What is the efficacy of intensive therapy for type 2 diabetes mellitus (DM)?

Updated: Oct 23, 2019
  • Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
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Answer

In the UKPDS, more than 5000 patients with type 2 diabetes were followed up for up to 15 years. Those in the intensely treated group had a significantly lower rate of progression of microvascular complications than did patients receiving standard care. Rates of macrovascular disease were not altered except in the metformin-monotherapy arm in obese individuals, in which the risk of myocardial infarction was significantly decreased.

In the 10-year follow-up to the UKPDS, patients in the previously intensively treated group demonstrated a continued reduction in microvascular and all-cause mortality, as well as in cardiovascular events, despite early loss of differences in glycated hemoglobin levels between the intensive-therapy and conventional-therapy groups. [69] The total follow-up was 20 years, half while in the study and half after the study ended.

Other, shorter studies, such as Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) and the Veterans Affairs Diabetes Trial (VADT), showed no improvement in cardiovascular disease and death with tight control (lower targets than in the UKPDS). [70, 71, 72]

In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, increased mortality was noted among the poorly-controlled patients in the intensive glycemic arm; indeed there was a 66% increase in mortality for each 1% increase in HbA1c; the best outcome occurred among patients who achieved the target of an HbA1c of less than 6%. The excess mortality between the intensive and conventional glycemic arms occurred for A1c above 7%.

Differences between the patient populations in these studies and the UKPDS may account for some of the differences in outcome. The patients in these 3 studies had established diabetes and had a prior cardiovascular disease event or were at high risk for a cardiovascular disease event, whereas patients in the UKPDS study were younger, with new-onset diabetes and low rates of cardiovascular disease.

Early, intensive, multifactorial (blood pressure, cholesterol) management in patients with type 2 diabetes mellitus was associated with a small, nonsignificant reduction in the incidence of cardiovascular disease events and death in a multinational European study. [73] The 3057 patients in this study had diabetes detected by screening and were randomized to receive either standard diabetes care or intensive management of hyperglycemia (target HbA1c < 7.0%), blood pressure, and cholesterol levels.

The benefits of intensive intervention were demonstrated in the Steno-2 study in Denmark, which included 160 patients with type 2 diabetes and persistent microalbuminuria; the mean treatment period was 7.8 years, followed by an observational period for a mean of 5.5 years. Intensive therapy was associated with a lower risk of cardiovascular events, death from cardiovascular causes, progression to end-stage renal disease, and need for retinal photocoagulation. [74]

A British study indicated that the HbA1c level achieved 3 months after the initial diagnosis of type 2 diabetes mellitus predicts subsequent mortality. In other words, according to the report, aggressive lowering of glucose after diagnosis bodes well for long-term survival. (Intensified diabetes control must be introduced gradually in newly diagnosed patients.) [75]

Another study, a review of randomized clinical trials, showed that intensive glycemic control reduces the risk of microvascular complications, but at the expense of increased risk of hypoglycemia. All-cause mortality and cardiovascular mortality in the study did not differ significantly with intensive versus conventional glycemic control; however, trials conducted in usual-care settings showed a reduction in the risk of nonfatal myocardial infarction. [76]

Overall, these studies suggest that tight glycemic control (HbA1c < 7% or lower) is valuable for microvascular and macrovascular disease risk reduction in patients with recent-onset disease, no known cardiovascular diseases, and a longer life expectancy. In patients with known cardiovascular disease, a longer duration of diabetes (15 or more years), and a shorter life expectancy, however, tighter glycemic control is not as beneficial, particularly with regard to cardiovascular disease risk. Episodes of severe hypoglycemia may be particularly harmful in older individuals with poorer glycemic control and existing cardiovascular disease.

A study by Zheng et al indicated that HbA1c levels in persons with diabetes are longitudinally associated with long-term cognitive decline, as found using a mean 4.9 cognitive assessments of diabetes patients over a mean 8.1-year follow-up period. The investigators saw a significant link between each 1 mmol/mol rise in HbA1c and an increased rate of decline in z scores for global cognition, memory, and executive function. Patients in the study had a mean age of 65.6 years. The report cited a need for research into whether optimal glucose control in people with diabetes can affect their cognitive decline rate. [77, 78]


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