Prepared for: Agency for Healthcare Research and Quality (AHRQ) ahrq

1. Comparative Effectiveness of Bariatric Surgery and Nonsurgical Therapy in Adults With Metabolic Conditions and a Body Mass Index of 30.0 to 34.9 kg/m2 Prepared for: Agency for Healthcare Research and Quality (AHRQ) www.ahrq.gov

2. Outline of Material • Introduction to bariatric surgery and its role in the management of obesity and associated metabolic conditions • Systematic review methods • The clinical questions addressed by the comparative effectiveness review • Results of studies and evidence-based conclusions about the comparative effectiveness and safety of various bariatric surgical procedures in adults with metabolic conditions and a body mass index of 30.0 to 34.9 kg/m2 • Gaps in knowledge and future research needs • What to discuss with patients and their caregivers Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

3. Background:Definition and Types of Bariatric Surgery • Bariatric surgery or weight-loss surgery refers to surgery usually performed in patients with a body mass index (BMI) of 40 kg/m2 or greater and those with a BMI between 35 and 40 kg/m2 and a major medical comorbidity in order to: • Support weight loss • Treat or prevent obesity-related comorbidities (e.g., diabetes, hypertension, cardiovascular disease, obstructive sleep apnea) • The most common types of bariatric surgery include: • Laparoscopic adjustable gastric banding (LAGB) • Roux-en-Y gastric bypass (RYGB) • Sleeve gastrectomy • Biliopancreatic diversion with duodenal switch (BPD/DS) Buchwald H, Estok R, Fahrbach K, et al. Am J Med. 2009 Mar;122(3):248-256. PMID: 19272486. Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

4. Background: Role of Bariatric Surgery in Managing Obesity and Associated Metabolic Conditions • Studies show that bariatric surgery causes significant weight loss and is more effective at improving diabetes in the short term (up to 2 years) than nonsurgical interventions (diet, exercise, other behavioral interventions, and medications). • Diabetes improvement starts rapidly after surgery, before significant weight loss has occurred. • The mechanism for postoperative metabolic improvements has not been fully elucidated and may be, in part, independent of weight loss. • This suggests that bariatric surgery may improve metabolic comorbidities even in patients who are not morbidly obese. Buchwald H, Estok R, Fahrbach K, et al. Am J Med. 2009 Mar;122(3):248-256. PMID: 19272486. Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm. Mingrone G, Panunzi S, De Gaetano A, et al. N Engl J Med. 2012 Mar 26;366(17):1577-85. PMID: 22449317.

5. Background: Uncertainties Related to the Role of Bariatric Surgery in Patients With Lower BMIs and Metabolic Conditions • In recent years, bariatric surgery has been suggested as an option for patients with lower body mass indexes (BMIs; at least 30 kg/m2 but less than 35 kg/m²) as a way to treat diabetes and other metabolic conditions. • However, there is a lack of consensus regarding the minimum BMI requirement. • Additionally, there remain uncertainties about the comparative effectiveness of different bariatric surgical procedures, especially in the long term. • This review assessed the relative risks and benefits of the various surgical and conventional approaches to treating diabetes or impaired glucose tolerance in patients with a BMI of 30.0 to 34.9 kg/m². International Diabetes Federation Taskforce on Epidemiology and Prevention. Available at www.idf.org/webdata/docs/IDF-Position-Statement-Bariatric-Surgery.pdf. Accessed July 2013. Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm. U.S. Food and Drug Administration. Available at www.fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm245617.htm. Accessed July 2013.

6. Agency for Healthcare Research and Quality (AHRQ) Comparative Effectiveness Review (CER) Development • Topics are nominated through a public process, which includes submissions from health care professionals, professional organizations, the private sector, policymakers, members of the public, and others. • A systematic review of all relevant clinical studies is conducted by independent researchers, funded by AHRQ, to synthesize the evidence in a report summarizing what is known and not known about the select clinical issue. The research questions and the results of the report are subject to expert input, peer review, and public comment. • The results of these reviews are summarized into Clinician Research Summaries and Consumer Research Summaries for use in decisionmaking and in discussions with patients. • The Research Summaries and the full report, with references for included and excluded studies, are available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

7. Clinical Questions Addressed by This Comparative Effectiveness Review (1 of 3) • Key Question 1. What does the evidence show regarding the comparative effectiveness of bariatric surgery for treating adult patients with a body mass index (BMI) of 30.0 to 34.9 kg/m² and metabolic conditions, including diabetes? Are certain surgical procedures more effective than others (laparoscopic adjustable gastric banding, gastric bypass, or sleeve gastrectomy)? • Key Question 2. What does the evidence show regarding the comparative effectiveness of bariatric surgery versus conventional nonsurgical therapies for treating adult patients with a BMI of 30.0 to 34.9 kg/m² and metabolic conditions? Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

8. Clinical Questions Addressed by This Comparative Effectiveness Review (2 of 3) • Key Question 3. What are the potential short-term adverse effects and/or complications associated with bariatric surgery for treating adult patients with a body mass index (BMI) of 30.0 to 34.9 kg/m² who have metabolic conditions? • Key Question 4. Does the evidence show racial and demographic disparities with regard to potential benefits and harms associated with bariatric surgery for treating adult patients with a BMI of 30.0 to 34.9 kg/m² and metabolic conditions? What other patient factors (social support, counseling, preoperative weight loss, and compliance with recommended treatment) are related to successful outcomes? Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

9. Clinical Questions Addressed by This Comparative Effectiveness Review (3 of 3) • Key Question 5. What does the evidence show regarding long-term benefits and harms of bariatric surgery for treating adult patients with a body mass index of 30.0 to 34.9 kg/m² and who have metabolic conditions? How do the long-term benefits and harms of bariatric surgery compare to short-term outcomes (within 1 year after surgery)? Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

10. Rating the Strength of Evidence From the Comparative Effectiveness Review • The strength of evidence was classified into four broad categories: Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

11. Evidence for the Benefits of Bariatric Surgery in Adults With Metabolic Conditions and a BMI of 30.0 to 34.9 kg/m2 (1 of 3) • Bariatric surgery is an effective treatment for weight-control and glucose-control outcomes in patients with diabetes and impaired glucose tolerance in the short term (up to 2 years). The strength of evidence varies depending on the bariatric surgical procedure used: • Laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, or sleeve gastrectomy Strength of Evidence: Moderate • Biliopancreatic diversion with duodenal switch Strength of Evidence: Low BMI = body mass index Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

12. Evidence for the Benefits of Bariatric Surgery in Adults With Metabolic Conditions and a BMI of 30.0 to 34.9 kg/m2 (2 of 3) • In patients with diabetes or impaired glucose tolerance who have undergone bariatric surgery, improvements in glucose control outcomes can be measured as early as 1 month after surgery; however, this effect is not seen in all patients. Strength of Evidence: Moderate • At 1 year after bariatric surgery, decreases in both weight and hemoglobin A1c are greater than typically achieved in studies of diet, exercise, or other behavioral interventions (please see the tables in the next two slides for details). Strength of Evidence: Moderate Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

13. Outcomes of Surgical and Nonsurgical Treatments in Adults With Metabolic Conditions and a Body Mass Index of 30.0 to 34.9 kg/m2: Weight and Hemoglobin A1c Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

14. Outcomes of Surgical and Nonsurgical Treatments in Adults With Metabolic Conditions and a Body Mass Index of 30.0 to 34.9 kg/m2: Other Metabolic Outcomes Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

15. Outcomes of Surgical and Nonsurgical Treatments in Adults With Metabolic Conditions and a Body Mass Index of 30.0 to 34.9 kg/m2: Prevention of Diabetes Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

16. Evidence for the Benefits of Bariatric Surgery in Adults With Metabolic Conditions and a Body Mass Index of 30.0 to 34.9 kg/m2 • Several studies report improvements in hypertension and cholesterol at 1 year after bariatric surgery. Strength of Evidence: Low • The evidence is insufficient to permit conclusions about the effectiveness of bariatric surgery, when compared with other interventions, regarding these outcomes: • Continued weight loss or weight maintenance in the long term (more than 2 years) • Hemoglobin A1c ˜˜™levels in the long term (more than 2 years) • Prevention of diabetes • Microvascular and macrovascular outcomes Strength of Evidence: Insufficient Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

17. Evidence for the Adverse Effects of Bariatric Surgery in Adults With Metabolic Conditions and a Body Mass Index of 30.0 to 34.9 kg/m2 (1 of 2) • Complications of laparoscopic adjustable gastric banding reported in more than one study include: • ††Band slippage (2.3%) • Port or tube problems and band erosion (2%) • Postsurgical pouch dilation (5.4%) • Reflux/hiatal hernia (2.7%) †Strength of Evidence: Low • Complications of Roux-en-Y gastric bypass reported in more than one study include: • Stricture (5%) • Ulcers (9%) • Incisional hernias (4.5%) • Wound infections (4.3%) ˜™™„„ ˜™™Strength of Evidence for All Bariatric Procedures: Low Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

18. Evidence for the Adverse Effects of Bariatric Surgery in Adults With Metabolic Conditions and a Body Mass Index of 30.0 to 34.9 kg/m2 (2 of 2) • The surgical complication rates for sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB) are similar. However, the types of complications observed with these two procedures might vary. Strength of Evidence: Low • Although the reported rates of mortality are low in this population (rate of mortality is 0.48% for laparoscopic adjustable gastric banding and 0.0 percent for gastric sleeve, RYGB, and biliopancreatic diversion), studies are too limited to accurately predict risks. „Strength of Evidence: Low • The evidence is insufficient to evaluate adverse effects of bariatric surgery in the long term (beyond 2 years) for patients with diabetes or impaired glucose tolerance. Strength of Evidence: Insufficient Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

19. Other Findings of the ComparativeEffectiveness Review • The evidence is insufficient to permit conclusions about how the effectiveness and safety of bariatric surgical procedures compare with each other as treatment for diabetes or impaired glucose tolerance (IGT) in patients with a BMI of 30.0 to 34.9 kg/m2. „„Strength of Evidence: Insufficient • The evidence is insufficient to know if racial or demographic disparities affect the potential benefits and adverse effects of bariatric surgery in patients with a BMI of 30.0 to 34.9 kg/m2 and diabetes or IGT. Strength of Evidence: Insufficient • The evidence is insufficient to determine if other patient factors (social support, counseling, preoperative weight loss, or treatment compliance) are related to successful postsurgical outcomes. Strength of Evidence: Insufficient Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

20. Bariatric Surgery in Adults With Metabolic Conditions and a Body Mass Index of 30.0 to 34.9 kg/m2: Other Considerations • There are additional considerations that clinicians should recognize that were not the subject of the systematic review. Depending on the type of bariatric surgery, these considerations might include regular postsurgical monitoring for: • Weight regain • Recurrence of diabetes • Nutritional deficiencies • Other postsurgical complications Mechanick JI, Youdim A, Jones DB, et al. Surg Obes Relat Dis. 2013;9(2):159-91. PMID: 23537696.

21. Conclusions (1 of 3) • Bariatric surgery is an effective treatment for diabetes and impaired glucose tolerance in patients with a body mass index of at least 30 but less than 35 kg/m2 who are followed up to 2 years. • Weight-loss and glucose-control outcomes achieve greater improvement than typically seen with behavioral interventions (e.g., diet, exercise). • Head-to-head comparisons are needed to determine comparative effectiveness among surgical interventions. Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

22. Conclusions (2 of 3) • The rates of short-term adverse effects (cardiovascular, respiratory, gastrointestinal, and metabolic) were low. • Reported complications of laparoscopic adjustable gastric banding include band slippage, leakage, and pouch dilation, and those reported for Roux-en-Y gastric bypass include stricture, ulcers, and rarely hemorrhage. • While not discussed in the review, it has been suggested that weight regain and recurrence of diabetes might be observed after bariatric surgery. Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

23. Conclusions (3 of 3) • Despite promising short-term outcomes, very few studies of this target population have followup durations greater than 2 years. • The long-term effects of bariatric surgical procedures on major clinical endpoints in this patient population with a lower body mass index are not known. • Studies comparing surgical intervention to comprehensive care and behavioral interventions to each other are also needed to determine the relative effectiveness of these strategies in the long term. Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

24. Gaps in Knowledge (1 of 2) • There is a scarcity of high-quality studies for patients with a body mass index of 30.0 to 34.9 kg/m2 and metabolic comorbidities. • Very few studies had long-term followup (more than 2 years). • The effectiveness of bariatric surgery in preventing the clinical consequences of diabetes and its impact on major clinical endpoints such as cardiovascular mortality or morbidity have not been studied. • Of the 54 studies included in the comparative effectiveness review, a very limited number were conducted in the United States, making applicability of findings from studies conducted outside the United States to American patients unclear. Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

25. Gaps in Knowledge (2 of 2) • Quality-of-life and psychological outcomes after surgery were rarely reported. • Most studies were not designed to assess adverse events and reflected events reported by the surgeon or the surgical team. The rates of adverse events in these studies may, therefore, be lower than rates experienced in the wider community. • For all surgical procedures, there is concern that published studies usually come from academic medical centers. Outcomes for patients in these studies may not reflect the outcomes achieved in the wider community. Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.

26. What To Discuss With Your Patients • The possible benefits of bariatric surgery for patients with a body mass index between 30.0 and 34.9 kg/m2 and with diabetes or IGT • The possibility that the patient could be referred to a surgeon who would discuss the different types of bariatric surgery recommended for the patient • The possible adverse effects of bariatric surgery • Whether or not the specific bariatric surgery recommended for the patient would be covered by the patient's insurance and how that would impact the patient's decisionmaking • Lifestyle changes that are necessary to fully benefit from bariatric surgery • Nonsurgical treatment options for diabetes and other metabolic conditions • The expected course of the patient's diabetes with continued nonsurgical therapy Maglione MA, Gibbons MM, Livhits M, et al. AHRQ Comparative Effectiveness Review No. 82. Available at www.effectivehealthcare.ahrq.gov/weight-loss-surgery.cfm.