A Narrative Review of Diabetes Intervention Studies to Explore Diabetes Care Opportunities for Pharmacists

Table 1

Summary of landmark diabetes trials.

Trials	Number of patients	Country (ethnicity)	Measure	Outcome
UKPDS	5102	UK	(1) Intensive blood glucose control using metformin (to achieve HbA1c of 7%) versus conventional treatment. Patient followed up for median of 10.7 years; (2) Intensive BP control (less than 150/85 mm Hg); (3) Efficacy of captopril or atenolol as antihypertensive and in controlling microvascular and macrovascular complications	(1) A reduction of 1% in HbA1c produced significant risk reduction (12%) for any diabetes related end point, 25% risk reduction for microvascular end points, 21% risk reduction for retinopathy and 33% risk reduction for albuminuria at 12 years, and 16% risk reduction for myocardial infarction; (2) Significant effect on microvascular and macrovascular complications; (3) Captopril and atenolol were equally effective antihypertensives in preventing microvascular and macrovascular complications
ADVANCE	10000	20 countries from Asia, Europe and North America, and Australia	Intensive lowering of blood glucose to HbA1c of 6.5% (gliclazide modified release) in addition to other therapies and BP (perindopril/indapamide combination) compared to UKPDS trial; Median follow-up of 5 years	(1) Significant reduction in microvascular events; (2) Severe and minor hypoglycemia more frequent in intensive arm; (3) Hospitalisation more frequent in intensive arm
DCCT	1441	USA and Canada	Intensive therapy using three or more daily injections compared to conventional treatment (one or two insulin injections daily) among type 1 diabetes patients; Mean follow-up of 6.5 years	(1) Intensive therapy reduced microalbuminuria: 39%, albuminuria: 54%, neuropathy: 60%, progression of retinopathy: 54%, and risk of retinopathy: 76%; (2) Significant weight gain and diabetic ketoacidosis were reported more on intensive arm
ACCORD	(1) 10251; (2) 4733; (3) 5518	USA and Canada	(1) Intensive intervention to control hyperglycemia to less than HbA1c of 6.0%; (2) Two targets for systolic levels in BP control (<120 versus <140); (3) Two regimens for plasma lipid levels. Fenofibrate and simvastatin versus simvastatin alone; Mean follow-up of 3.4 years	(1) All cause mortality was significantly greater in the intensive arm; (2) No reduction in macrovascular, mortality, or myocardial infarctions; (3) No significant difference between the two arms
VADT	1791	USA	Comparison between intensive and standard glucose control; Mean follow-up of 5.6 years	(1) No significant difference in the rates of CVD events, death, or microvascular complications; (2) More hypoglycemia in intensive group

Note: HbA1c (glycated hemoglobin) reflects average plasma glucose over the previous eight to 12 weeks. It is used as a marker for diabetes control [19].
The ACCORD trial is divided into three different groups of patients, namely, the glycemic, lipid, and blood pressure groups.