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Intensive Therapy in Newly Diagnosed Type 2 Diabetes
  1. Lindsay B. Harrison, MD*,
  2. Beverley Adams-Huet, MS†‡,
  3. Xilong Li, PhD, MS,
  4. Philip Raskin, MD*,
  5. Ildiko Lingvay, MD, MPH, MSCS
  1. From the Divisions of *Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, †Biostatistics, Department of Clinical Sciences, ‡Mineral Metabolism, Department of Internal Medicine, and §Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, TX.
  1. Received December 2, 2013, and in revised form January 19, 2014.
  2. Accepted for publication January 23, 2014.
  3. Reprints: Ildiko Lingvay, MD, MPH, MSCS, Division of Endocrinology, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8857. E-mail: Ildiko.Lingvay{at}
  4. Partly supported by an investigator-initiated trial grant from Novo Nordisk, Inc to I.L. Novo Nordisk, Inc played no role in the study design, conduct, or analysis, nor in preparation or final approval of the article. I.L. was supported by NIH 1K23RR024470 and B.A.H. by NIH UL1RR024982. L.B.H., B.A.H., and X.L. have nothing to declare. I.L. serves on the scientific advisory board of Novo Nordisk, Inc and has received research funding, payable to the University of Texas Southwestern Medical School, from Novo Nordisk and GI Dynamics. P.R. has received research support, payable to the University of Texas Southwestern Medical Center, from Amgen Inc, Amylin Pharmaceuticals, Andromeda Biotech Ltd, AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim Pharmaceuticals, Gilead Sciences Inc, Intarcia, Eli Lilly and Company, Novo Nordisk, Pfizer Inc, Reata Pharmaceuticals, and Rhythm Pharmaceuticals Inc. P.R. is an advisor of Amgen and Janssen and is on the Speakers’ Bureau for Janssen. No other potential conflicts of interest relevant to this article were reported.

Results of a 6-Year Randomized Trial


Background This study aimed to assess the efficacy of early intensive diabetes therapy with either insulin plus metformin (INS) or triple oral therapy (TOT) with metformin, glyburide, and pioglitazone on glycemic control and A-cell function.

Methods Fifty-eight treatment-naive newly diagnosed patients with type 2 diabetes underwent a 3-month lead-in treatment period with insulin and metformin, then were randomized to INS or TOT for 6 years. β-Cell function was measured using mixed-meal challenge test. β-Cell function remained stable throughout the 6-year study in both groups, as measured by the C-peptide area under the curve (AUC; P = 0.13), the AUC C-peptide/AUC glucose (P = 0.9), and by the disposition index (P = 0.8). Excellent glycemic control was maintained in both groups (end-of-study hemoglobinA1c, 7.3% [SD, 1.7%] INS vs 6.4% [1.4%] TOT; P = 0.4). There were 8 treatment failures (confirmed hemoglobinA1c, 98%) in INS and 6 in TOT (P = 0.93). The predictors of treatment failure included higher fasting glucose (P = 0.008), fasting C-peptide (P = 0.008), systolic blood pressure (P = 0.004), and lower insulin sensitivity (P = 0.04) at randomization.

Conclusions Early intensive treatment at the time of type 2 diabetes diagnosis—initial short-term insulin treatment followed by either insulin-based or intensive oral hypoglycemic–based therapy—stabilizes β-cell function for at least 6 years. Treatment failure was independent of intervention and was associated with worse disease pathology at baseline.

Key Words
  • β-cell function
  • type 2 diabetes
  • insulin treatment
  • triple oral hypoglycemic therapy
  • HbA1c
  • glycemic control
  • mixed-meal challenge test
  • insulin resistance
  • hypoglycemia
  • weight gain
  • quality of life

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