Bariatric Surgery vs Lifestyle Intervention for Diabetes Treatment

5-Year Outcomes From a Randomized Trial

Anita P. Courcoulas; James W. Gallagher; Rebecca H. Neiberg; Emily B. Eagleton; James P. DeLany; Wei Lang; Suriya Punchai; William Gourash; John M. Jakicic

Disclosures

J Clin Endocrinol Metab. 2020;105(3) 

In This Article

Materials and Methods

Study Design

The design, methods, and rationale of this study have been previously reported.[9,10] The study protocol was reviewed and approved by the University of Pittsburgh Institutional Review Board. Briefly, the trial was a prospective, single institution, randomized clinical trial with stratification by gender and baseline BMI. There were 3 treatment arms that compared the efficacy for treating T2DM: RYGB or LAGB followed by LLLI in years 2 to 5, and LWLI in year 1 then 4 years of LLLI. The inclusion criteria were adults aged 25 to 55 years with a BMI of 30 to 40 kg/m2 and a diagnosis of T2DM confirmed by fasting plasma glucose (FPG) level of greater than 125 mg/dL and/or treatment with at least 1 glucose-lower medication.[10] All patients provided written informed consent. The 61 participants randomized, treated, and followed (20 RYGB + LLLI, 21 LAGB + LLLI, 20 LWLI + LLLI) in the initial and second phase of the trial were also eligible and included in this third phase of the study.

Intervention

After conducting 1-year follow-up (initial phase),[10] the study participants provided informed consent for an additional 2 years (second phase)[9] of annual visits and a structured LLLI, which was subsequently extended an additional 2 years for 5 years of total follow-up for all 3 groups (RYGB + LLLI, LAGB + LLLI, and LWLI + LLLI) in this third phase of the study. While the study physician monitored all laboratory data including glucose levels for safety according to protocol guidelines, the management all individuals' T2DM was driven by their original treating endocrinologist or primary care physician. The first year of the intensive lifestyle LWLI arm and the LLLI for all 3 arms were developed from the Diabetes Prevention Program and the Look AHEAD trial, customized for patients treated with a surgical intervention.[11–13] After the first year of follow-up, the postsurgical patients (RYGB and LAGB) were provided instruction on the behavioral changes for weight control that participants in the LWLI were taught during their year 1 intervention. The LLLI for all groups comprised an in-person session (approximately 30–40 minutes) and a brief telephone call (less than 10 minutes) per month plus regular refresher group meetings. At each meeting, a specific behavioral change concept related to weight loss was targeted. If a participant was unable to attend the in-person session, a telephone call was utilized, and relevant materials were mailed to the individual.

Study Outcomes

The priori-defined primary and secondary endpoints for this trial was to conduct a 1-year feasibility study (initial phase).[10] Subsequent follow-up assessments after the first year were therefore exploratory. The primary outcomes in this 5-year follow-up report mirrored those reported in the 3-year outcomes paper and include either partial or complete remission of T2DM.[9] Remission of T2DM was defined by the American Diabetes Association criteria, which classifies partial remission as absence of any medications for diabetes with hemoglobin A1c (HbA1c) level < 6.5% and FPG ≤ 125 mg/dL.[14] Complete remission was defined as absence of medications with HbA1c <5.7% and FPG ≤ 100 mg/dL.[14] Secondary outcomes included glycemic control and medications, weight change, lipid profile changes, blood pressure, and adverse events. Glycemic control (defined by same FPG and HbA1c), and the use of glucose-lowering medications (4 categories: none, insulin only, insulin/other medication, oral/other medication) were recorded prior to initial treatment and then at each annual follow-up visit. Baseline measurements of weight, including calculation of BMI (weight in kilograms divided by square of height in meters) and waist circumference. Blood was drawn for a lipid profile (high- and low-density lipoproteins, triglycerides, and total cholesterol) at each visit. Blood pressure was measured twice at each visit and averaged. Adverse events of any type requiring medical treatment were also recorded in detail at each visit.

Statistical Analysis

Statistical analyses were performed using SAS (version 9.4) with the type I error rate fixed at 0.05 (2-tailed). Categorical variables are summarized using frequencies and percentages. Continuous variables with normal distributions are presented as mean (±standard deviation); continuous variables with non-normal distributions are presented as medians and interquartile ranges. Differences in baseline characteristics among the RYGB, LAGB, and LWLI groups were examined using the Pearson's chi-square test or Fisher's exact test for categorical variables and analysis of variance or Kruskal–Wallis test for continuous variables.

Changes in continuous outcomes from baseline to 12, 24, 36, 48, and 60 months were analyzed using mixed effects models with covariate adjustment for randomization stratification factors (gender and baseline BMI). Percent change in weight was adjusted for baseline weight. Inferences focused on the overall treatment effect, time, and treatment by time interaction. Pairwise comparisons were made between treatment groups at 60 months. For each outcome, 3 pairwise comparisons were made among the 3 treatment groups at 60 months, with the significance level set at .0167 (=.05/3) using the Bonferroni correction to account for multiple comparisons. Least-square means, along with their standard errors, were obtained from the models. Intent-to-treat analyses were conducted using multiple imputation using SAS PROC MI and PROC MIANALYZE. For each outcome, 10 datasets were imputed, and results were combined. For the primary endpoints of partial T2DM remission and complete remission, as well as other categorical data such as medication category usage, the Fisher's exact test was used to compare differences among groups at given time point. The intention-to-treat approach was used in analyses of the primary endpoint assuming no remission for participants that did not return for follow-up.

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