title: Getting to goal in newly diagnosed type 2 diabetes using combination drug "subtraction therapy".
abstract: BACKGROUND
  The treatment of newly diagnosed type 2 diabetes mellitus is diverse, with no clear consensus regarding the initial drug regimen or dosing to achieve optimal glycemic control.
  
  
  METHODS
  We treated 44 consecutive patients with newly diagnosed type 2 diabetes with maximally tolerated doses of pioglitazone 45 mg/day, metformin 1000-2000 mg/day, and repaglinide 1-4 mg before meals. The doses and drugs were subsequently decreased ("subtraction therapy") to achieve optimal glycemic control and minimize side effects. Three primary outcomes were measured: the short term HbA1c response, the long term HbA1c response, and the incidence of hypoglycemia.
  
  
  RESULTS
  All 44 patients responded with a rapid, progressive decline in their HbA1c levels from 11.43±2.3% to 6.17±0.72% (101±25.1 mmol/mol to 44±7.9 mmol/mol) by three months, and remained stable thereafter. An HbA1c ≤7.0% (≤53 mmol/mol) was reached within 1-4 months in 42 of 44 patients, and in every patient by 12 months. Each patient's lowest HbA1c level, 5.65±0.6% (38±6.6 mmol/mol), was reached over 6.3±2.9 months. Patients with initial HbA1c levels >10% (>86 mmol/mol) (n=33) responded similarly as those with HbA1c levels <10% (<86 mmol/mol) (n=11). Combination drug therapy maintained HbA1c levels between 5.0 and 7.0% (31 and 53 mmol/mol) for up to 14.83 years. Only one clinically significant hypoglycemic event occurred during 261.08 person-years of follow-up.
  
  
  CONCLUSIONS
  In our experience, combination drug "subtraction therapy" was safe and effective for treating all newly diagnosed type 2 diabetic patients.
authors.affiliation: Virtua Health System, Covered Bridge Medical Center, 27 Covered Bridge Rd., Cherry Hill, NJ, 08034. Electronic address: anthonysjennings111@gmail.com.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Jennings
authors.affiliation: Harvard Neurology Partners Program, Massachusetts General Hospital/Brigham and Women's Hospital, 55 Fruit St., WACC 720, Boston, MA, 02114.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Lovett
authors.affiliation: Virtua Health System, Covered Bridge Medical Center, 27 Covered Bridge Rd., Cherry Hill, NJ, 08034.
authors.forename: Tina M
authors.initials: TM
authors.lastname: George
authors.affiliation: Virtua Health System, Covered Bridge Medical Center, 27 Covered Bridge Rd., Cherry Hill, NJ, 08034.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Jennings
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002219:Carbamates / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis / Q000378:metabolism; D006040:Goals; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology / Q000209:etiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D000077205:Pioglitazone; D010880:Piperidines / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D002219:Carbamates; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000077205:Pioglitazone; D010880:Piperidines; D045162:Thiazolidinediones; C072379:repaglinide
keywords: Combination drug therapy; Durability; Subtraction therapy; Treatment efficacy; Type 2 diabetes