Efficacy and safety of exenatide administered before the two largest daily meals of Latin American patients with type 2 diabetes

ABSTRACT

Objective: To evaluate whether exenatide administered before breakfast and dinner (BD) or before lunch and dinner (LD) provided similar glycemic control in Latin American patients with type 2 diabetes mellitus (T2DM) who consume a small breakfast.

Methods: In this open-label, 2-arm study, patients taking metformin, sulfonylureas, and/or thiazolidinediones were randomized to exenatide before BD or before LD (5-μg exenatide for 4 weeks, then 10-μg exenatide for 8 weeks). Treatment assignment was determined by a computer-generated random sequence using an interactive response system. Patients were eligible for study inclusion if they consumed <15% of their total caloric intake at breakfast. The primary endpoint was HbA_1c change from baseline to endpoint. Secondary endpoints included fasting serum glucose (FSG) level, 7-point SMBG profile, and safety. Clinicaltrials.gov Identifier: NCT00359879.

Results: 377 participants (55% female, age 54 ± 10 years, weight 82 ± 15 kg, BMI 31 ± 4 kg/m2, HbA_1c 8.4 ± 0.9% mean ± SD) from Brazil and Mexico were randomized to study treatment. HbA_1c reduction with exenatide administration before BD was non-inferior to administration before LD (mean difference between (LD–BD) treatments: 0.14% 95% CI –0.04 to 0.32%,p = 0.120). Both treatments resulted in statistically significant HbA_1c reductions at endpoint (BD –1.2% and LD –1.1%, respectively, p < 0.001). In Brazil, the non-inferiority criteria were met for HbA_1c reduction between treatment arms (−0.12% CI −0.37 to 0.13%, p = 0.344), whereas in Mexico, there was a difference favoring exenatide administration before BD (0.41% CI 0.16 to 0.66%, p = 0.002). At endpoint, there were no statistical significant differences between the BD and LD arms in mean change in FSG (0.50 mmol/L; CI −0.02 to 1.02 mmol/L, p = 0.058) and daily mean change in SMBG (0.19 mmol/L; CI −0.17 to 0.54 mmol/L, p = 0.295). The rates of symptomatic hypoglycemia (5.2 events/patient-year vs. 6.1 events/patient-year) and nausea (23% vs. 25%), were similar between the BD and LD arms, respectively. A limitation of the study design was that caloric intake of patients and meal times were not monitored.

Conclusions: In T2DM patients who consume a small breakfast, exenatide administration before breakfast or lunch resulted in significant improvement in glycemic control.

Key Words::

• Breakfast
• Dinner
• Exenatide
• Latin America
• Type 2 diabetes

Acknowledgments

Declaration of interest: This study was supported by Amylin Pharmaceuticals and Eli Lilly & Co. M.B.Y., M.C.J., R.G.B., and J.H.O. are employees and stock holders of Eli Lilly and Company. The authors thank the study site investigators: Antonio Roberto Chacra, São Paulo, SP; José Egídio Paulo de Oliveira, Rio de Janeiro, RJ; Rosangela Rea, Curitiba, PR; Bruno Geloneze, Campinas, SP; Adriana Costa Forti, Fortaleza, CE; Cristina Façanha, Fortaleza, CE; João Eduardo Salles, São Paulo, SP; Nelson Rassi, Goiânia, GO; Antonio Carlos Pires, São José do Rio Preto, SP; Jorge Luiz Gross, Porto Alegre, RS; Carla Daltro, Salvador, BA; Hugo Laviada, Mérida, YC; Miguel Angel Guillén, Mexico City, DF; Eduardo García García, Mexico City, DF; Gerardo González, Monterrey, NL; Pedro García, Monterrey, NL; Guillermo González, Guadalajara, JA; Eduardo Márquez, Guadalajara, JA; Ricardo Choza, Aguascalientes, AG; and Ricardo Hernández, San Luis Potosí, SL for their valuable expertise and contribution in conducting the study. The authors also thank Erika B. Parente, Marino Fernández Martínez, Gabriella Beck, Juliana Tosta, Bruno Fonseca Marçal, Juliana Uehara, Diana Verónica García Rojas, and Iris Rodríguez for their contributions in helping coordinate the study in Brazil and Mexico. Tania Miles, Eli Lilly & Company, provided editorial assistance with the manuscript figures. The authors also gratefully acknowledge all the patients who volunteered to participate.

Notes

* The results of the trial were presented in part at the American Diabetes Association's 68th Scientific Session, San Francisco, CA, USA, June 2008