Following 84 weeks of treatment, patients with type 2 diabetes who received exenatide once weekly experienced better glycemic control with sustained overall weight loss and a lower risk of hypoglycemia, compared with those who received insulin glargine.
The findings come from an extended trial of a previously reported, 26-week, open-label trial of exenatide once weekly (EQW, marketed as Bydureon) compared with insulin glargine (IG) in patients with type 2 diabetes who failed to maintain sufficient glycemic control using metformin alone or in combination with sulfonylurea (Lancet 2010; 375:2234-43).
"These results, coupled with the significantly lower incidence of hypoglycemia observed with EQW compared with IG therapy, suggest that EQW can be a therapeutic option for patients with type 2 diabetes for whom the convenience of once-a-week dosing, weight loss, and reduction of risk for hypoglycemia are important," Dr. Michaela Diamant of the diabetes center at Free University Medical Center, Amsterdam, and associates reported in the April 2012 issue of Diabetes Care.
For the current study, the researchers enrolled 390 of the 415 patients who completed the 26-week trial, and followed them for a total of 84 weeks, which made this the longest controlled trial of EQW reported to date. The patients were randomly assigned to add EQW (2 mg) or once-daily IG (10 IU/day) to their existing blood glucose–lowering regimen.
The key efficacy measure was change in HbA1C level from baseline to study treatment end point (defined as the last nonmissing postbaseline measurement prior to any change to treatment regimen after week 48). Secondary measures included the proportion of patients achieving HbA1C targets of less than 7.0% and 6.5% or lower; change in body weight; and fasting serum lipids (Diabetes Care 2012;35:683-9).
After 84 weeks, the change in HbA1C levels from baseline to end point was significantly greater among patients in the EQW group, compared with those in the IG group (–1.2% vs. –1.0%, respectively; P = .029). A greater proportion of patients in the EQW group reached HbA1C levels of less than 7.0% at 84 weeks (44.6% vs. 36.8% among patients in the IG group), although this difference did not reach statistical significance (P = .084). However, a significantly greater proportion of patients in the EQW group reached HbA1C levels of 6.5% or less (31.3% vs. 20.2% among patients in the IG group; P = .009).
Effects on body weight significantly favored patients in the EQW group, who lost a mean of 2.1 kg from baseline to end point, whereas their counterparts in the IG group gained a mean of 2.4 kg (P less than .001).
The mean time to failure to maintain glycemic control was significantly longer for patients taking EQW than for those taking IG (57 weeks vs. 47 weeks; P = .0007).
Among the subgroup of study participants who were taking metformin plus sulfonylurea, the incidence of minor hypoglycemia was significantly lower in the EQW group, compared with the IG group (24% vs. 54%, respectively; P less than .001). A similar effect was observed among the subgroup of patients who were taking metformin alone (8% vs. 32%; P less than .001).
Nasopharyngitis was the most common adverse event (AE) that occurred in 5% or more of all study participants, affecting 21% of patients in the EQW group and 23% of patients in the IG group, a difference that was statistically similar. Diarrhea occurred more frequently in the EQW group, compared with the IG group (12% vs. 6%; P less than .05), as did nausea (15% vs. 1%; P less than .05).
"In general, after 26 weeks, new cases of AEs slowed compared with the period of time between baseline and 26 weeks," the researchers observed. "This is noteworthy with regard to nausea and vomiting, a typical AE of exenatide therapy. Our observation is consistent with several clinical trials of exenatide twice daily, which showed decreased gastrointestinal distress over time. There were some AEs that emerged only after 26 weeks of therapy. Among the most prevalent were injection site nodule at 6% of the EQW group and bronchitis, cough, and toothache at [approximately] 5% of the IG group."
Dr. Diamant and her associates acknowledged certain limitations of the study, including the "open-label nature of the design" and the fact that the study population was predominately white. "It should be noted that [approximately] 30% of patients in both groups required a reduction from baseline in their sulfonylurea dose. Although a reduction in sulfonylurea dose may reduce the risk of hypoglycemia, such a change in sulfonylurea dose may be associated with a negative impact on glucose control. In addition, the possibility for bias introduced through patient self-selection for continuation into the extension study exists."