Intensive glucose control and macrovascular outcomes in type 2 diabetes

Abstract

Aims/hypothesis Improved glucose control in type 2 diabetes is known to reduce the risk of microvascular events. There is, however, continuing uncertainty about its impact on macrovascular disease. The aim of these analyses was to generate more precise estimates of the effects of more-intensive, compared with less-intensive, glucose control on the risk of major cardiovascular events amongst patients with type 2 diabetes. Methods A prospectively planned group-level metaanalysis in which characteristics of trials to be included, outcomes of interest, analyses and subgroup definitions were all pre-specified. Results A total of 27,049 participants and 2,370 major vascular events contributed to the meta-analyses. Allocation to more-intensive, compared with less-intensive, glucose control reduced the risk of major cardiovascular events by 9% ( 2009 ) 52:2288 -2298 DOI 10.1007 /s00125-009-1470 treated participants had significantly more major hypoglycaemic events (HR 2.48,. Exploratory subgroup analyses suggested the possibility of a differential effect for major cardiovascular events in participants with and without macrovascular disease (HR 1.00, 95% CI 0.89-1.13, vs HR 0.84, 95% CI 0.74-0.94, respectively; interaction p=0.04). Conclusions/interpretation Targeting more-intensive glucose lowering modestly reduced major macrovascular events and increased major hypoglycaemia over 4.4 years in persons with type 2 diabetes. The analyses suggest that glucoselowering regimens should be tailored to the individual.

Relationship of glycaemic control and hypoglycaemic episodes to 4‐year cardiovascular outcomes in people with type 2 diabetes starting insulin

“…These results are broadly in line with the less‐certain effects seen in major randomized trials, and they support the conclusion that improved glycaemic control reduces CV events 6, 17, 18. Participants were newly started on insulin and generally achieved and maintained reasonable glycaemic control during follow‐up in the study, with median HbA1c of 9.3% (78 mmol/mol) at baseline, declining to 7.4% (57 mmol/mol) at the end of year 1 and 7.3% (56 mmol/mol) at the end of year 4.…”

“…The relationship between HbA1c reduction and CV events in the UKPDS was also suggestive, but uncertain at study end, but again significant at the end of the extension phase (MI, all‐cause mortality), and in study observational analysis 17, 19, 22. Accordingly, the meta‐analyses of these studies also found statistically significant reductions in MI and overall CV events 18, 23.…”

Intensified glucose lowering in type 2 diabetes: time for a reappraisal

“…When the studies are combined, there is consensus that non-fatal coronary episodes are reduced by intensive control, whereas stroke, cardiovascular mortality and total mortality are unaffected [20][21][22][23]. Differences between the Rx 2-3 years -16%…”

The management of type 2 diabetes with fixed‐ratio combination insulin degludec/liraglutide (IDegLira) versus basal‐bolus therapy (insulin glargine U100 plus insulin aspart): A short‐term cost‐effectiveness analysis in the UK setting

“…Type 2 diabetes mellitus accounts for approximately 90% of diabetes cases, and is primarily caused by insulin resistance, with progressive beta‐cell loss eventually leading to insulin deficiency 2, 3. Poor glycaemic control has been linked to an increased risk of diabetes‐related complications, including retinopathy, nephropathy, autonomic nervous system malfunction, diabetic foot (possibly requiring amputation) and increased risk of stroke and myocardial infarction 4, 5, 6, 7, 8, 9, 10, 11…”