• Insulin
• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials

• Endocrinology
• Diabetes & Metabolic Syndrome
• Insulin
• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials

Bruce Wolffenbuttel, MD, University of Groningen, Groningen, The Netherlands, presented results from a randomized trial that prospectively compared the glycemic control achieved using basal insulin glargine, exenatide, and metformin therapy (BET) with basal insulin glargine, bolus insulin lispro, and metformin therapy (BBT) in subjects with type 2 diabetes mellitus (T2DM). The results support BET as an alternative to BBT in some patients with T2DM [Wolffenbuttel BHR et al. EASD 2013 (abstr 1); NCT00960661].

Current treatment for T2DM with elevated HbA1C is basal insulin supplemented with prandial insulin. This regimen produces weight gain and increased episodes of hypoglycemia. Exclusion of prandial insulin and the inclusion of exenatide BID coincident with the largest meals may improve glycemic control with reduced risk of hypoglycemia. Presently, the BET and BBT regimens were evaluated in T2DM patients whose hyperglycemia was uncontrolled after 12 weeks of intensified insulin glargine treatment.

Patients (n=1036) were screened for 2 weeks. Of these, 917 patients (Table 1) entered the basal phase designed to titrate the insulin glucose dose to achieve the lowest fasting blood glucose level (target level 5.6 mmol/L) without hypoglycemia.

Six hundred thirty-seven patients unable to achieve HbA1C ≤7% (53 mmol/mol) were randomized 1:1 to the BET arm (n=316, per-protocol population [PP] n=247) and the BBT arm (n=321, PP n=263) for the 30-week treatments. The BET regimen was titrated basal insulin glargine prior to bedtime plus exenatide (5 μg BID for 4 weeks, then 10 μg BID). The BBT regimen was titrated basal insulin glargine at bedtime plus bolus insulin lispro TID titrated based on 4-point self-monitored blood glucose (premeal glucose <6.1 mmol/L, no hypoglycemia). The primary outcome was noninferiority in HbA1C change from baseline to 30 weeks for PP. Secondary outcomes were comparisons of the BET and BBT arms with respect to levels of fasting glucose, postprandial glucose, and self-monitored blood glucose, and hypoglycemia for PP.

The mean reduction in HbA1C through 30 weeks for BET was noninferior to BBT. The weight change in the BET arm (−2.4±0.3 kg) was significantly different from the BBT arm (+2.1±0.2 kg) (difference between BET and BBT −4.6 kg; 95% CI, −5.2 to −3.9; p<0.0001). The insulin lispro dose at 30 weeks in the BBT arm was 0.5±0.4 IU/kg/day. Other findings are summarized in Table 2.

The incidence of transient gastrointestinal events was higher for the BET arm versus BBT arm and included nausea (32% vs 2%), vomiting (12% vs 1%), and diarrhea (11% vs 5%). Overall, hypoglycemia, expressed as events per 100 years, was less in the BET arm than the BBT arm (minor, 206 vs 522; major, 2 vs 7; non-nocturnal, 64 vs 350), except for nocturnal events.

The data support the use of insulin glargine plus twice-daily exenatide as an alternative to a regimen involving basal insulin glargine and insulin lispro in T2DM patients with uncontrolled hyperglycemia after a regimen of intensified basal insulin glargine.

• © 2013 MD Conference Express®