Lowest Glucose Variability and Hypoglycemia Are Observed With the Combination of a GLP-1 Receptor Agonist and Basal Insulin (VARIATION Study)

Diabetes Care. 2017 Feb;40(2):194-200. doi: 10.2337/dc16-1582. Epub 2016 Dec 2.

Abstract

Objective: There is a dearth of published literature comparing glucose variability (GV) between different insulin regimens in type 2 diabetes. This cohort study compares GV using continuous glucose monitoring (CGM) in patients with well-controlled type 2 diabetes using four common insulin regimens: basal insulin + oral drugs (BO), basal insulin + glucagon-like peptide 1 receptor agonist (GLP-1 RA) (BGLP), premixed insulin (PM), and basal-bolus insulin (BB).

Research design and methods: Consecutive patients from three endocrinology clinics who met study criteria-type 2 diabetes, age 18 to 80 years, BMI ≤ 45 kg/m2, stable insulin regimen for a minimum of 6 months, and stable A1C value ≤7.5% (58 mmol/mol) before study enrollment-underwent 6-day masked CGM. Hypoglycemia was defined as a sensor glucose concentration <70 mg/dL on CGM.

Results: A total of 160 patients with comparable baseline characteristics formed four equal insulin regimen cohorts. The daily glucose SD (the primary outcome) was significantly lower in the BGLP cohort versus the BO, PM, and BB cohorts (P = 0.03, P = 0.01, and P < 0.01, respectively), and remained so after adjusting for age, BMI, type 2 diabetes duration, and A1C. Similarly, daily hypoglycemia outcomes on CGM were least for the BGLP cohort.

Conclusions: The lowest GV and lowest hypoglycemia were observed in patients using the combination of basal insulin with a GLP-1 RA, supporting the complementary glycemic action of these agents in type 2 diabetes. These observed benefits in GV and hypoglycemia may contribute to the cardiovascular outcome reduction seen with GLP-1 RA therapy and should be investigated further.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Glucose / metabolism*
  • Blood Glucose Self-Monitoring
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / drug therapy
  • Endpoint Determination
  • Female
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / epidemiology*
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacology*
  • Incidence
  • Insulin / blood
  • Insulin / pharmacology*
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Blood Glucose
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin