title: Randomized Controlled Study of Metformin and Sitagliptin on Long-term Normoglycemia Remission in African American Patients With Hyperglycemic Crises.
abstract: After intensive insulin treatment, many obese African American patients with new-onset diabetic ketoacidosis (DKA) and severe hyperglycemia are able to achieve near-normoglycemia remission. The optimal treatment to prevent hyperglycemic relapses after remission is not known.
  
  
  
  This prospective, 4-year, placebo-controlled study randomly assigned 48 African American subjects with DKA and severe hyperglycemia to metformin 1,000 mg daily (n = 17), sitagliptin 100 mg daily (n = 16), or placebo (n = 15) after normoglycemia remission. Hyperglycemic relapse was defined as fasting glucose >130 mg/dL (7.2 mmol/L) and HbA1c>7.0% (53 mmol/mol). Oral glucose tolerance tests were conducted at randomization and at 3 months and then every 6 months for a median of 331 days. Oral minimal model and incremental area under the curve for insulin (AUCi) were used to calculate insulin sensitivity (Si) and β-cell function, respectively. Disposition index (DI) was calculated as a product of Si and incremental AUCi.
  
  
  
  Relapse-free survival was higher in sitagliptin and metformin (P = 0.015) compared with placebo, and mean time to relapse was significantly prolonged in the metformin and sitagliptin groups compared with the placebo group (480 vs. 305 days, P = 0.004). The probability of relapse was significantly lower for metformin (hazard ratio 0.28 [95% CI 0.10-0.81]) and sitagliptin (0.31 [0.10-0.98]) than for placebo. Subjects who remained in remission had a higher DI (P = 0.02) and incremental AUCi (P < 0.001) than those with hyperglycemia relapse without significant changes in Si.
  
  
  
  This study shows that near-normoglycemia remission was similarly prolonged by treatment with sitagliptin and metformin. The prolongation of remission was due to improvement in β-cell function.
authors: Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA pvellan@emory.edu.
authors: Priyathama
authors: P
authors: Vellanki
authors: Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA.
authors: Dawn D
authors: DD
authors: Smiley
authors: School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.
authors: Darko
authors: D
authors: Stefanovski
authors: Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA.
authors: Isabel
authors: I
authors: Anzola
authors: Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA.
authors: Wenlan
authors: W
authors: Duan
authors: Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA.
authors: Megan
authors: M
authors: Hudson
authors: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA.
authors: Limin
authors: L
authors: Peng
authors: Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA.
authors: Francisco J
authors: FJ
authors: Pasquel
authors: Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA.
authors: Guillermo E
authors: GE
authors: Umpierrez
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D016883:Diabetic Ketoacidosis / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy; D011446:Prospective Studies; D016037:Single-Blind Method; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin; D000068900:Sitagliptin Phosphate