Getting to goal in newly diagnosed type 2 diabetes using combination drug “subtraction therapy”

• Published in: Metabolism, clinical and experimental clinical and experimental, 2015-09, Vol.64 (9), p.1005-1012
• Main Authors: Jennings, Anthony S, Lovett, Alexandra J, George, Tina M, Jennings, Jonathan S
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Carbamates - therapeutic use; Combination drug therapy; Diabetes Mellitus, Type 2 - drug therapy; Drug Therapy, Combination; Durability; Endocrinology & Metabolism; Female; Follow-Up Studies; Glycated Hemoglobin A - analysis; Glycated Hemoglobin A - metabolism; Goals; Humans; Hypoglycemia - epidemiology; Hypoglycemia - etiology; Hypoglycemic Agents - therapeutic use; Male; Metformin - therapeutic use; Middle Aged; Piperidines - therapeutic use; Subtraction therapy; Thiazolidinediones - therapeutic use; Treatment efficacy; Treatment Outcome; Type 2 diabetes
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2015.04.008

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.