In the Lancet Diabetes & Endocrinology, Hertzel Gerstein and colleagues report stroke outcomes from the researching cardiovascular events with a weekly incretin in diabetes (REWIND) trial, a cardiovascular outcomes study that investigated the effect of the glucagon-like peptide 1 (GLP-1) receptor agonist dulaglutide (1·5 mg subcutaneous weekly) compared with placebo in 9901 participants with type 2 diabetes and increased cardiovascular risk. During a median follow-up of 5·4 years, the primary outcome, a composite of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes, was reduced with dulaglutide compared with placebo (hazard ratio [HR] 0·88, 95% CI 0·79–0·99; p=0·026).

Glucagon-like peptide-1 (GLP-1) receptor agonists are commonly used as second-to-third line drugs in the treatment of type 2 diabetes. They include exenatide and lixisenatide, which are structurally similar to exendin-4, a peptide found in the saliva of the Gila monster lizard (exendin-based GLP-1 receptor agonists). In contrast, liraglutide, dulaglutide, albiglutide, and semaglutide are structurally analogous to the human GLP-1 molecule (human-analogue GLP-1 receptor agonists). Although potentially life-threatening allergies, such as anaphylactic reactions, have been documented with all GLP-1 receptor agonists,,  whether differences exist between exendin-based and human-analogue GLP-1 receptor agonists is unclear.

Mr A is a 89 year old patient with type 2 diabetes, congestive heart failure, end-stage kidney disease, and anaemia. His diabetes regimen consists of four insulin injections daily. He cannot take oral medications because of his kidney and heart diseases. His glucose concentrations range between 70 mg/dL and 150 mg/dL before breakfast, and between 80 mg/dL and 160 mg/dL before meals and at bedtime. His HbA 1C result—although not reliable because of his anaemia—is 7·1% (54 mmol/mol).

The purpose of this Review is to examine the associations between physical activity and skeletal health, with an emphasis on observational studies with fracture outcomes and randomised controlled trials (RCTs) of physical activity interventions in adults older than 40 years. In general, increased physical activity—primarily leisure time activity or moderate or vigorous physical activity—is associated with a 1–40% lower risk of hip and all fractures. The primary limitation of these studies relates to health status; healthy people are more likely to exercise and less likely to fracture. Although there is no sufficiently powered RCT of exercise with a fracture outcome, there is evidence that some types of exercise prevent falls and bone loss, and meta-analyses support the anti-fracture effectiveness of exercise. RCTs and meta-analyses suggest that programmes combining impact exercise with moderate or high-intensity progressive resistance exercise might maintain or improve bone mass and prevent fractures, and that functional strength and balance training prevents falls.

In The Lancet Diabetes & Endocrinology, Simon Griffin and colleagues report the results of a 10-year follow-up analysis of the Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen-Detected Diabetes in Primary Care (ADDITION-Europe), assessing outcomes 5 years post-intervention. The pragmatic, cluster-randomised, parallel-group trial was designed to examine effects of early intensive multifactorial treatment on cardiovascular outcomes in patients with newly diagnosed type 2 diabetes identified through screening. The primary endpoint was a composite of first cardiovascular event, including cardiovascular mortality, cardiovascular morbidity (non-fatal myocardial infarction and non-fatal stroke), revascularisation, and non-traumatic amputation. 343 general practices in Denmark, the Netherlands, and the UK were randomly assigned to routine diabetes care or intensive multifactorial treatment. Between April, 2001, and December, 2006, population-based stepwise screening programmes among people aged 40–69 years in these general practices identified 3057 patients with type 2 diabetes who agreed to participate in the trial. Less than 10% of patients had a history of myocardial infarction or stroke.

Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2019; 7: 845–54—In this Article, in figure 5B, the ptrend should be labelled “for UACR subgroup”. This correction has been made to the online version as of Oct 25, 2019.

Kelsall A, Newell-Price J. Cushing's disease—from Minnie G to key issues in the early 21st century. Lancet Diabetes Endocrinol 2019; 7: 959–64—In figure 2 of this TimeCapsule the 2015 entry reads “USP8 discovered”. It should have read “Mutations in USP8 linked to Cushing's disease”. This correction has been made as of Nov 19, 2019 and the printed version is correct.

Among the newest glucose-lowering agents for the treatment of type 2 diabetes, two classes raise much interest: glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Indeed, both showed a cardiovascular protection in dedicated outcome studies in patients with type 2 diabetes at high cardiovascular risk. ,  These findings had a major effect on the newer guidelines for the management of type 2 diabetes. In patients with atherosclerotic cardiovascular disease, guidelines now recommend, after failure of metformin monotherapy, the addition of a GLP-1 receptor agonist or an SGLT2 inhibitor that was shown to reduce the risk of major cardiovascular events. In the absence of heart failure or renal disease, two conditions in which SGLT2 inhibitors appear more protective, the clinician can choose between these two pharmacological options without specific guidance in the absence of comparative trials.

By contrast with the major developments in cardiovascular therapeutics, an entire generation has gone by with no new treatments to effectively stem the rising tide of kidney failure in people with diabetes. For those individuals unfortunate enough to have end-stage kidney disease, fewer than half will be alive after 5 years of maintenance haemodialysis. And for those whose kidney function is less impaired, every incremental reduction in estimated glomerular filtration rate (eGFR) or rise in albuminuria exponentially increases the risk of death or cardiovascular morbidity.

We read with interest the study by Zaharia and colleagues, who adopted the diabetes five-cluster algorithm proposed in 2018 by Ahlqvist and colleagues and characterised a cohort of patients with different degrees of whole-body and adipose-tissue insulin resistance. The authors reported distinct metabolic alterations and specific risk patterns for the development of diabetes-related comorbidities and complications after 5 years of follow-up. Here, we comment on two methodological aspects of this study.

We thank Shufang Liu and Wenquan Niu for their interest in our Article, which applied the clustering algorithm proposed by Ahlqvist and colleagues to patients with diabetes in the German Diabetes Study (GDS). We would like to respond to their comments on the methodological aspects of our study.

In the population-based cohort study by Buyun Liu and colleagues, maternal pre-pregnancy obesity was significantly associated with an increased risk of preterm birth on analysis of over 7 million mother–child pairs, and the magnitude of this association differed greatly by maternal age and race or ethnicity. This study provides important findings that enhance our knowledge of the management of maternal pre-pregnancy obesity, and these findings might subsequently lead to a plan for the development of prevention programmes for preterm birth. However, we would like to voice two concerns regarding the interpretation of the results.

Zinman B, Bhosekar V, Busch R, et al. Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes (SUSTAIN 9): a randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2019; 7: 356–67—In table 3 of this Article, data on event adjudication committee-confirmed cardiovascular events were added for both groups. This change does not affect the written interpretation. The legend of table 3 was updated to add the following footnote, as related to this new row: “§There was one duplicate event of transient ischaemic attack in one patient.”. These corrections have been made to the online version as of Oct 15, 2019.

Fleseriu M, Pivonello R, Elenkova A, et al. Efficacy and safety of levoketoconazole in the treatment of endogenous Cushing's syndrome (SONICS): a phase 3, multicentre, open-label, single-arm trial. Lancet Diabetes Endocrinol 2019; 7: 855–65—In this Article, in the Study design and patients section of the Methods, 230 h should be 2300 h. In the Results section, 95% CI −10·7 to −0·79 should be nmol/L. Changes have been made for data alignment, figure axes, and addition to the key in figure 2. These corrections have been made to the online version as of Oct 15, 2019, and the printed version is correct.