10 Diabetes Studies Every Pharmacist Should Know

JULY 29, 2016
An estimated 29.1 million individuals in the United States have diabetes, and another 86 million adults have prediabetes.
Over the years, a number of landmark clinical studies have been published in the diabetes space and shaped how we treat the disease today. Here are 10 studies involving diabetes every pharmacist should know:
1. UGDP (1970)1
Launched in 1960, UGDP was one of the first large-scale, randomized clinical trials implemented in the United States. It aimed to evaluate the effectiveness of long-term antidiabetic medications in preventing or delaying vascular complications of diabetes.
A total of 823 patients 53 years, on average, were randomized into tolbutamide (a sulfonylurea), insulin standard, insulin variable, or placebo groups. Treatment with phenormin (a biguanuide) was added 18 months after recruitment was started for the other agents.
Because of an excess of cardiovascular (CV) deaths in patients treated with tolbutamide, investigators terminated this study aim before the end of follow-up. Approximately 2 years later, they also discontinued the recommendation that patients take phenformin because of higher all-cause and CV mortality.
The 2 insulin arms were continued to the end of patient follow-up, but neither were any more effective than placebo in prolonging life or delaying the onset and development of vascular complications.
Neither insulin nor the oral hypoglycemic agents assessed provided greater protection against vascular complications than diet alone. Tolbutamide and phenformin were associated with higher mortality.
2. UKPDS (1998)2,3
Prompted by UGDP’s results, this was the largest and longest study ever conducted in type 2 diabetes (T2D) patients.
It recruited 5102 newly diagnosed T2D patients in 23 centers within the United Kingdom between 1977 and 1991. Patients were followed for 10 years, on average, to determine the effect of intensive glycemic control on the incidence of vascular complications and compare the advantages and disadvantages of different antidiabetic medications (metformin, sulfonylureas, insulin). Benefits of different blood pressure (BP) targets with ACE inhibitor or beta-blocker use were also assessed.
The results showed a 25% risk reduction in microvascular endpoints in the treatment-intensive group (median HbA1C 7%) versus the conventional-treatment group (HbA1C 7.9%). Although there was a trend towards reduced macrovascular complications, it didn’t reach statistical significance. The intensive group saw more hypoglycemic episodes and weight gain than the conventional group.
No differences were detected in the rates of myocardial infarction (MI) or diabetes-related death between participants assigned sulfonylureas or insulin therapies.
In the subgroup of overweight subjects, patients assigned to intensive therapy with metformin had decreased risks of diabetes-related complications and all-cause mortality versus diet alone; this wasn’t seen with insulin or sulfonylurea treatment. 
Tight BP control reduced both diabetes-related morbidity and mortality, with each reaching statistical significance. Differences in BP were comparable between the different antihypertensives used.
Intensive glycemic control (median HbA1C 7%) in T2D was associated with a reduction in microvascular complications, but there was no statistically significant effect on macrovascular disease or mortality. 
3. ADVANCE (2009)4
This trial’s purpose was to build on information from UKPDS to determine whether a more intensive HbA1C goal ≤6.5% would provide additional benefit in reducing vascular disease risk and further investigate BP control benefit in diabetics.
This randomized, controlled trial of more than 11,000 T2D patients was conducted at 215 collaborating centers in 20 countries with a median 5-year follow-up duration.
At the end of the follow-up period, mean HbA1C values were 6.5% in the intensive-control group and 7.3% in the standard-control group. In the treatment-intense group, there was a statistically significant 10% reduction in a composite of macrovascular and microvascular events. The main contributor to this reduction was a 21% relative reduction in the risk of new or worsening nephropathy; there was no evidence of a reduction in macrovascular events.
There were no significant differences between the 2 groups in deaths, but hospitalization and severe hypoglycemia were more frequent in the intensive-control group.
For the BP analysis, use of perindopril and indapamide showed a reduction in the risks of major vascular events and death, regardless of initial BP.
Intensive glycemic control targeting HbA1C  ≤6.5% improved microvascular outcomes but had no impact on macrovascular outcomes in T2D patients. Increased hospitalized and severe hypoglycemia were potential complications of intensive control.

Timothy O'Shea, PharmD
Timothy O'Shea, PharmD
Timothy O'Shea, PharmD, is a Clinical Pharmacist working at a large health insurance plan on the east coast. Additionally he works per diem at a retail pharmacy chain. He graduated from MCPHS University - Boston in 2015 and subsequently completed a PGY-1 Managed Care Pharmacy Residency. His professional interests include pharmacy legislation and managed care pharmacy. He can be followed on Twitter at @toshea125.
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