Intensive Glycemic Control in the ACCORD and ADVANCE Trials

Dluhy, Robert G.; McMahon, Graham T.

doi:10.1056/nejme0804182

Cited by 350 publications

(205 citation statements)

References 14 publications

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“…Both the United Kingdom Prospective Diabetes Study (UKPDS) in type 2 diabetes and the Diabetes Control and Complications Trial (DCCT) in type 1 diabetes have shown that an extended period of observation is required to establish whether an apparently favorable change in biomarkers, such as those observed herein, translates into favorable clinical vascular outcomes (3,30,31). In patients with type 2 diabetes with longer duration and at higher vascular risk than in ADOPT, rosiglitazone does not appear to provide specific cardiovascular protection (32)(33)(34). Nevertheless, it must be realized that early and late phases of a disease may respond quite differently to similar therapeutic agents and treatment strategies, as highlighted recently by trials of intensive glycemic control in type 2 diabetes (3,32-34).…”

Section: Discussionmentioning

confidence: 99%

Renal Function in Type 2 Diabetes with Rosiglitazone, Metformin, and Glyburide Monotherapy

Lachin

Viberti

Zinman

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives In ADOPT (A Diabetes Outcomes Prevention Trial), initial monotherapy with rosiglitazone provided more durable glycemic control than metformin or glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine differences in albumin excretion, renal function (estimated GFR), and BP over 5 years between treatment groups.Design, setting, participants, & measurements A total of 4351 recently diagnosed, drug-naïve patients with type 2 diabetes were treated and followed for up to 5 years with rosiglitazone, metformin, or glyburide and were examined with periodic assessments of albumin/creatinine ratio (ACR), modification of diet in renal disease (MDRD)-estimated GFR, and BP. ResultsThe ACR rose slowly with metformin. It fell with rosiglitazone and less so with glyburide over the first 2 years, and then rose slowly over time. Estimated GFR (eGFR) with all therapies rose into the high normal range over the first 3 to 4 years, more so with rosiglitazone, and then declined, more so with glyburide. Systolic BP was stable over time, values with rosiglitazone being lower, and diastolic BP declined over time, more so with rosiglitazone than with metformin or glyburide. There was no difference among groups in the incidence of emergent albuminuria (ACR Ն30 mg/g), hypertension, or impaired eGFR (Ͻ60 ml/min per 1.73 m 2 ).Conclusions Over a 5-year period, initial monotherapy with rosiglitazone retards the rise of ACR compared with metformin, preserves eGFR compared with glyburide, and lowers BP relative to both comparators.

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Section: Discussionmentioning

confidence: 99%

Renal Function in Type 2 Diabetes with Rosiglitazone, Metformin, and Glyburide Monotherapy

Lachin

Viberti

Zinman

et al. 2011

Clinical Journal of the American Society of Nephrology

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“…However, when the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study was published, showing an increased mortality among patients randomised to receive intensive glycaemic control, a less stringent HbA 1c goal was suggested for patients with a history of severe hypoglycaemia, a limited life expectancy or advanced diabetic complications [9]. The importance of hypoglycaemia has frequently been discussed as a plausible factor or mediator of this increased mortality, although no study has been able to show causality [10][11][12]. Hypoglycaemia alters several risk factors for mortality, including vasoconstriction and cytokine responses, and increases the likelihood of lethal arrhythmias [13][14][15][16][17].…”

mentioning

confidence: 99%

The impact of metabolic control and QTc prolongation on all-cause mortality in patients with type 2 diabetes and foot ulcers

Fagher

Löndahl

2013

Diabetologia

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Aims/hypothesis The increased all-cause mortality in patients with chronic diabetic foot ulcers cannot fully be explained by traditional cardiovascular risk factors. The significance of heart-rate-corrected QT (QTc) prolongation, a finding often seen in these patients, is unknown. Recently, the importance of metabolic control and hypoglycaemia has been discussed. The aim of this study was to evaluate the impact of different HbA 1c levels and QTc prolongation on all-cause mortality in the high-risk population of patients with type 2 diabetes mellitus and foot ulcers. Methods All patients with type 2 diabetes, younger than 80 years, visiting our diabetes foot unit, with a foot ulcer duration >4 weeks, were screened for participation. Patients on dialysis were excluded. Patients were grouped according to HbA 1c level and QTc time ≤ or >440 ms. Results Patients (n=214, median age 69.1 years) were grouped according to HbA 1c level (HbA 1c <7.5% [<58 mmol/mol] n=81, 7.5-8.9% [58-74 mmol/mol] n=70, >8.9% [>74 mmol/ mol] n=63). Baseline characteristics, including use of potential hypoglycaemic drugs, were similar between groups. During the 8 years of follow-up 151 patients died (70.6%) and HbA 1c < 7.5% (<58 mmol/mol) was strongly associated with increased mortality. The highest mortality was seen in patients with a combination of HbA 1c <7.5% (<58 mmol/mol) and QTc prolongation, with an 8 year mortality of 92.1% as compared with 48.8% in those with HbA 1c < 7.5% (<58 mmol/mol) but without QTc prolongation. Conclusion/interpretations HbA 1c <7.5% (<58 mmol/mol) in a high-risk population of patients with type 2 diabetes and foot ulcers is associated with a significantly higher mortality, particularly in patients with QTc prolongation.

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“…16 The contribution of glucose lowering to the reduction of macrovascular events in the ADVANCE and ACCORD trials appears to be minimal. It may very well be that even 90 years after insulin's introduction as a therapeutic modality we are still unclear on the drivers of cardiovascular morbidity as a chronic manifestation of DM.…”

Section: Glycemic Control and Cardiovascular Outcomesmentioning

confidence: 99%