Gastric bypass versus best medical treatment for diabetic kidney disease: 5 years follow up of a single-centre open label randomised controlled trial.

Background: We compared the albuminuria-lowering effects of Roux-en-Y gastric bypass (RYGB) to best medical treatment in patients with diabetic kidney disease and obesity to determine which treatment is better. Methods: A 5 year, open-label, single-centre, randomised trial studied patients with diabetic kidney disease and class I obesity after 1:1 randomization to best medical treatment (n = 49) or RYGB (n = 51). The primary outcome was the proportion of patients achieving remission of microalbuminuria after 5 years. Secondary outcomes included improvements in diabetic kidney disease, glycemic control, quality of life, and safety. For efficacy outcomes, we performed an intention-to-treat (ITT) analysis. This study was registered with ClinicalTrials.gov, NCT01821508. Findings: 88% of patients (44 per arm) completed 5-year follow-up. Remission of albuminuria occurred in 59.6% (95% CI = 45.5-73.8) after best medical treatment and 69.7% (95% CI = 59.6-79.8) after RYGB (risk difference: 10%, 95% CI, -7 to 27, P = 0.25). Patients after RYGB were twice as likely to achieve an HbA1c ≤ 6.5% (60.2% versus 25.4%, risk difference, 34.9%; 95% CI = 15.8-53.9, P < 0.001). Quality of life after five years measured by the 36-Item Short Form Survey questionnaire (standardized to a 0-to-100 scale) was higher in the RYGB group than in the best medical treatment group for several domains. The mean differences were 13.5 (95% CI, 5.5-21.6, P = 0.001) for general health, 19.7 (95% CI, 9.1-30.3, P < 0.001) for pain, 6.1 (95% CI, -4.8 to 17.0, P = 0.27) for social functioning, 8.3 (95% CI, 0.23 to 16.3, P = 0.04) for emotional well-being, 12.2 (95% CI, 3.9-20.4, P = 0.004) for vitality, 16.8 (95% CI, -0.75 to 34.4, P = 0.06) for mental health, 21.8 (95% CI, 4.8-38.7, P = 0.01) for physical health and 11.1 (95% CI, 2.24-19.9, P = 0.01) for physical functioning. Serious adverse events were experienced in 7/46 (15.2%) after best medical treatment and 11/46 patients (24%) after RYGB (P = 0.80). Interpretation: Albuminuria remission was not statistically different between best medical treatment and RYGB after 5 years in participants with diabetic kidney disease and class 1 obesity, with 6-7 in ten patients achieving remission of microalbuminuria (uACR <30 mg/g) in both groups. RYGB was superior in improving glycemia, diastolic blood pressure, lipids, body weight, and quality of life. Funding: The study was supported by research grants from Johnson & Johnson Brasil, Oswaldo Cruz German Hospital, and by grant 12/YI/B2480 from Science Foundation Ireland (Dr le Roux) and grant 2015-02733 from the Swedish Medical Research Council (Dr le Roux). Dr Pereira was funded by the Chevening Scholarship Programme (Foreign and Commonwealth Office, UK).

Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program.

OBJECTIVE: This analysis of 3,375 adults with overweight/obesity across the Semaglutide Treatment Effect in People with obesity (STEP) 1, 3, and 4 trials evaluated whether more participants with prediabetes had normoglycemia after 68 weeks' treatment with once-weekly semaglutide 2.4 mg plus lifestyle intervention versus placebo and assessed changes in glucose metabolism in participants with prediabetes. RESEARCH DESIGN AND METHODS: STEP 1, 3, and 4 were phase 3, 68-week, randomized, placebo-controlled, multinational trials; STEP 4 had a 20-week semaglutide run-in and 48-week randomized period. Analyses included changes (week 0-68; before the washout period) in glycemic status (prespecified: STEP 1 and 3; post hoc: STEP 4), and in HbA1c, fasting plasma glucose (FPG), and HOMA insulin resistance (HOMA-IR) among participants with prediabetes (post hoc). RESULTS: Significantly more participants with baseline (week 0) prediabetes (n = 1,536) had normoglycemia at week 68 with semaglutide versus placebo (STEP 1, 84.1% vs. 47.8%; STEP 3, 89.5% vs. 55.0%; STEP 4, 89.8% vs. 70.4%; all P < 0.0001). Fewer participants with baseline normoglycemia had prediabetes at week 68 with semaglutide versus placebo (STEP 1, 2.9% vs. 10.9%; STEP 3, 3.2% vs. 5.8%; STEP 4, 1.1% vs. 5.0%). Semaglutide resulted in greater improvements in HbA1c, FPG, and HOMA-IR than placebo among participants with baseline prediabetes (all P < 0.01). CONCLUSIONS: STEP 1, 3, and 4 collectively provide a robust assessment of the effects of semaglutide on glucose metabolism and prediabetes in a large cohort of adults with overweight/obesity while on treatment. Among participants with baseline prediabetes, 68 weeks' treatment with semaglutide versus placebo led to significant improvements in glucose metabolism and a higher likelihood of normoglycemia.

Dipeptidyl peptidase-4 activity, lipopolysaccharide, C-reactive protein, glucose metabolism, and gut peptides 3 months after bariatric surgery.

BACKGROUND: Bariatric surgery induces weight loss, but changes in glucose metabolism, gut peptides, and inflammatory biomarkers still have conflicting results. SETTINGS: University hospital. OBJECTIVES: We investigated glucose metabolism, gut hormones, and inflammatory profile after bariatric surgery and medical treatment. METHODS: Forty patients with obesity were recruited and were subjected to Roux-en-Y gastric bypass (n = 15; Bariatric Surgery Group - BSG) or received medical care (n = 20; MG). Sleeve gastrectomy was performed in five patients who were excluded from analysis. Glucose, insulin, homeostatic model for the assessment of insulin resistance (HOMA-IR), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), glucagon, ghrelin, dipeptidyl peptidase-4 (DPP-4) activity, circulating lipopolysaccharide (LPS), LPS-binding protein (LPB) and high-sensitivity C-reactive protein (hs-CRP) were evaluated before and three months after each treatment. Except for HOMA-IR, hs-CRP, and LBP, all variables were assessed at fasting and 30- and 60-minutes after a standard meal. RESULTS: After 3 months, both groups lost weight. However, BSG had a more extensive reduction than MG (respectively, 17.6% vs. 4.25%; P < 0.01). Except for LPS levels, higher on BSG than MG (1.38 ± 0.96 vs. 0.83 ± 0.60 EU/ml, P < 0.01), groups were similar before treatment. In respect to metabolic/hormonal changes, the BSG showed higher glucose, insulin, GLP-1, and GIP levels at 30-min and also GLP-1 at 30- and 60-minutes. DPP-4 activity, HOMA-IR, and fasting LBP did not change. LPS levels at 60-minutes decreased after surgery in the BSG. hs-CRP decreased on BSG compared to MG. CONCLUSIONS: Bariatric surgery resulted in more extensive effects on glucose metabolism, gut hormones, and inflammation.

Evaluation of Heart Rate Variability and Endothelial Function 3 Months After Bariatric Surgery.

We investigated endothelial and autonomic nervous functions after bariatric surgery. For this, we prospectively recruited 40 patients for bariatric surgery or medical treatment (20 in each group). Heart rate variability (HRV) and endothelial function were evaluated before and 3 months after treatments. Glucagon-like peptide 1 (GLP-1), insulin, and glucose at fasting and 30 and 60 min after a standard 300-kcal meal were also analyzed. Surgery but not medical care increased HRV in all time-domain variables, while frequency-domain variables, vascular elasticity, and endothelial reactivity did not change. Changes in GLP-1 and insulin resistance markers did not correlate with HRV. After 3 months, bariatric surgery improved the parasympathetic activity of cardiac autonomic function. Trial registration: NCT03911479.

Roux-En-Y Gastric Bypass in Type 2 Diabetes Patients with Mild Obesity: a Systematic Review and Meta-analysis.

This study aimed to evaluate the effectiveness of only Roux-en-Y gastric bypass (RYGB) in patients with type 2 diabetes (T2D) and body mass index (BMI) of 30-40 kg/m2. A literature search was performed on MEDLINE, Embase, and Cochrane CENTRAL. The searches were performed in February 2017. English was the target language of the publications. The PICO question was used to determine eligibility for studies to be included: population, patient with BMI 30-40 kg/m2; intervention, RYGB; comparison, control group with medical care alone; and outcome, metabolic outcomes. Only randomized clinical trials (RCT) were selected. The main outcome was T2D remission. Secondary outcomes were metabolic effect of RYGB, such as hypertension and dyslipidemia. A total of five RCTs were included. The studies included a larger proportion of women, and the average time of T2D duration ranged between 6 and 10 years with 43.3% of the patients having a BMI below 35 kg/m2. Despite randomization, the baseline demographics such as age, HbA1c, and duration of diabetes were often less favorable in the surgical group. At the longest follow-up, RYGB significantly improves total and partial type 2 remission, OR 17.48 (95% CI 4.28-71.35) and OR 20.71 (95% CI 5.16-83.12), respectively. HbA1c also reduces at longest follow-up in the surgery group (- 1.83 (95% CI - 2.14; - 1.51)). All these three outcomes revealed high level of evidence according to GRADE evaluation. There is already strong evidence that RYGB improves metabolic outcomes for at least 5 years in patients with class I obesity.

What is the impact on the healthcare system if access to bariatric surgery is delayed?

BACKGROUND: Bariatric surgery has been available as part of the Brazilian Public Health System for patients with body mass index>40 kg/m2 (or>35 kg/m2 with co-morbidities) since 1999. However, access to surgery is challenging, with eligible patients waiting up to 7 years before surgery. OBJECTIVE: Our objective was to compare costs and effectiveness of different waiting times before surgery versus prompt surgery. SETTINGS: Public practice. METHODS: A Markov microsimulation model compared 5 different strategies: no surgery, prompt surgery, and delaying surgery for 1, 2, 4, and 7 years. Markov tracker variables and states reflected changes in body mass index, type 2 diabetes status (including remission and relapse), and cardiovascular events. Time horizon was 20 years; discount rate, 5%; and the perspective of the Brazilian Public Health System. Effectiveness was calculated as quality adjusted life years. RESULTS: Prompt surgery was the least costly and most effective strategy compared with any delay. Costs increased and effectiveness diminished progressively with the length of delays. Waiting 7 years for surgery was the most expensive and least effective strategy. Prompt surgery maintained dominance in 99.9%, 90.7%, 96.1%, and 94.2% of simulations in probabilistic sensitivity analyses versus 1-, 2-, 4-, and 7-year delays, respectively. Immediate surgery was very cost effective compared with no surgery in the case base. In the scenario with all patients having type 2 diabetes, immediate surgery was dominant to any strategy, including the no surgery group. CONCLUSIONS: Delaying bariatric operations is more expensive and less effective compared with prompt surgery and very cost effective compared with no surgery. Public health systems should pursue strategies to accelerate access to surgery to decrease obesity related complications and mortality of patients, but also to improve cost effectiveness.

Microvascular Outcomes after Metabolic Surgery (MOMS) in patients with type 2 diabetes mellitus and class I obesity: rationale and design for a randomised controlled trial.

INTRODUCTION: There are several randomised controlled trials (RCTs) that have already shown that metabolic/bariatric surgery achieves short-term and long-term glycaemic control while there are no level 1A of evidence data regarding the effects of surgery on the microvascular complications of type 2 diabetes mellitus (T2DM). PURPOSE: The aim of this trial is to investigate the long-term efficacy and safety of the Roux-en-Y gastric bypass (RYGB) plus the best medical treatment (BMT) versus the BMT alone to improve microvascular outcomes in patients with T2DM with a body mass index (BMI) of 30-34.9 kg/m2. METHODS AND ANALYSIS: This study design includes a unicentric randomised unblinded controlled trial. 100 patients (BMI from 30 to 34.9 kg/m2) will be randomly allocated to receive either RYGB plus BMT or BMT alone. The primary outcome is the change in the urine albumin-to-creatinine ratio (uACR) captured as the proportion of patients who achieved nephropathy remission (uACR<30 mg/g of albumin/mg of creatinine) in an isolated urine sample over 12, 24 and 60 months. ETHICS AND DISSEMINATION: The study was approved by the local Institutional Review Board. This study represents the first RCT comparing RYGB plus BMT versus BMT alone for patients with T2DM with a BMI below 35 kg/m2. TRIAL REGISTRATION NUMBER: NCT01821508; Pre-results.

The Diabetes Surgery Summit II Guidelines: a Disease-Based Clinical Recommendation.

There is mounting evidence, derived from mechanistic studies, RCTs, and other high-quality studies that there are weight loss independent antidiabetic effects of gastrointestinal surgery. Additionally, there appears to be no relation between the positive metabolic outcomes to baseline BMI. The outdated US National Health Institutes guidelines from 1991 were centered on BMI only criterion and often misleading. The Second Diabetes Surgery Summit held in collaboration with leading diabetes organizations and endorsed by a large group of international Professional Societies developed guidelines that defined eligibility based on the severity and degree of T2D medical control while referring to obesity as a qualifier and not the sole criterion. That is the first time that guidelines are provided to put metabolic surgery into the T2D treatment algorithms.