Gastric bypass surgery vs intensive lifestyle and medical intervention for type 2 diabetes: the CROSSROADS randomised controlled trial

Abstract

Aims/hypothesis Mounting evidence indicates that Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes, but randomised trials comparing surgical vs nonsurgical care are needed. With a parallel-group randomised controlled trial (RCT), we compared RYGB vs an intensive lifestyle and medical intervention (ILMI) for type 2 diabetes, including among patients with a BMI <35 kg/m2. Methods By use of a shared decision-making recruitment strategy targeting the entire at-risk population within an integrated community healthcare system, we screened 1,808 adults meeting inclusion criteria (age 25–64, with type 2 diabetes and a BMI 30–45 kg/m2). Of these, 43 were allocated via concealed, computer-generated random assignment in a 1:1 ratio to RYGB or ILMI. The latter involved ≥45 min of aerobic exercise 5 days per week, a dietitian-directed weight- and glucose-lowering diet, and optimal diabetes medical treatment for 1 year. Although treatment allocation could not be blinded, outcomes were determined by a blinded adjudicator. The primary outcome was diabetes remission at 1 year (HbA1c <6.0% [<42.1 mmol/mol], off all diabetes medicines). Results Twenty-three volunteers were assigned to RYGB and 20 to ILMI. Of these, 11 withdrew before receiving any intervention. Hence 15 in the RYGB group and 17 in the IMLI group were analysed throughout 1 year. The groups were equivalent regarding all baseline characteristics, except that the RYGB cohort had a longer diabetes duration (11.4±4.8 vs 6.8±5.2 years, p=0.009). Weight loss at 1 year was 25.8±14.5% vs 6.4±5.8% after RYGB vs ILMI, respectively (p<0.001). The ILMI exercise programme yielded a 22±11% increase in V̇O2max (p <0.0001), whereas V̇O2max after RYGB was unchanged. Diabetes remission at 1 year was 60.0% with RYGB vs 5.9% with ILMI (p=0.002). The HbA1c decline over 1 year was only modestly more after RYGB than ILMI: from 7.7±1.0% (60.7 mmol/mol) to 6.4 ±1.6% (46.4 mmol/mol) vs 7.3±0.9% (56.3 mmol/mol) to 6.9±1.3% (51.9 mmol/mol), respectively (p=0.04); however, this drop occurred with significantly fewer or no diabetes medications after RYGB. No life-threatening complications occurred. Conclusions/interpretation Compared with the most rigorous ILMI yet tested against surgery in a randomised trial, RYGB yielded greater type 2 diabetes remission in mild-to-moderately obese patients recruited from a well-informed, population-based sample. Trial registration ClinicalTrials.gov NCT01295229

Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations

“…The GI tract is an important contributor to normal glucose homeostasis (35), and mounting evidence, especially over the past decade, has demonstrated benefits of bariatric/metabolic surgery to treat and prevent T2D (3,5,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(51)(52)(53). Beyond inducing weight loss-related metabolic improvements, some operations engage mechanisms that improve glucose homeostasis independent of weight loss (6), such as changes in gut hormones, bile acid metabolism, microbiota, intestinal glucose metabolism, and nutrient sensing (5,6,(26)(27)(28)(29)(30)(31)(32)(33)(34).…”

“…2A). Numerous RCTs with postoperative follow-up ranging between 1 and 5 years have consistently documented sustained diabetes remission in 30-63% of patients (LoE IB) (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Available data suggest an erosion of diabetes remission over time: 35-50% or more of patients who initially achieve remission of diabetes eventually experience recurrence.…”

“…Since DSS-I, a substantial body of additional evidence has accumulated, including from numerous randomized clinical trials (RCTs), demonstrating that bariatric/ metabolic surgery achieves superior glycemic control and reduction of cardiovascular risk factors in obese patients with T2D compared with various medical/lifestyle interventions (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Further research on mechanisms of action of these procedures (5,6,(26)(27)(28)(29)(30)(31)(32)(33)(34) has corroborated evidence in animal studies demonstrating an important role for the GI tract in glucose homeostasis (35), providing a biological rationale for the use of GI-based interventions to treat T2D.…”

Recent advancements in bariatric/metabolic surgery

“…This study compared LSG to gastric bypass (LSAGB) for the treatment of T2DM in Asian patients with BMI <35 kg/m 2 and was the first study to prove that gastric bypass (a duodenum exclusion procedure) had better efficacy on T2DM remission than LSG (non‐duodenum exclusion procedure). Following this landmark study, many RCT focusing on the comparison of metabolic surgery and medical treatment for the treatment of T2DM have been carried out and universally showed that metabolic surgery is more effective than medical treatment in glycemic control 91, 92, 93, 94, 95, 96, 97, 98, 99. Table 2 lists the results of RCT trials on surgical treatment versus medical treatment for T2DM.…”

Diabetes remission off medications is not a suitable endpoint for comparing bariatric/metabolic surgery with pharmacotherapy

“…To the Editor: In their publication in Diabetologia, Cummings et al [1] describe how they used a randomised trial to compare the best available intensive lifestyle and medical intervention (ILMI) against Roux-en-Y gastric bypass (RYGB), and concluded that surgery achieved greater type 2 diabetes remission in mildly to moderately obese patients. However, mean HbA 1c values were not statistically different between groups at the end of study, which was not explicitly stated in the abstract.…”