American Diabetes Association 76th Scientific Sessions:

Substantial Evidence Supports Metabolic Surgery for Patients with Type 2 Diabetes

Philip R. Schauer, MD presented, "What Is the Evidence in Support of Metabolic Surgery for the Treatment of Type 2 Diabetes?" at the 76th Scientific Sessions of the American Diabetes Association, June 10–14, 2016 in New Orleans. Dr. Shauer is Professor of Surgery at the Cleveland Clinic Lerner College of Medicine and Director of the Bariatric and Metabolic Institute.

bariatric surgery, Roux-en-Y gastric bypass
Dr. Schauer began by outlining his presentation:

  • Rationale for metabolic surgery
  • American Diabetes Association 2016 guidelines on surgery
  • Diabetes Surgery Summit and guidelines
  • Observational data of clinical outcomes on efficacy and adverse events
  • Clinical outcomes in 11 randomized clinical trials
  • Outcomes for patients with body mass index < and ≥35 kg/m2
  • Potential mechanisms of type 2 diabetes remission after surgery
  • Gaps in evidence supporting metabolic surgery
  • Key recommendations of Diabetes Surgery Summit guidelines

Rationale for Metabolic Surgery
National Health and Nutrition Examination Survey (NHANES) data from 2007–2010, which covered 4926 patients with type 2 diabetes, reported the following success rates of lifestyle plus drug therapy:
success rates of lifestyle plus drug therapyDr. Schauer asserted that the low success rate of patients achieving all three goals could be improved with metabolic surgery.

American Diabetes Association (ADA) Guidelines for Surgery
Dr. Schauer stressed that the ADA guidelines have not changed since 2009. The guidelines include:

  • Bariatric surgery may be considered for type 2 diabetic patients whose body mass index is over 35 kg/m2
  • Patients need lifelong monitoring
  • The surgery is not indicated in type 2 diabetic patients whose body mass index is 30–35 kg/m2

The June 2016 issue of Diabetes Care, contains an article by Cefalu, Rubino, and Cummings, entitled, "Metabolic Surgery for Type 2 Diabetes: Changing the Landscape of Diabetes Care."1 The article contains a joint statement by international diabetes organizations on metabolic surgery in the treatment algorithm for type 2 diabetes. The joint statement, in summary, is:

  • Though additional studies are needed to further demonstrate long-term benefits, sufficient clinical and mechanistic evidence supports inclusion of metabolic surgery among antidiabetes interventions for people with type 2 diabetes and obesity.

Observational Data on Clinical Outcomes of Metabolic Surgery in Patients with Type 2 Diabetes
Dr. Schauer cited a 2012 retrospective review of bariatric surgery and cardiovascular outcomes authored by Vest et al and published in Heart.2 The review covered 73 studies, including three randomized clinical trials.
Percent of patients whose condition was resolved or improvedLong-Term Changes in Hemoglobin A1C with Metabolic Surgery
In 2013, Brethauer et al3 compared changes in hemoglobin A1C after 6 years and longer with laparoscopic gastric band (n=32), laparoscopic sleeve gastrectomy n=23), and Roux- en-Y gastric bypass (n=162).

Percent reduction in hemoglobin A1C after 6+ years
Dr. Schauer then referred to the 2007 study by Sjöstrom,4 the longest-term study of mortality reduction in patients who have undergone bariatric surgery vs nonoperated controls. After 14 years, mortality had been reduced by 31%.

Risks of Metabolic Surgery in Patients with Type 2 Diabetes
Dr. Schauer cited a 2014 comparison of composite complication rates for surgeries undergone by patients with type 2 diabetes.5 Of 16,509 patients who underwent laparoscopic Roux-en-Y gastric bypass, 3.4% experienced a complication. Laparoscopic Roux-en-Y gastric bypass incurred the lowest complication rate of any of the eight surgical procedures evaluated. Only knee arthroplasty and laparoscopic hysterectomy carried a lower mortality rate than laparoscopic Roux-en-Y gastric bypass.

Postoperative composite complication rate (%) in patients with type 2 diabetes
In the June 2016 issue of Diabetes Care,1 Dr. Schauer and colleagues stressed that the three main complications of metabolic surgery are:

  • Severe hypoglycemia, <1%, which is usually controlled with diet or drug therapy
  • Increased suicide risk (rate not known)
  • Regain of some or all weight in 10–15% of patients

These complications must be weighed against the unimpressive results with insulin in terms of hemoglobin A1C, hypoglycemia, and weight gain (see the first table in this article).

Dr. Schauer enumerated the complications of diabetes drugs:

  • Hypoglycemia: pramlintide, insulin, sulfonylureas
  • Gastrointestinal symptoms: acarbose, metformin, bromocriptine, glucagon-like peptide 1 agonists
  • Renal insufficiency: metformin, glucagon-like peptide 1 agonists, insulin, sulfonylurea
  • Liver disease: metformin, sulfonylureas, thiazolidinediones
  • Heart failure: metformin, thiazolidinediones
  • Weight gain: insulin, sulfonylureas, thiazolidinediones
  • Fractures: thiazolidinediones
  • Drug-drug interactions: sulfonylureas
  • Genital mycotic infections: sodium-glucose transporter 2 inhibitors        

Randomized Clinical Comparisons of Metabolic Surgery vs Medical Therapy for Type 2 Diabetes
Dr. Schauer summarized 11 trials from 2008–2015 with follow-up ranging from 6–60 months. All but one resulted in statistically significant remission or change in hemoglobin A1C. He added a new prospective, randomized, parallel-group, single-center controlled trial, the COmparison of Surgery vs Medicine for Indian Diabetes (COSMID), which was presented at the 76th Scientific Sessions of the American Diabetes Association, June 10–14, 2016.

COSMID compared Roux-en Y gastric bypass (plus medical therapy as needed) with optimal medical and lifestyle management among Asian Indian adults with type 2 diabetes and body mass index 25-40 kg/m2. The 2-year study followed 80 subjects and found gastric bypass to be superior to medical management alone in treating patients with type 2 diabetes. COSMID was the first study to specifically address the Asian Indian population, whose pathogenesis of type 2 diabetes differs from that of Caucasians.

Five-Year Results of Surgical Treatment And Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE)
Dr. Schauer presented these results in April 2016 at the Scientific Session of the American College of Cardiology. STAMPEDE compared medical therapy, sleeve gastrectomy, and gastric bypass. The primary endpoint was change in hemoglobin A1C.

Percentage of patients who achieved hemoglobin A1C ≤6% (primary endpoint) The secondary endpoint was change in body mass index over 5 years. Reduction in body mass index was significant at P<.001 for both gastric bypass and sleeve gastrectomy vs medical therapy. The percent change in albumin/creatinine ratio was significant at P<.001.

Percent change in albumin/creatinine ratioNo significant changes were observed in macular edema or visual acuity with any of the three interventions. Retinopathy, however, was reduced by 8% with medical therapy, 17% with gastric bypass, and 14% with sleeve gastrectomy.

Randomized Clinical Trials of Surgery vs Medical Therapy for Type 2 Diabetes
Dr. Schauer summarized the outcomes of randomized clinical trials comparing surgical and medical therapy in patients with type 2 diabetes:

  • 11 studies, 794 randomized patients, 1–5 years of follow-up
  • Surgery was superior to medical therapy (P<.05) in all but one trial. Evaluated parameters were weight loss, hemoglobin A1C, type 2 diabetes remission, triglycerides, high-density lipoprotein cholesterol, remission of metabolic syndrome, quality of life, and reduction in medications
  • Most trials showed no difference in blood pressure or low-density-lipoprotein cholesterol
  • No perioperative complications occurred (<30 days), nor cardiovascular deaths. The most common surgical complication was anemia (15%). Eight percent (8%) of patients received a second operation. Five percent (5%) of patients experienced gastrointestinal complications. Hypoglycemia occurrence did not differ from controls.

Metabolic Surgery in Patients with Type 2 Diabetes with Body Mass Index Under vs Over 35 kg/m2
Dr. Schauer cited a meta-analysis by Cummings and Cohen published in 2016 in Diabetes Care.6 Seventy-two percent of patients with body mass index <35 kg/m2 in 33 trials experienced diabetes remission. Seventy-one percent (71%) of those with body mass index ≥35 kg/m2 in 94 trials covering 94,579 patients experienced diabetes remission.

Agency for Healthcare Research and Quality (AHRQ) Systematic Review, 2013
Dr. Schauer cited this 100-page detailed comparison of surgery vs nonsurgical approaches to metabolic conditions such as diabetes in patients with baseline body mass index 30–35 kg/m2 (Maggard-Gibbons et al, JAMA).7

Surgery led to greater reductions in body mass index, hemoglobin A1C, hypertension, low-density-lipoprotein cholesterol, and triglycerides. Surgical mortality was 0.0–0.3% and the authors concluded, "Adverse events of surgery were relatively low," and "Most surgical complications were minor and tended not to require major intervention."7

Dr. Schauer referred to a meta-analysis of surgery vs lifestyle and medical care by Rubino et al in the June 2016 issue of Diabetes Care.8 The meta-analysis provided level 1A evidence that surgical superiority was similar in patients with body mass index 35 kg/m2 and lower and those with body mass index over 35 kg/m2. He also referred to the article in the same issue on mechanisms of diabetes improvement following metabolic surgery by Batterham and Cummings.9

These investigators cited the following effects of surgery on glucose homeostasis:

  • Improved beta cell function/functional beta cell mass
  • Improved insulin sensitivity
  • Reduced hepatic glucose production
  • Increased glucose utilization
  • Increased glucose effectiveness

Gaps in the Evidence for Surgery
Dr. Schauer identified the following gaps in the evidence for surgery for patients with type 2 diabetes and obesity:

  • Durability of glycemic improvement for longer than 5 years has not been demonstrated in randomized clinical trials
  • Randomized clinical trials have not been powered to demonstrate a reduction in microvascular and macrovascular complications of type 2 diabetes
  • Most medications for type 2 diabetes share the same gaps in evidence as those for surgical management

The Alliance of Randomized trials of Medicine vs Metabolic Surgery in type 2 diabetes (ARMMS-T2D) is a collaborative effort to fill some of these gaps. The alliance is funded by Ethicon/Medtronics and participating centers are:

  • Cleveland Clinic
  • Brigham and Women's Hospital
  • Joslin Diabetes Center
  • University of Washington
  • University of Pittsburgh
  • Cleveland Clinic Coordinating Center for Clinical Research (C5 Research)

An algorithm authored by Rubino et al was published in the June 2016 issue of Diabetes Care. The algorithm was entitled, Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations. A summary of the algorithm is the following:8

Metabolic surgery for patients with type 2 diabetes should be:

  • Recommended in patients with body mass index ≥40 regardless of glycemic control
  • Recommended in patients with body mass index ≥35 with inadequately controlled hyperglycemia
  • Considered for patients with body mass index 30–34.9 with inadequately controlled hyperglycemia
  • Considered for Asians with body mass index as low as 27.5 with inadequately controlled hyperglycemia

Conclusion
Dr. Schauer concluded that numerous randomized clinical trials and large, long-term prospective studies with hard outcomes are available to inform policy concerning metabolic surgery for type 2 diabetes. The high-quality evidence points to a relatively safe and effective treatment for type 2 diabetes. Widely endorsed international guidelines also include evidence-based recommendations for surgery to treat type 2 diabetes and its comorbidities.

Source
Schauer PR. Session: 3-CT-SY25 - Metabolic Surgery—Is It Ready for Prime Time? 3-CT-SY25 - What Is the Evidence in Support of Metabolic Surgery for the Treatment of Type 2 Diabetes? 76th Scientific Sessions of the American Diabetes Association, June 10-14, New Orleans, LA.

References
1. Cefalu WT, Rubino F, Cummings DE. Metabolic surgery for type 2 diabetes: Changing the landscape of diabetes care. Diabetes Care. 2016;39:857-860.

2. Vest AR, Heneghan HM, Agarwall S, Schauer PR, et al. Bariatric surgery and cardiovascular outcomes: a systematic review. Heart. doi:10.1136/heartjnl-2012-301778.

3. Brethauer SA, Aminian A, Romero-Talamás H, Batayyah E, et al. Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus. Ann Surg. 2013;258(4):628-636.

4. Sjöström L, Narbro K, Sjöström D, Karason K, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357:741-752.

5. Aminian A, Brethauer SA, Kirwan JP, Kashyap SR, et al. How safe is metabolic/diabetes surgery? Diabetes Obes Metab. 2015;17(2):198-201.

6. Cummings DE, Cohen RV. Bariatric/metabolic surgery to treat type 2 diabetes in patients with a BMI <35 kg/m2. Diabetes Care. 2016;39(6):924-933.

7. Maggard-Gibbons M, Maglione M, Livhits M, Ewing B, et al. Bariatric surgery for weight loss and glycemic control in nonmorbidly obese adults with diabetes: A systematic review. JAMA. 2013;309(21):2250-2261.

8. Rubino F, Nathan DM, Eckel RH, Schauer PR, et al. Metabolic surgery in the treatment algorithm for type 2 diabetes: A joint statement by international diabetes organizations. Diabetes Care. 2016;39(6):861-877.

9. Batterham RL, Cummings DE. Mechanisms of diabetes improvement following bariatric/metabolic surgery. Diabetes Care. 2016;39(6):893-901.

Disclosures
P.R. Schauer: Board Member; Speaker; SE Quallity Healthcare Consulting, LLC, Surgi Quest. Consultant; Speaker; Ethicon Endo-Surgery, Inc. Research Support; Speaker; Covidien, Ethicon Endo-Surgery, Inc., Pacira Pharmaceuticals, Inc. Stock/Shareholder; Speaker; SE Quality Healthcare Consulting, LLC, Surgi Quest.
 

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