Gastric bypass helps poorly controlled type 2 diabetes

In patients with mild to moderate obesity and poorly controlled type 2 diabetes, adding Roux-en-Y gastric bypass surgery to intensive lifestyle and medical management more than doubles the likelihood of achieving weight-loss and metabolic goals within 1 year, according to the results of a randomized trial reported in the June 5 issue of JAMA.

However, this potential benefit must be weighed against what appears to be a moderate risk of serious adverse events, even when the procedure is done by experienced medical teams, said Dr. Sayeed Ikramuddin of the department of surgery, University of Minnesota, Minneapolis, and his associates.

In addition, the permanence of weight loss and metabolic results following the first 1-2 years after the procedure remains uncertain, as do long-term adverse events, because so few studies have adequately followed patients past that point, the investigators wrote.

Dr. Ikramuddin and his colleagues drew these conclusions from their randomized trial of 120 patients with mild to moderate obesity (body mass index, 30.0-39.9 kg/m²) whose type 2 diabetes was poorly controlled on standard medical therapy.

In a separate report in the same issue of JAMA, Dr. Melinda Maggard-Gibbons of the University of California, Los Angeles, and her associates reported their findings from a systematic review of the literature regarding all types of bariatric surgery in similar patients with mild obesity (BMI, 30-35). They found that there still is not sufficient evidence to determine whether bariatric surgery is warranted in this patient population because of the lack of long-term data on safety and efficacy. They identified only four studies with a follow-up of more than 2 years, and those had small sample sizes or poor methodology that "preclude definitive conclusions."

Thus, neither of these investigations can support or refute the suggestion by some proponents that bariatric surgery should be extended to diabetic patients with low-grade obesity to improve their glycemic control.

In their prospective, unblinded clinical trial, Dr. Ikramuddin and his associates offered a free, intensive lifestyle and medical-therapy weight control program to the 120 study subjects at one academic medical center in Minnesota, one in New York, and two in Taiwan over a 3-year period. All patients were between 30 and 67 years of age and had hemoglobin A_1c (HbA_1c) levels of 8% or higher (mean, 9.6%); the average duration of diabetes was 9 years.

The program included daily weigh-ins and detailed diaries of eating and exercise, with caloric intake goals of 1,200-1,800 kcal/day and moderate physical activity for at least 325 min/week to achieve a weight loss of 1-2 pounds/week. The study subjects met regularly with trained interventionists to discuss weight management and to enhance adherence.

Patients could add orlistat or, until it was withdrawn from the market, sibutramine for weight control. Medications for glycemic control were added as necessary, as were aspirin therapy and medications to control cholesterol levels and blood pressure.

Half of the study subjects were then randomly assigned to undergo laparoscopic Roux-en-Y gastric bypass. This group was given multivitamin and mineral supplements.

The endpoint of the study was a triple outcome endorsed by the American Diabetes Association: an HbA_1c level of less than 7%, a low-density lipoprotein (LDL) cholesterol level of less than 100 mg/dL, and a systolic blood pressure of less than 130 mm Hg at 1-year follow-up.

A total of 28 patients (49%) in the gastric bypass group achieved this end point, compared with only 11 (19%) in the lifestyle/medical management group, Dr. Ikramuddin and his colleagues reported (JAMA 2013;309:2240-49).

Of these three components of the combined endpoint, only HbA_1c level showed a significant difference between the two study groups: 43 (75%) of the surgery group achieved an HbA_1c level under 7%, compared with just 18 (32%) of the lifestyle/medical management group.

The difference in outcomes between the two groups was attributed chiefly to their difference in weight loss. The mean loss at 1 year was 26% of baseline weight after gastric bypass, compared with 8% with the intensive lifestyle/medication program.

Patients in the surgery group continued to lose weight throughout the year of follow-up, while those in the other group tended to lose weight during the first 6 months and plateau after that.

On average, at 1 year the patients in the surgery group required three fewer medications than did those in the other group to manage glycemia, dyslipidemia, and hypertension.

However, patients who underwent gastric bypass had 50% more serious adverse events and 55% more nonserious adverse events than did those who did not. "All surgeons performing gastric bypass in this study were experts; thus the occurrence of serious complications must be factored into the design of larger trials of effectiveness for patients with moderate obesity," Dr. Ikramuddin and his associates said.

The 22 serious adverse events in the surgery group included 4 perioperative and 6 late postoperative complications. The most serious complications involved anastomotic leakage that was not detected on routine postoperative upper-GI contrast studies. One of these patients eventually required extracorporeal membrane oxygenation; she developed anoxic brain injury, required lower-extremity amputation, and remains permanently disabled.

Nutritional deficiencies also developed relatively often in the bypass group, despite supplementation. These included iron, vitamin B, and vitamin D deficiencies, as well as hypoalbuminemia.

Other adverse events known to develop more than 1 year after gastric bypass include weight regain, internal hernias, anastomotic ulcers, hypoglycemia, anastomotic strictures, bleeding, bowel obstruction, kidney stones, and fractures.

Overall, these findings show that "the merit of gastric bypass treatment of moderately obese patients with type 2 diabetes depends on whether potential benefits make [these] risks acceptable," the investigators said.

In their systematic review of the literature, Dr. Maggard-Gibbons and her associates reviewed 1,291 studies but could find only 3 randomized trials that came close to directly comparing surgical against nonsurgical interventions in patients with BMIs of 30-35. The total number of patients in these trials was only 290, and individual-level data were available only for 13 patients with type 2 diabetes in this weight category.

They then altered their search criteria to include studies of patients with BMIs of 35-40 and studies that did not directly compare outcomes between surgical and nonsurgical approaches. Even then, "many of the studies were from single surgeons at single academic institutions and may not be representative of results in a general population of patients and surgeons."

Of greatest concern was the fact that "we found no long-term studies of postsurgery adverse events in patients with diabetes within our target BMI range," they said (JAMA 2013;309:2250-61).

The limited studies that were available consistently found that short-term weight loss and glycemic control were better for patients treated with bariatric surgery than for those who were not. However, the durability of these results is uncertain, and the amount of weight loss did not always correlate with the degree of improvement of metabolic factors. And it is not yet known whether these outcomes translate into reduction in the important macrovascular and microvascular effects of diabetes.

Moreover, although surgical complications were not common, those that did occur often were serious and required significant intervention. And of the few studies that did track later complications, most were not designed to do so and covered only "surgeon-reported outcomes from selected, experienced centers."

Thus, "the evidence is insufficient to reach conclusions about the appropriate use of bariatric surgery in this patient population, [and] performance of these procedures in this target population should be under close scientific scrutiny," Dr. Maggard-Gibbons and her colleagues said.

Dr. Irkamuddin’s study was supported by Covidien and the National Center for Advancing Translational Sciences. Dr. Irkamuddin reported ties to Novo Nordisk, USGI, and other companies; his associates reported ties to numerous industry sources. Dr. Maggard-Gibbons’ study was supported by the Agency for Healthcare Research and Quality; she and her associates reported no relevant financial conflicts of interest.

In patients with mild to moderate obesity and poorly controlled type 2 diabetes, adding Roux-en-Y gastric bypass surgery to intensive lifestyle and medical management more than doubles the likelihood of achieving weight-loss and metabolic goals within 1 year, according to the results of a randomized trial reported in the June 5 issue of JAMA.

However, this potential benefit must be weighed against what appears to be a moderate risk of serious adverse events, even when the procedure is done by experienced medical teams, said Dr. Sayeed Ikramuddin of the department of surgery, University of Minnesota, Minneapolis, and his associates.

In addition, the permanence of weight loss and metabolic results following the first 1-2 years after the procedure remains uncertain, as do long-term adverse events, because so few studies have adequately followed patients past that point, the investigators wrote.

Dr. Ikramuddin and his colleagues drew these conclusions from their randomized trial of 120 patients with mild to moderate obesity (body mass index, 30.0-39.9 kg/m²) whose type 2 diabetes was poorly controlled on standard medical therapy.

In a separate report in the same issue of JAMA, Dr. Melinda Maggard-Gibbons of the University of California, Los Angeles, and her associates reported their findings from a systematic review of the literature regarding all types of bariatric surgery in similar patients with mild obesity (BMI, 30-35). They found that there still is not sufficient evidence to determine whether bariatric surgery is warranted in this patient population because of the lack of long-term data on safety and efficacy. They identified only four studies with a follow-up of more than 2 years, and those had small sample sizes or poor methodology that "preclude definitive conclusions."

Thus, neither of these investigations can support or refute the suggestion by some proponents that bariatric surgery should be extended to diabetic patients with low-grade obesity to improve their glycemic control.

In their prospective, unblinded clinical trial, Dr. Ikramuddin and his associates offered a free, intensive lifestyle and medical-therapy weight control program to the 120 study subjects at one academic medical center in Minnesota, one in New York, and two in Taiwan over a 3-year period. All patients were between 30 and 67 years of age and had hemoglobin A_1c (HbA_1c) levels of 8% or higher (mean, 9.6%); the average duration of diabetes was 9 years.

The program included daily weigh-ins and detailed diaries of eating and exercise, with caloric intake goals of 1,200-1,800 kcal/day and moderate physical activity for at least 325 min/week to achieve a weight loss of 1-2 pounds/week. The study subjects met regularly with trained interventionists to discuss weight management and to enhance adherence.

Patients could add orlistat or, until it was withdrawn from the market, sibutramine for weight control. Medications for glycemic control were added as necessary, as were aspirin therapy and medications to control cholesterol levels and blood pressure.

Half of the study subjects were then randomly assigned to undergo laparoscopic Roux-en-Y gastric bypass. This group was given multivitamin and mineral supplements.

The endpoint of the study was a triple outcome endorsed by the American Diabetes Association: an HbA_1c level of less than 7%, a low-density lipoprotein (LDL) cholesterol level of less than 100 mg/dL, and a systolic blood pressure of less than 130 mm Hg at 1-year follow-up.

A total of 28 patients (49%) in the gastric bypass group achieved this end point, compared with only 11 (19%) in the lifestyle/medical management group, Dr. Ikramuddin and his colleagues reported (JAMA 2013;309:2240-49).

Of these three components of the combined endpoint, only HbA_1c level showed a significant difference between the two study groups: 43 (75%) of the surgery group achieved an HbA_1c level under 7%, compared with just 18 (32%) of the lifestyle/medical management group.

The difference in outcomes between the two groups was attributed chiefly to their difference in weight loss. The mean loss at 1 year was 26% of baseline weight after gastric bypass, compared with 8% with the intensive lifestyle/medication program.

Patients in the surgery group continued to lose weight throughout the year of follow-up, while those in the other group tended to lose weight during the first 6 months and plateau after that.

On average, at 1 year the patients in the surgery group required three fewer medications than did those in the other group to manage glycemia, dyslipidemia, and hypertension.

However, patients who underwent gastric bypass had 50% more serious adverse events and 55% more nonserious adverse events than did those who did not. "All surgeons performing gastric bypass in this study were experts; thus the occurrence of serious complications must be factored into the design of larger trials of effectiveness for patients with moderate obesity," Dr. Ikramuddin and his associates said.

The 22 serious adverse events in the surgery group included 4 perioperative and 6 late postoperative complications. The most serious complications involved anastomotic leakage that was not detected on routine postoperative upper-GI contrast studies. One of these patients eventually required extracorporeal membrane oxygenation; she developed anoxic brain injury, required lower-extremity amputation, and remains permanently disabled.

Nutritional deficiencies also developed relatively often in the bypass group, despite supplementation. These included iron, vitamin B, and vitamin D deficiencies, as well as hypoalbuminemia.

Other adverse events known to develop more than 1 year after gastric bypass include weight regain, internal hernias, anastomotic ulcers, hypoglycemia, anastomotic strictures, bleeding, bowel obstruction, kidney stones, and fractures.

Overall, these findings show that "the merit of gastric bypass treatment of moderately obese patients with type 2 diabetes depends on whether potential benefits make [these] risks acceptable," the investigators said.

In their systematic review of the literature, Dr. Maggard-Gibbons and her associates reviewed 1,291 studies but could find only 3 randomized trials that came close to directly comparing surgical against nonsurgical interventions in patients with BMIs of 30-35. The total number of patients in these trials was only 290, and individual-level data were available only for 13 patients with type 2 diabetes in this weight category.

They then altered their search criteria to include studies of patients with BMIs of 35-40 and studies that did not directly compare outcomes between surgical and nonsurgical approaches. Even then, "many of the studies were from single surgeons at single academic institutions and may not be representative of results in a general population of patients and surgeons."

Of greatest concern was the fact that "we found no long-term studies of postsurgery adverse events in patients with diabetes within our target BMI range," they said (JAMA 2013;309:2250-61).

The limited studies that were available consistently found that short-term weight loss and glycemic control were better for patients treated with bariatric surgery than for those who were not. However, the durability of these results is uncertain, and the amount of weight loss did not always correlate with the degree of improvement of metabolic factors. And it is not yet known whether these outcomes translate into reduction in the important macrovascular and microvascular effects of diabetes.

Moreover, although surgical complications were not common, those that did occur often were serious and required significant intervention. And of the few studies that did track later complications, most were not designed to do so and covered only "surgeon-reported outcomes from selected, experienced centers."

Thus, "the evidence is insufficient to reach conclusions about the appropriate use of bariatric surgery in this patient population, [and] performance of these procedures in this target population should be under close scientific scrutiny," Dr. Maggard-Gibbons and her colleagues said.

Dr. Irkamuddin’s study was supported by Covidien and the National Center for Advancing Translational Sciences. Dr. Irkamuddin reported ties to Novo Nordisk, USGI, and other companies; his associates reported ties to numerous industry sources. Dr. Maggard-Gibbons’ study was supported by the Agency for Healthcare Research and Quality; she and her associates reported no relevant financial conflicts of interest.

In patients with mild to moderate obesity and poorly controlled type 2 diabetes, adding Roux-en-Y gastric bypass surgery to intensive lifestyle and medical management more than doubles the likelihood of achieving weight-loss and metabolic goals within 1 year, according to the results of a randomized trial reported in the June 5 issue of JAMA.

However, this potential benefit must be weighed against what appears to be a moderate risk of serious adverse events, even when the procedure is done by experienced medical teams, said Dr. Sayeed Ikramuddin of the department of surgery, University of Minnesota, Minneapolis, and his associates.

In addition, the permanence of weight loss and metabolic results following the first 1-2 years after the procedure remains uncertain, as do long-term adverse events, because so few studies have adequately followed patients past that point, the investigators wrote.

Dr. Ikramuddin and his colleagues drew these conclusions from their randomized trial of 120 patients with mild to moderate obesity (body mass index, 30.0-39.9 kg/m²) whose type 2 diabetes was poorly controlled on standard medical therapy.

In a separate report in the same issue of JAMA, Dr. Melinda Maggard-Gibbons of the University of California, Los Angeles, and her associates reported their findings from a systematic review of the literature regarding all types of bariatric surgery in similar patients with mild obesity (BMI, 30-35). They found that there still is not sufficient evidence to determine whether bariatric surgery is warranted in this patient population because of the lack of long-term data on safety and efficacy. They identified only four studies with a follow-up of more than 2 years, and those had small sample sizes or poor methodology that "preclude definitive conclusions."

Thus, neither of these investigations can support or refute the suggestion by some proponents that bariatric surgery should be extended to diabetic patients with low-grade obesity to improve their glycemic control.

In their prospective, unblinded clinical trial, Dr. Ikramuddin and his associates offered a free, intensive lifestyle and medical-therapy weight control program to the 120 study subjects at one academic medical center in Minnesota, one in New York, and two in Taiwan over a 3-year period. All patients were between 30 and 67 years of age and had hemoglobin A_1c (HbA_1c) levels of 8% or higher (mean, 9.6%); the average duration of diabetes was 9 years.

The program included daily weigh-ins and detailed diaries of eating and exercise, with caloric intake goals of 1,200-1,800 kcal/day and moderate physical activity for at least 325 min/week to achieve a weight loss of 1-2 pounds/week. The study subjects met regularly with trained interventionists to discuss weight management and to enhance adherence.

Patients could add orlistat or, until it was withdrawn from the market, sibutramine for weight control. Medications for glycemic control were added as necessary, as were aspirin therapy and medications to control cholesterol levels and blood pressure.

Half of the study subjects were then randomly assigned to undergo laparoscopic Roux-en-Y gastric bypass. This group was given multivitamin and mineral supplements.

The endpoint of the study was a triple outcome endorsed by the American Diabetes Association: an HbA_1c level of less than 7%, a low-density lipoprotein (LDL) cholesterol level of less than 100 mg/dL, and a systolic blood pressure of less than 130 mm Hg at 1-year follow-up.

A total of 28 patients (49%) in the gastric bypass group achieved this end point, compared with only 11 (19%) in the lifestyle/medical management group, Dr. Ikramuddin and his colleagues reported (JAMA 2013;309:2240-49).

Of these three components of the combined endpoint, only HbA_1c level showed a significant difference between the two study groups: 43 (75%) of the surgery group achieved an HbA_1c level under 7%, compared with just 18 (32%) of the lifestyle/medical management group.

The difference in outcomes between the two groups was attributed chiefly to their difference in weight loss. The mean loss at 1 year was 26% of baseline weight after gastric bypass, compared with 8% with the intensive lifestyle/medication program.

Patients in the surgery group continued to lose weight throughout the year of follow-up, while those in the other group tended to lose weight during the first 6 months and plateau after that.

On average, at 1 year the patients in the surgery group required three fewer medications than did those in the other group to manage glycemia, dyslipidemia, and hypertension.

However, patients who underwent gastric bypass had 50% more serious adverse events and 55% more nonserious adverse events than did those who did not. "All surgeons performing gastric bypass in this study were experts; thus the occurrence of serious complications must be factored into the design of larger trials of effectiveness for patients with moderate obesity," Dr. Ikramuddin and his associates said.

The 22 serious adverse events in the surgery group included 4 perioperative and 6 late postoperative complications. The most serious complications involved anastomotic leakage that was not detected on routine postoperative upper-GI contrast studies. One of these patients eventually required extracorporeal membrane oxygenation; she developed anoxic brain injury, required lower-extremity amputation, and remains permanently disabled.

Nutritional deficiencies also developed relatively often in the bypass group, despite supplementation. These included iron, vitamin B, and vitamin D deficiencies, as well as hypoalbuminemia.

Other adverse events known to develop more than 1 year after gastric bypass include weight regain, internal hernias, anastomotic ulcers, hypoglycemia, anastomotic strictures, bleeding, bowel obstruction, kidney stones, and fractures.

Overall, these findings show that "the merit of gastric bypass treatment of moderately obese patients with type 2 diabetes depends on whether potential benefits make [these] risks acceptable," the investigators said.

In their systematic review of the literature, Dr. Maggard-Gibbons and her associates reviewed 1,291 studies but could find only 3 randomized trials that came close to directly comparing surgical against nonsurgical interventions in patients with BMIs of 30-35. The total number of patients in these trials was only 290, and individual-level data were available only for 13 patients with type 2 diabetes in this weight category.

They then altered their search criteria to include studies of patients with BMIs of 35-40 and studies that did not directly compare outcomes between surgical and nonsurgical approaches. Even then, "many of the studies were from single surgeons at single academic institutions and may not be representative of results in a general population of patients and surgeons."

Of greatest concern was the fact that "we found no long-term studies of postsurgery adverse events in patients with diabetes within our target BMI range," they said (JAMA 2013;309:2250-61).

The limited studies that were available consistently found that short-term weight loss and glycemic control were better for patients treated with bariatric surgery than for those who were not. However, the durability of these results is uncertain, and the amount of weight loss did not always correlate with the degree of improvement of metabolic factors. And it is not yet known whether these outcomes translate into reduction in the important macrovascular and microvascular effects of diabetes.

Moreover, although surgical complications were not common, those that did occur often were serious and required significant intervention. And of the few studies that did track later complications, most were not designed to do so and covered only "surgeon-reported outcomes from selected, experienced centers."

Thus, "the evidence is insufficient to reach conclusions about the appropriate use of bariatric surgery in this patient population, [and] performance of these procedures in this target population should be under close scientific scrutiny," Dr. Maggard-Gibbons and her colleagues said.

Dr. Irkamuddin’s study was supported by Covidien and the National Center for Advancing Translational Sciences. Dr. Irkamuddin reported ties to Novo Nordisk, USGI, and other companies; his associates reported ties to numerous industry sources. Dr. Maggard-Gibbons’ study was supported by the Agency for Healthcare Research and Quality; she and her associates reported no relevant financial conflicts of interest.