Surgery or Lifestyle With Intensive Medical Management in the Treatment of Type 2 Diabetes
Condition: Type 2 Diabetes Mellitus; Obesity
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      There is substantial clinical evidence regarding the safety and efficacy of currently
      practiced bariatric surgical techniques to improve metabolic control and/or resolve type 2
      diabetes (T2DM) in clinically severe obese patients (class 3 obesity). Evidence suggests such
      procedures have greater effects on insulin secretion and insulin action than that expected
      from weight loss alone, which has led to the recent claim that such procedures may be useful
      as a primary treatment for T2DM in the moderately obese population. Concurrently, there have
      also been substantial advances in the non-surgical medical management of T2DM. As a result,
      the best treatment algorithm for T2DM patients with class 1 & 2 obesity is increasingly
      controversial. This trial investigates the utility of currently practiced and available
      bariatric surgical procedures as compared with multidisciplinary intensive medical and weight
      management for the treatment of T2DM with class 1 and 2 obesity.
    

Detailed description: 
      Primary Specific Aim 1: To evaluate the effectiveness of laparoscopic adjustable gastric band
      versus intensive medical and weight management in the treatment of T2DM.

      There has been only one randomized control trial to date comparing surgical to medical
      management of T2DM in the less obese population, which demonstrated substantial superiority
      of the laparoscopic adjustable gastric band (LAGB) in the improvement of glycemic and
      metabolic measures. However, these findings remain controversial as the magnitude of weight
      loss in this study was far superior to that generally reported following LAGB. Thus, we
      propose a second prospective randomized trial to evaluate the effectiveness of intensive
      medical and weight management (IMWM) vs. LAGB in T2DM patients with BMI in the 30-42 kg/m^2
      range. This range does extend LAGB surgery to BMI limits below those currently used in
      medical care, FDA Investigational Device Exemption (IDE) G090163. The primary outcome
      variable will be attaining glycemic control (as defined by fasting plasma glucose levels <126
      mg/dL and HbA1c <6.5%) at one year of follow-up. The study was subsequently extended to 3
      years, with the same outcome measures.

      Primary Specific Aim 2: To evaluate the effectiveness of laparoscopic Roux-en-Y gastric
      bypass versus intensive medical and weight management in the treatment of T2DM.

      Although observational studies and meta-analyses suggest rapid and sustained improvement or
      resolution of diabetes following laparoscopic Roux-en-Y gastric bypass (LRYGB), to date there
      has been no randomized trial directly comparing these effects to those produced by IMWM. We
      propose a prospective randomized trial comparing the effectiveness of IMWM vs. LRYGB in T2DM
      patients with BMI's in the 30-42 kg/m^2 range. This range extends LRYGB surgery to BMI limits
      below those currently used in medical care to explore the use of this type of surgical
      procedure in type 2 diabetes with lesser magnitude obesity. The primary outcome variable will
      be attaining glycemic control (as defined by fasting plasma glucose levels <126 mg/dL and
      HbA1c <6.5%) at one year of follow-up. The study was subsequently extended to 3 years, with
      the same outcome measures.

      The trial is designed to allow for strong patient preference towards specific surgical
      procedures, and as such is designed as two parallel trials with each of the two surgical
      procedures judged against intensive medical weight management. Subjects without strong
      preference will be randomly assigned to one of the four study arms.

      Secondary Specific Aims:

      Determination of suitable study design: In addition to testing the effectiveness of current
      and available surgical techniques as compared to medical management, this trial will also
      test the utility of this trial design in future multi-institutional comparative effectiveness
      studies of these therapies, or alternatively, in future trials evaluating new surgical
      procedures being designed specifically for less obese T2DM patients.

      Measurement of metabolic factors: Insulin secretion and action will be assessed during
      provocative mixed meal tolerance tests (MMTT) using the corrected incremental insulin
      response (CIR) and the composite insulin sensitivity index (CISI). MMTT will be performed in
      all groups at baseline and repeated at the time point of 10% weight loss (matched for weight
      loss), and at 12 months following randomization (matched for time).

      Measurement of cardiovascular risk factors: Each group will be studied for evidence of
      changes in cardiovascular disease risk factors. Multiple surrogate measures of cardiovascular
      health will be compared, including blood pressure, fasting lipid profiles,
      endothelium-dependent vasodilatation and plasma will be collected for circulating markers of
      endothelial function. The study was subsequently extended to 3 years, with the same outcome
      measures.

      Measurement of metabolic rate: Each group will be studied for change in energy expenditure
      and respiratory quotient using the non-invasive indirect calorimetry technique.

      Quality of life and cost utility outcomes: Longitudinal measures of patient reported quality
      of life outcomes, and cost utility measures will also be collected to generate preliminary
      data for future studies.
    

Intervention name(s): Allergan Adjustable Gastric Band Surgery; Intensive Medical Diabetes & Weight Management (Why WAIT) - Band Group; Roux-en-Y Gastric Bypass (RYGB) Surgery; Intensive Medical Diabetes & Weight Management (Why WAIT) - Bypass Group
Intervention type(s): Device; Other; Procedure; Other
Intervention description(s): Intensive Medical Diabetes & Weight Management (Why WAIT) - Band Group; Intensive Medical Diabetes & Weight Management (Why WAIT) - Bypass Group
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Type 2 Diabetes Mellitus; Obesity; Lifestyle; Bariatric Surgery; Laparoscopic Adjustable Gastric Band; Laparoscopic Roux-en-Y Gastric Bypass