Comparative effectiveness of bariatric surgeries in patients with obesity and type 2 diabetes mellitus: A network meta‐analysis of randomized controlled trials

Summary A network meta‐analysis of randomized controlled trials (RCTs) was performed to determine the hierarchies of different bariatric surgeries in patients with obesity and type 2 diabetes mellitus (T2DM), in terms of diabetes remission and cardiometabolic outcomes. Seventeen RCTs and six bariatric surgeries, including single anastomosis (mini) gastric bypass (mini‐GBP), biliopancreatic diversion without duodenal switch (BPD), laparoscopic‐adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG), Roux‐en‐Y gastric bypass (RYGBP), greater curvature plication (GCP) and nonsurgical treatments (NST) were included. Mini‐GBP, BPD, LSG, RYGBP and LAGB (from best to worst), as compared with NST, were all significantly associated with the remission of T2DM. For the follow‐up period > 3 years, BPD, mini‐GBP, RYGBP and LSG (from best to worst) were significantly superior to NST in achieving the remission of T2DM. For secondary outcomes, the overall ranking for bariatric surgeries was RYGBP > BPD > LSG > LAGB after comprehensively weighting glucose, weight, systolic and diastolic pressure, total cholesterol, triglycerides, high‐density lipoprotein cholesterol (HDL‐C) and low‐density lipoprotein cholesterol (LDL‐C). Mini‐GBP has the greatest probability of achieving diabetes remission in adults with obesity and T2DM, yet BPD was the most effective in long‐term diabetes remission. RYGBP appears to be the most favourable alternative treatment to manage patients with cardiometabolic conditions.


Summary
A network meta-analysis of randomized controlled trials (RCTs) was performed to determine the hierarchies of different bariatric surgeries in patients with obesity and type 2 diabetes mellitus (T2DM), in terms of diabetes remission and cardiometabolic outcomes. Seventeen RCTs and six bariatric surgeries, including single anastomosis (mini) gastric bypass (mini-GBP), biliopancreatic diversion without duodenal switch (BPD), laparoscopic-adjustable gastric banding (LAGB), laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGBP), greater curvature plication (GCP) and nonsurgical treatments (NST) were included. Mini-GBP, BPD, LSG, RYGBP and LAGB (from best to worst), as compared with NST, were all significantly associated with the remission of T2DM. For the follow-up period > 3 years, BPD, mini-GBP, RYGBP and LSG (from best to worst) were significantly superior to NST in achieving the remission of T2DM. For secondary outcomes, the overall ranking for bariatric surgeries was RYGBP > BPD > LSG > LAGB after comprehensively weighting glucose, weight, systolic and diastolic pressure, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Mini-GBP has the greatest probability of achieving diabetes remission in adults with obesity and T2DM, yet BPD was the most effective in long-term diabetes remission. RYGBP appears to be the most favourable alternative treatment to manage patients with cardiometabolic conditions.

K E Y W O R D S
bariatric surgeries, diabetes remission, cardiometabolic outcome, network meta-analysis 1 | INTRODUCTION Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance caused by pancreatic β-cell dysfunction. 1 From 1980 to 2004, the incidence and prevalence of T2DM nearly quadrupled owing to the global rise in obesity, sedentary lifestyles and population aging. 2 As the eighth leading cause of disability in 2016, diabetes substantially contributes to the socio-economic pressures of individuals and the overwhelming health care costs. 3 More than 60% of patients with T2DM have a body mass index (BMI) ≥ 30 kg/m 2 , and patients with obesity are more likely to develop T2DM. 4 Whole-genome analysis of gene expression products (i.e. mRNAs) has uncovered several genetic associations between T2DM and obesity by correlating genotypes with phenotypes. 5 Sustained weight loss is a highly effective strategy to treat and prevent T2DM, with low-calorie diets 6 and bariatric surgeries 7 being the ideal treatments to achieve T2DM remission.
The primary purpose of bariatric surgery is to achieve and sustain significant weight loss, which leads to the improvement and remission of many obesity-related comorbidities, especially T2DM. [8][9][10] Considerable evidence has suggested that T2DM can be controlled by bariatric surgery in patients with morbid obesity. [11][12][13][14] In addition to weight loss, bariatric surgery provides additional health benefits, including improvements in cardiometabolic comorbidities like dyslipidaemia, hypertension and obstructive sleep apnoea. 15  Checklist and Explanations. 18 The study protocol was prespecified and registered on the International Prospective Register of Systematic Reviews (PROSPERO) under the code CRD42018110775. 19 A literature search was conducted on Medline through PubMed, Embase and Web of Knowledge in July 2019. The references of articles identified through the initial screening were used to identify articles missed by the computerized database search. The following search terms were used: bariatric surgery, bariatric operation, bariatric procedure, obesity surgery, metabolic surgery, stomach stapling, biliopancreatic bypass, biliopancreatic diversion, duodenal switch, sleeve gastrectomy and gastric bypass. These terms were combined using the set operator "AND" with type 2 diabetes mellitus, non-insulin-dependent diabetes (NIDDM) and T2DM.

| Patient and public involvement
There was no patient and public involvement as this was a network meta-analysis.

| DISCUSSION
Patients with morbid obesity and T2DM continue to be a major public health burden worldwide, despite some advances in its diagnosis and treatment. 15 Recently, the prevention and treatment of diabesity-the combination of obesity and T2DM-has become an important task for physicians globally. 40,41 While sustained weight loss is highly effective in preventing and treating T2DM, it is a challenging therapeutic option for most patients. In this study, we performed a network metaanalysis of RCTs published to date to determine the most effective bariatric surgery for patients with obesity and T2DM and obesityrelated comorbid conditions.
Our findings revealed that mini-GBP is most likely to achieve diabetes remission. Previously, mini-GBP was found to be an easier, safer, faster and more effective metabolic operation when compared with RYGB, which is the gold standard of bariatric surgeries. 42,43 Mini-GBP is a new bypass procedure with a shorter operation time than RYGB and LSG, involving a single anastomosis between a long, narrow gastric pouch and an omega jejunal loop. 44,45 A landmark YOMEGA study revealed that mini-GBP is not inferior to RYGBP on weight loss and metabolic improvement for patients with morbid obesity. 46 Numerous studies have shown that mini-GBP is a short and straightforward procedure leading to excellent outcomes and fewer complications, such as intestine obstruction or internal herniation, both of which are commonly associated with bariatric surgery. [47][48][49] An increasing number of surgeons have adopted mini-GBP, which has gradually become accepted as the mainstream bariatric procedure. 50 The mechanism of glycaemic control after mini-GBP is similar to that after RYGBP, which includes an immediate post-operative reduction in caloric intake, durable weight loss and duodenal bypass. [51][52][53] Mini-GBP clearly combines 'simplicity' and 'reversibility,' two criteria of metabolic procedures proposed by the International Diabetes Federation for T2DM treatment. 54 While SG is irreversible, RYGB is technically more challenging to perform and reverse.
Our results suggest that RYGBP is the most favourable alternative surgery to manage cardiometabolic outcomes in most patients with T2DM. RYGBP could induce weight loss with similar magnitude between adolescents and adults but higher rate of remission of diabetes and hypertension in adolescents and adults. 55 The lipid and glucose profiles were substantially improved after RYGBP, including decreased total cholesterol, LDL-C, triglycerides, insulin resistance (assessed by homeostasis model assessment for insulin resistance) and increased HDL-C. 56 In addition, RYGBP leads to significant improvements in brachial artery diameter, endothelial-independent vasodilation and the Framingham cardiovascular risk score 57 and offer some of the best long-term cardiovascular benefits, especially among patients with previous risk factors. 58 Glycated haemoglobin (HbA1c) improved more in the mini-GBP group than in the RYGBP group for patients with type 2 diabetes, and the incidence of steatorrhea was higher in the mini-GBP group than in the RYGBP group for the perprotocol population. 46  Note: Comparisons between drugs should be read from left to right. The estimates are located at the crossing between the column-defining treatment and row-defining treatment. For mean change of glucose, weight loss, systolic and diastolic pressure, total cholesterol, triglycerides and LDL-C. An SMD lower than 0.01 favours the column-defining treatment; for mean change of HDL-C, an SMD greater than 0.01 favours the column-defining treatment. The significant results are presented in bold. Abbreviations: BPD, biliopancreatic diversion without duodenal switch; CrI, credible interval; LAGB, laparoscopic-adjustable gastric banding; LDL-C, low-density lipoprotein cholesterol; LSG, laparoscopic sleeve gastrectomy; HDL-C, high-density lipoprotein cholesterol; NST, nonsurgical treatment; RYGBP, Roux-en-Y gastric bypass; SMD, standardized mean difference. studies with more than 3-year follow-up periods, which were consistent with the overall analysis.

| CONCLUSION
In summary, mini-GBP is more likely to achieve diabetes remission when compared with other bariatric surgeries, but BPD appears to be the most effective surgery for achieving long-term diabetes remission.
RYGBP is the most favourable alternative to manage cardiometabolic conditions. The effects of mini-GBP on cardiometabolic outcomes were inconclusive and require future studies.