Durable Diabetes Remission Likelier With Earlier Surgery

Miriam E. Tucker

December 16, 2020

New results from an observational study are the latest to show that bariatric surgery performed soon after diagnosis of type 2 diabetes in patients with obesity is more likely to result in long-lasting remission.

Seven-year data for over 800 patients at 10 US hospitals participating in the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study were published online in the Journal of Clinical Endocrinology & Metabolism.

The report extends the group's previous findings by 4 years, so that at 7 years diabetes remission was still more likely among those who underwent Roux-en-Y gastric bypass (RYGB) than laparoscopic gastric banding (LAGB) even after adjustment for weight loss.

This suggests that the mechanism for improved beta-cell function after RYGB extends beyond weight loss alone, say the authors, led by bariatric surgeon Jonathan Q. Purnell, MD, professor of medicine at Oregon Health & Science University, Portland.   

"A prevalent notion...is that surgery is something you should reserve until you have failed medical management. In that situation, you're stacking the odds against the patient in terms of their getting the full benefit," Purnell told Medscape Medical News in an interview.

At least 10 previous randomized clinical trials have shown the superiority of weight loss surgery over medical approaches for type 2 diabetes remission, Purnell said.

"What our data and other studies really reinforce is the fact that in the natural progression of the disease [there is] an ongoing decline in islet cell secretory capacity. If bariatric surgery is positioned earlier it gives you a greater benefit for preserving that secretory capacity. Don't wait till they've failed metformin and [other medications]."

But typically in the United States, insurance companies mandate a trial of a medical weight loss program before covering bariatric surgery.

"That's hamstringing patients and clinicians into something that should be a judgment call at the time they're seen...The idea that patients need to lose 5% to 10% of their weight prior to surgery is not rooted in science," Purnell asserted.

Not Everyone With Obesity and Diabetes Needs Early Surgery

Asked to comment, endocrinologist Jeffrey I. Mechanick, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai Hospital, New York City, told Medscape Medical News that the study's conclusion about having surgery sooner "isn't wrong but we need to make sure it's not generalized to the broader statement that all patients with diabetes and obesity should be considered for bariatric surgery early."

"There are all different kinds of people with all different kinds of risk categories and ethnicities and pathophysiologies. The fact is the majority of people do respond in some fashion to lifestyle and to drugs."

Mechanick pointed to 2017 guidance issued by several professional medical and surgical societies that metabolic surgery "should be recommended" to treat type 2 diabetes in certain patient groups, including those with BMI 40 kg/m2 and above, or with BMI 35-39.9 kg/m2 "when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy," as well as down to BMI 30.0-34.9 kg/m2, "if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications."

According to Mechanick, who was a coauthor on that guidance, "We said that bariatric surgery has a very defined evidence-based place in the comprehensive management of obesity and diabetes in the more severe cases…In the real world I'm not going to recommend bariatric surgery for someone who is low risk."

However, he added, "We do need better evidence-based guidance on when you start the conversation about bariatric surgery specifically."

Diabetes Remission at 7 Years More Likely With RYGB

In their article, Purnell and colleagues note that LABS-2 was an observational, nonrandomized study of 2256 adults who underwent RYGB or LAGB between 2006 and 2009, of whom 37% (827) had type 2 diabetes.

Following surgery, 68% of those with diabetes achieved partial or complete remission, defined as A1c levels of 5.7%-6.5% (39-48 mmol/M) and < 5.7% (39 mmol/M), respectively, without use of glucose-lowering medications at one or more timepoints after surgery. The decision to continue or stop medications was made by the individual patient and clinician.

Among those with diabetes, 78% opted for RYGB and 22% for LAGB. Despite the nonrandomization, most relevant baseline characteristics between the two groups were similar.

At baseline, those who achieved complete or partial diabetes remission were on average younger at the time of surgery (48 vs 52 years; P = .0002), had a lower percent body fat (P = .0012), had shorter diabetes duration (6 vs 13.5 years; P < .0001), had a lower A1c (7.7% vs 6.8%; P < .0001), and were less likely to be taking insulin (66% vs 24%; P < .0001).

They had similar levels of insulin resistance but higher levels of C-peptide, proinsulin, and beta-cell secretory function.

The proportions in complete or partial diabetes remission peaked 2 to 3 years after both procedures — 62% with RYGB and 29% with LAGB — and then declined through the rest of the 7-year follow-up to 57% and 22.5%, respectively, by year 7.  

After adjustment for baseline differences, individuals in both surgery groups were more likely to achieve diabetes remission during follow-up if they had lower baseline insulin levels, higher C-peptide levels, and higher beta-cell function.

And with adjustment for greater weight loss in the RYGB group (which the authors had previously reported), the probability of diabetes remission was also greater for RYGB than LAGB at all timepoints, increasing from an adjusted relative risk of 1.86 in the first year after surgery to 3.96 after 7 years.   

Sleeve Gastrectomy Now Most Common Bariatric Procedure

In the years since the study began, LAGB has fallen out of favor and sleeve gastrectomy has become the most common bariatric procedure, with RYGB now used in about a third of patients.

Although sleeve gastrectomy and RYGB performed similarly in the STAMPEDE study, "those patients had already failed medical management. They had higher A1cs, longer diabetes duration, and were more likely on insulin, [and in] an advanced state of diabetes less likely to see improvement," Purnell said.

"Most people now get the sleeve. I think it would be comparable to what we saw with gastric bypass, although the data aren't quite as good," he added.

Mechanick said, "More studies are going to need to be done with bariatric surgery and also nonsurgical bariatric procedures, and also, in my view, not just alone but in combination with pharmacotherapy and lifestyle."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Purnell has reported consulting for Novo Nordisk. Mechanick has reported receiving honoraria for lectures and program development from Abbott Nutrition.

J Clin Endocrinol Metab. Published online December 3, 2020. Abstract

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