEs), serious AEs, and hypoglycemic events were balanced between groups (Table). In conclusion, DAPA plus INS provided a sustained reduction in HbA1c and body weight, and was well-tolerated, but increased events of DKA over 52 weeks in patients with inadequately controlled T1D.Efficacy outcomes at Week 52DAPA 5 mg + INS n=259*DAPA 10 mg + INS n=259*Placebo + INS n=260*A1c, % Week 52 adjusted mean change from baseline (SE) Difference vs PBO (95% CI). -0.27 (0.06) -0.33 (-0.49, -0.17). -0.31 (0.06) -0.36 (-0.53, -0.20). 0.06 (0.06) -Total body weight Week 52 adjusted mean percent change from baseline (SE) Difference vs PBO (95% CI). -2.80 (0.32) -2.95 (-3.83, -2.06). -4.39 (0.31) -4.54 (-5.40, -3.66). 0.15 (0.33) -Safety outcomes at Week 52, n (%)n=277†n=296†n=260†≥1 AE ≥1 SAE ≥1 related SAE ≥1 event of any hypoglycaemia ≥1 event of severe hypoglycaemia Events adjudicated as definite DKA ...Mild ...Moderate ...Severe215 (77.6) 37 (13.4) 8 (2.9) 227 (81.9) 29 (10.5) 12 (4.3) ...5 (1.8) ...3 (1.1) ...4 (1.4)236 (79.7) 40 (13.5) 13 (4.4) 241 (81.4) 25 (8.4) 10 (3.4) ...2 (0.7) ...6 (2.0) ...2 (0.7)189 (72.7) 30 (11.5) 2 (0.8) 212 (81.5) 30 (11.5) 5 (1.9) ...3 (1.2) ...1 (0.4) ...1 (0.4)AE, adverse event; CI, confidence interval; DAPA, dapagliflozin; PBO, placebo; INS, insulin; SAE, serious adverse event; SE, standard error. *n is the number of patients who received 52 weeks of treatment in the full analysis set (excludes the first 55 patients allocated to only DAPA groups due to an interactive voice response system randomization system error). †n is the number of patients who initiated the 24-week period in the safety analysis set (includes the first 55 patients incorrectly randomized to only DAPA groups). ‡Includes events monitored in both 24-week short-term period and 28-week extension. Disclosure P. Dandona: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. C. Mathieu: Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Sanofi. Research Support; Self; Merck Sharp &amp; Dohme Corp.. Speaker's Bureau; Self; Merck Sharp &amp; Dohme Corp.. Advisory Panel; Self; Merck Sharp &amp; Dohme Corp.. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Novartis AG. Speaker's Bureau; Self; Novartis AG. Advisory Panel; Self; Novartis AG, Bristol-Myers Squibb Company. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca, Pfizer Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Hanmi Pharmaceutical. Research Support; Self; Roche Diagnostics Corporation. Advisory Panel; Self; Roche Diagnostics Corporation. Research Support; Self; Medtronic. Advisory Panel; Self; Medtronic, MannKind Corporation. Research Support; Self; Intrexon. Advisory Panel; Self; Intrexon, Dianax, UCB, Inc.. Research Support; Self; Abbott. M. Phillip: Other Relationship; Self; Sanofi, Medtronic MiniMed, Inc., Novo Nordisk A/S. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Merck &amp; Co., Inc., Bristol-Myers Squibb Company, Kamada, Lexicon Pharmaceuticals, Inc.. Other Relationship; Self; DreaMed Diabetes, Ltd.. Speaker's Bureau; Self; Abbott. L. Hansen: Employee; Self; MedImmune. D. Tschoepe: Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; Amgen Inc.. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Servier. Speaker's Bureau; Self; Servier, Sanofi, Novartis Pharmaceuticals Corporation. Research Support; Self; AstraZeneca, Bayer AG, Eli Lilly and Company, Novo Nordisk A/S, Novartis Pharmaceuticals Corporation, Sanofi. F.A. Thoren: Employee; Self; AstraZeneca. J. Xu: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca.

Precision diabetes treatment comes a step closer

The recently published Lancet Diabetes and Endocrinology paper that identifies five subtypes of adult‐onset diabetes associated with differing risk of complications has sparked new debate on the classification of diabetes and may help bring precision medicine a step closer.