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Ten-year RCT outcomes demonstrate metabolic surgery more effective than medical therapy in the long-term control of T2DM

Fri, 01/22/2021 - 07:29
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The first ever outcomes from ten years of follow-up from a randomised controlled trial assessing metabolic surgery vs. conventional medical therapy, has concluded that surgery is more effective than conventional medical therapy in the long-term control of T2DM. The findings were reported in the paper, ‘Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial’, published in The Lancet.

The study also shows that 37.5% of surgically-treated patients remained diabetes-free throughout the ten-year period of the trial. This demonstrates, in the context of the most rigorous type of clinical investigation, that a “cure” for type 2 diabetes can be achieved, according to researchers from King’s College London and the Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. In 2009, American Diabetes Association defined “cure” of diabetes as a continued state of disease remission for more than five years.

Francesco Rubino
Francesco Rubino
 

“The findings from this study provide the most robust scientific evidence yet that full-blown type 2 diabetes is a curable disease, not inevitably progressive and irreversible,” said Professor Francesco Rubino, senior author of the report and Chair of Bariatric and Metabolic Surgery at King’s College London and a consultant surgeon at King’s College Hospital in London. “In addition to representing a major advance in the treatment of diabetes, metabolic surgery is our best lead to the elusive cause of the disease.”

Compared to conventional medical treatment, surgery also resulted in better overall metabolic control, lower cardiovascular risk, better kidney function and quality of life. Notably, patients treated surgically had a significant lower incidence of diabetes-related complications, including cardiac, renal, and neurological adverse events. Metabolic surgery also reduced medication usage, including drugs for diabetes, high blood pressure and dyslipidaemia.

“These data corroborate the notion that surgery can be a cost-effective approach to treating type 2 diabetes,” added Professor Geltrude Mingrone, first author of the report, Professor of Medicine at the Catholic University of Rome and a Professor of Diabetes and Nutrition at King’s College London.  “ The evidence is now more than compelling that metabolic surgery should be considered as a main therapeutic option for the treatment of patients with severe type 2 diabetes and obesity.”

In this study, the authors reported the ten-year outcomes from a randomised controlled trial that compared metabolic surgery by Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) with medical therapy plus lifestyle interventions for the treatment of advanced type 2 diabetes. The two-year (Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med 2012; 366: 1577–85) and five-year outcomes (Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single centre, randomised controlled trial. Lancet 2015; 386: 964–73) of the study were previously reported and the authors continued to follow up patients for evaluation of durability of diabetes remission and secondary endpoints.             

The study

For the study, 60 were randomly assigned to the conventional medical therapy (n=20), RYGB (n=20) or BPD (n=20) groups between April 2009 and October 2011. In total, 57 patients (95%) completed the ten-year follow-up. The outcomes for the medically treated patients who died (one patient) and crossed over to surgery (two patients) were not included in the per-protocol analysis (n=15 medical therapy, n=20 RYGB, n=20 BPD), but were included in the intention-to-treat analysis for diabetes remission (n=18 medical therapy, n=20 BPD, and n=20 RYGB).

At ten tears, no patients in the medical therapy group were in diabetes remission vs. 15 (37.5%) patients in both surgically groups (per-protocol analysis, ten patients after BPD (50%) and five after RYGB (25%; p=0·19) who maintained diabetes remission throughout the ten-year period of the study.

In the intention-to-treat analysis, ten-year remission rates were 5.5% for medical therapy (one patient went into remission after crossover to surgery), 50% for BPD and 25% for RYGB (p=0.0082). Relative risks were 9·0 (95% CI 1·3–63·5) for BPD versus medical therapy and 4·5 (0·58–35·0) for Interestingly, none of the patients who did not go into remission in the first two years after surgery went into remission thereafter. For those patients who did go into remission at two years, 20 (58.8%) had a relapse of hyperglycaemia during follow-up (ten (52.6%) of 19 in the BPD group and ten (66.7%) of 15 in the RYGB group).

The median diabetes-free survival time was five years for RYGB and nine years in BPD; the log-rank test (p=0·25) indicated no difference between the two surgical groups. The cumulative risk of relapse during the ten-year follow-up study, showed that the highest risk of relapse occurred within the first five years after surgery.

Diabetes-related complications

Furthermore, medically treated patients had a significantly higher incidence of diabetes-related complications than surgically treated patients (72.2% vs 5%). Participants in the medical therapy group had both macrovascular (two myocardial infarctions, one fatal) and microvascular diabetic complications (retinopathy [n=2], nephropathy [n=5], and neuropathy [n=4]). Only two patients among surgically treated patients developed diabetic complications (one case of macro-albuminuria in each surgical group).

More patients in the medical therapy group required insulin therapy compared with the surgical group (53.3% vs 2.5%) and significantly more cardiovascular medications (lipid-lowering and blood pressure-lowering medications) than patients in both surgical groups (p<0·0001). The use of medications increased over time in the medical therapy group.

“Given the fact that, by design, all patients at baseline had inadequately controlled, long-standing diabetes and many were insulin requiring, I think it is quite remarkable and clear evidence that T2DM is “curable” even when not mild or early onset only,” explained Professor Rubino. “Despite the evidence that surgery can rapidly and dramatically improve diabetes, less than 1% of surgical candidates have access to metabolic surgery in most countries. Diabetes is one of the leading causes of mortality and morbidity in Western societies and significantly increases the risk of severe COVID-19 and mortality from the virus. Furthermore, metabolic surgery operations have been suspended for even longer than other elective surgical procedures during the current pandemic. Metabolic surgery is arguably the most effective available therapy for type 2 diabetes and can be a life-saving option for many patients. It should be appropriately prioritised in times of pandemic and beyond.”

Additional ten-year outcomes from the RCT included:

  • Surgery resulted in significantly lower bodyweight, BMI and waist circumference than medical therapy.
  • Weight regain was 7.1% among patients who maintained remission versus 8.2% for those who had a diabetes relapse, however weight changes did not predict diabetes remission or relapse among patients who underwent surgery.
  • Both surgical procedures were associated with significant lower HOMA-IR scores than medical therapy, indicating better insulin sensitivity.
  • Patients in the medical therapy group had significantly higher cardiovascular risk than surgically treated patients
  • There were no differences in blood pressure among groups but patients in the medical therapy group required more anti-hypertensive medications than patients who underwent surgery; and
  • Patients who underwent surgery had better QOL than patients treated medically.

“Our findings suggest that it might be possible to reduce the frequency of glycaemic monitoring in patients who maintain at least five years of remission of type 2 diabetes although larger studies are needed to confirm this finding,” the paper concluded. “Clinicians and policy makers should ensure that metabolic surgery is appropriately considered in the management of patients with obesity and type 2 diabetes.”

This study is registered with ClinicalTrials.gov, NCT00888836.