Insulin and Cardiovascular Outcomes in Dysglycemia

Posted by Sara Fazio • July 27th, 2012

In a new study from the ORIGIN Trial Investigators with a 2-by-2 factorial design, patients with cardiovascular risk factors and dysglycemia or type 2 diabetes received insulin glargine or standard care. Insulin treatment did not affect cardiovascular events, the primary outcome.

An elevated fasting plasma glucose level is an independent risk factor for adverse cardiovascular outcomes. Basal insulin secretion is required to maintain fasting plasma glucose levels below 5.6 mmol per liter (100 mg per deciliter), and an elevated fasting plasma glucose level indicates that there is insufficient endogenous insulin secretion to overcome underlying insulin resistance.

Clinical Pearls

What were the primary outcomes in this study in a population of patients with impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes who were assigned to insulin glargine or standard treatment?

The incidence of both coprimary outcomes (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, or a composite of any of these events, a revascularization procedure, or hospitalization for heart failure) did not differ significantly between treatment groups, with hazard ratios of 1.02 (95% confidence interval [CI], 0.94 to 1.11; P=0.63) and 1.04 (95% CI, 0.97 to 1.11; P=0.27) for the first and second coprimary outcomes, respectively. There was also no significant difference in mortality (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P=0.70) or microvascular events (hazard ratio, 0.97; 95% CI, 0.90 to 1.05; P=0.43).

What were the results of this trial with respect to patients who had impaired glucose tolerance?

This intervention reduced incident diabetes in participants with impaired fasting glucose or impaired glucose tolerance, though it was associated with modest weight gain and more episodes of hypoglycemia. The study demonstrated that near-normal fasting plasma glucose and glycated hemoglobin levels could be achieved and maintained for more than 6 years with a daily injection of basal insulin with or without an oral agent when self-monitored fasting glucose levels were used by high-risk patients to adjust the dose of insulin glargine.

Morning Report Questions

Q: What were findings in this study with respect to secondary outcomes?

A: The analyses showed no significant difference in the incidence of any cancer (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P=0.97), death from cancer (hazard ratio, 0.94; 95% CI, 0.77 to 1.15; P=0.52), or cancer at specific sites. There was also no significant difference in angina, amputations, cardiovascular or noncardiovascular hospitalizations, motor-vehicle accidents, or fractures.

Q: What effect did insulin glargine have on the development of hypoglycemia?

A: The incidence of a first episode of severe hypoglycemia was 1.00 per 100 person-years in the insulin-glargine group and 0.31 per 100 person-years in the standard-care group (P<0.001). One death attributed to hypoglycemia occurred in a participant while taking insulin glargine. The incidence of a first episode of nonsevere symptomatic hypoglycemia that was confirmed by a self-measured glucose level of 54 mg per deciliter or less was 9.83 and 2.68 per 100 person-years in the insulin-glargine and standard-care groups, respectively (P<0.001); the incidence of any (i.e., confirmed or unconfirmed) nonsevere symptomatic hypoglycemia was 16.72 and 5.16 per 100 person-years, respectively. A total of 2689 participants in the insulin-glargine group (43%) and 4693 in the standard-care group (75%) did not have any symptomatic hypoglycemia.

Table 3. Incidence of a First Episode of Severe Hypoglycemia.

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