Dynamic risk factors associated with non-severe hypoglycemia in patients treated with insulin glargine or exenatide once weekly

J Diabetes. 2015 Jan;7(1):60-7. doi: 10.1111/1753-0407.12208. Epub 2014 Dec 17.


Background: Glycemic control in patients with type 2 diabetes is a dynamic process, and changes in risk factors affecting the incidence of hypoglycemia are not well understood. This study explored the association of longitudinal interactive effects of clinical risk factors and concomitant medications on hypoglycemia risk in patients treated with insulin glargine (IG) or exenatide once weekly (EQW).

Methods: Pooled patient-level 52-week longitudinal data of treatment with EQW (n = 541) or IG (n = 223) from three controlled trials were analyzed.

Results: Proportions of patients with at least one episode of hypoglycemia in the EQW and IG groups were 23% and 54%, respectively. Compared with patients with HbA1c ≥7% (53 mmol/mol) over time, patients with HbA1c <7% had significantly higher hypoglycemia risk in both groups (95% confidence intervals [CI] of odds ratios [OR]: EQW-1.21, 2.81; IG- 6.26, 9.84). The patterns of interaction effect of changing body mass index (BMI) and HbA1c on hypoglycemia risk differed in the two treatment groups: patients with with BMI >35 kg/m(2) had a 119% increased hypoglycemia risk in the EQW group, but a 57% reduced risk in the IG group. Sulfonylurea-treated patients in the EQW and IG groups had 4.7- and 3-fold additional hypoglycemia risk, respectively, versus non-sulfonylurea-treated patients.

Conclusion: This study revealed differential effects of tight glycemic control and itsinteraction with treatment-induced changes in BMI on hypoglycemia risk its interaction in patients treated with EQW and IG. The residual adverse effect of sulfonylurea was higher in EQW-treated patients.

Keywords: glucagon-like peptide-1 receptor agonist; hypoglycemia risk factors; insulin glargine; tight glycemic control and body weight interaction; 关键词:胰高血糖素样肽-1受体激动剂,低血糖危险因素,甘精胰岛素,严格血糖控制与体重的相互作用.

MeSH terms

  • Blood Glucose / analysis
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Exenatide
  • Female
  • Humans
  • Hypoglycemia / chemically induced*
  • Hypoglycemic Agents / adverse effects*
  • Insulin Glargine
  • Insulin, Long-Acting / adverse effects*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Peptides / adverse effects*
  • Risk Factors
  • Venoms / adverse effects*


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin, Long-Acting
  • Peptides
  • Venoms
  • Insulin Glargine
  • Exenatide