title: Design of FLAT-SUGAR: Randomized Trial of Prandial Insulin Versus Prandial GLP-1 Receptor Agonist Together With Basal Insulin and Metformin for High-Risk Type 2 Diabetes.
abstract: OBJECTIVE
  Glycemic variability may contribute to adverse medical outcomes of type 2 diabetes, but prior therapies have had limited success in controlling glycemic fluctuations, and the hypothesis has not been adequately tested.
  
  
  METHODS
  People with insulin-requiring type 2 diabetes and high cardiovascular risk were enrolled during a run-in period on basal-bolus insulin (BBI), and 102 were randomized to continued BBI or to basal insulin with a prandial GLP-1 receptor agonist (GLIPULIN) group, each seeking to maintain HbA(1c) levels between 6.7% and 7.3% (50-56 mmol/mol) for 6 months. The primary outcome measure was glycemic variability assessed by continuous glucose monitoring; other measures were HbA(1c), weight, circulating markers of inflammation and cardiovascular risk, albuminuria, and electrocardiographic patterns assessed by Holter monitoring.
  
  
  RESULTS
  At randomization, the mean age of the population was 62 years, median duration of diabetes 15 years, mean BMI 34 kg/m(2), and mean HbA(1c) 7.9% (63 mmol/mol). Thirty-three percent had a prior cardiovascular event, 18% had microalbuminuria, and 3% had macroalbuminuria. At baseline, the continuous glucose monitoring coefficient of variation for glucose levels was similar in both groups.
  
  
  CONCLUSIONS
  FLAT-SUGAR is a proof-of-concept study testing whether, in a population of individuals with type 2 diabetes and high cardiovascular risk, the GLIPULIN regimen can limit glycemic variability more effectively than BBI, reduce levels of cardiovascular risk markers, and favorably alter albuminuria and electrocardiographic patterns. We successfully randomized a population that has sufficient power to answer the primary question, address several secondary ones, and complete the protocol as designed.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Probstfield
authors.forename: Irl
authors.initials: I
authors.lastname: Hirsch
authors.forename: Kevin
authors.initials: K
authors.lastname: O'Brien
authors.forename: Barry
authors.initials: B
authors.lastname: Davis
authors.forename: Richard
authors.initials: R
authors.lastname: Bergenstal
authors.forename: Connie
authors.initials: C
authors.lastname: Kingry
authors.forename: Dori
authors.initials: D
authors.lastname: Khakpour
authors.forename: Sarah
authors.initials: S
authors.lastname: Pressel
authors.forename: Kelley R
authors.initials: KR
authors.lastname: Branch
authors.forename: Matthew
authors.initials: M
authors.lastname: Riddle
mesh_terms: D000419:Albuminuria / Q000188:drug therapy; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D000077270:Exenatide; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D000069036:Insulin Glargine / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use*; D019518:Postprandial Period; D012307:Risk Factors; D013997:Time Factors; D014688:Venoms / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008687:Metformin; D010455:Peptides; D014688:Venoms