We have conducted a health technology assessment (HTA) that addresses efficacy, safety and a health-economic evaluation of bariatric surgery for patients with type 2 diabetes and a BMI below 35 compared to standard treatment. We included four randomized and six non-randomized controlled studies as well as one large registry study with no control group.
After two-years of follow-up we found that:
- On average, 44% of patients in the surgery group achieved remission of type 2 diabetes compared to 3% in the control group. We have moderate confidence in the effect estimate.
- On average, HbA1c concentrations were reduced by 1 to 1.5 percentage points more than standard treatment. We have moderate confidence in the effect estimate.
- Fasting glucose concentrations were reduced. We have moderate confidence in the effect estimate.
- Health-related quality of life was only investigated in one study.
- BMI was on average reduced by 4 to 5 kg/m2 more in the surgery group compared to standard treatment. We have moderate confidence in the effect estimate.
No studies reported results for efficacy and safety beyond two years.
- The registry study reported that 30-day mortality, severe morbidity and composite morbidity were 0.15%, 0.7%, and 4.2%, respectively, among 1,300 operated patients.
- ·The estimated cost of bariatric surgery is between 83,500 and 118,000 kroner per patient during the year in which treatment is provided, while lifestyle interventions cost between 23 400 and 52 200 kroner per patient. All costs reflect a healthcare perspective.
Bariatric surgery among individuals with type 2 diabetes and BMI below 35 may lead to remission of diabetes. However, short follow-up in the included studies makes it difficult to predict the long term impact of bariatric surgery on health outcomes and costs for these patients. Efficacy and safety beyond two years should be investigated in further studies.
The division for health services in the Norwegian Institute of Public Health has prepared a health technology assessment (HTA) comparing the effectiveness and safety of bariatric surgery with non-surgical interventions in the treatment of patients with Type 2 Diabetes and a body mass index (BMI) below 35. The report will also include a health economic evaluation of the use of bariatric surgery compared with non-surgical interventions. The HTA is intended to inform decision making by the Norwegian System for New Health Technologies.
We conducted a systematic search for randomized and non-randomized controlled studies in May 2017. For assessment of safety, we also applied for studies without a control group (registry studies) with participant numbers above 500. A Swedish HTA that met our inclusion criteria, with a search from January 2016, was used as a basis for obtaining studies published before 2016. Risk of bias was evaluated for all studies. We used risk ratio (RR) for dichotomy outcomes, weighted mean difference (MD) for continuous outcomes and calculated 95% confidence interval (CI) for the effect estimates. The quality of evidence for each outcome was assessed using the GRADE tool. Confidence in the documentation, i.e., whether we trust that the effect estimate is close to a true underlying effect, is ranked as high, moderate, low or very low..
Results efficacy and safety
We included a total of 11 studies; four randomized (RCT), four prospective and two retrospective non-randomized controlled trials, and one large registry study with no control group. Of the 534 total patients included in the controlled studies, 257 were undergoing or were randomized to bariatric surgery. The registry study included 1,300 operated patients. One RCT and one non-randomized study used surgical methods that are not performed in the Norwegian specialist health care service. Follow-up was one or two years in most studies. Efficacy results were comparable between the randomized and non-randomized studies. Therefore, we only present the results for the meta-analysis of the randomized studies after two years.
Nine out of ten controlled studies found higher rates of diabetes remission, defined as HbA1c values below 6.5%, in the surgery group compared to the control group. Diabetes remission occurred in 26 of 59 patients (44%) in the surgery group versus 2 out of 60 (3%) in the control group (RR = 8.73 [CI 2.52 to 30.17]). Furthermore, we found a significantly lower HbA1c concentration in the surgery group than in the control group with a mean difference of MD = -1.37% (CI -1.98 to -0.76) in favor of surgery. Fasting glucose concentrations were also significantly lower in the surgery group than in the control group (MD = -2.96 mmol/l [CI -5.28 to -0.64]). Health-related quality of life was assessed in only one study. The study found a statistically significant improvement in physical health, measured with the questionnaire SF-36, in the group that underwent band surgery compared to the group receiving drug treatment, but no significant difference between the groups in mental health. Nine out of ten studies found lower BMI or weight measured in kilograms after surgery compared to control treatment. Mean BMI reduction was MD = -4.10 kg/m2 (CI -6.30 to -1.90 to) more in the surgery group than in the control group. In the controlled studies, no deaths were reported in the surgery groups, while one death in the control groups was recorded. The registry study, with data for 1300 operated patients, reported a mortality rate of 0.15%, a serious morbidity of 0.7% and a combined morbidity of 4.2% during a follow-up period of 30 days. Reoperations occurred in 1.6% of patients.
We have moderate confidence in the effect estimates for remission of diabetes, reduction in HbA1c concentrations and BMI.
There were too few studies to do relevant subgroup analyses of weight classes and surgery methods.
Relatively few patients from the included studies received surgery types relevant for use in Norway. Therefore we considered the current documentation of clinical efficacy as insufficient to build a reliable and valid cost-effectiveness model that would reflect Norwegian clinical practice. For the assessment of economic aspects, we performed a cost analysis in a healthcare perspective. We estimated costs associated with bariatric surgery with one-year follow-up to between 83,500 and 118,000 Norwegian kroner (NOK) per patient. The estimate includes surgery costs, consultations, examinations and patient training before and after surgery. Costs associated with standard treatment in the form of intensive lifestyle intervention are estimated to between NOK 23,400 and NOK 52,200 per patient. The costs include outpatient consultations with a physician, nutritionist, sports teacher and group-based teaching in physical activity, diet and motivation. It is uncertain how many patients with type 2 diabetes and KMI under 35 that may be appropriate for surgical treatment.”
We assessed our level of confidence in the effect estimates in this HTA as moderate. It was not possible to blind for the intervention, but we still assumed that this was of minor importance as blood test measurements were regarded as objective goals. The results in the randomized and non-randomized studies were comparable, and surgical methods used in most studies were consistent with Norwegian practice. We therefore considered the results regarding diabetes remission, reduction in HbA1c, fasting glucose levels, and BMI are relevant for the Norwegian health care system.
The greatest limitation of the documentation in this HTA is short follow-up in the included studies. This applies to both effectiveness and safety.
Studies included in our previous report on bariatric surgery for morbid obesity (BMI ≥ 35 with obesity-related disease or BMI ≥ 40), reported diabetes remission in up to 70% to 75% of patients in the surgery groups after two years. One can therefore speculate whether the effect of surgery is lower in patients with diabetes and BMI below 35 compared to patients with morbid obesity. It is also reported that at least 40 percent of the population with morbid obesity who achieved diabetes remission relapsed within 15 years. However, relapse among individuals with BMI below 35 is unknown because of limited two year follow-up.
Bariatric surgery is a radical method for reducing diabetes compared to pharmacological and lifestyle treatments. In the studies included in our analysis, 44% of the surgical patients were in diabetes remission after two years. This also means that approximately 55% did not achieve remission despite surgery, and were thus at risk for side effects from surgery in addition to drug side effects. If bariatric surgery is a potential treatment option for patients with type 2 diabetes and BMI below 35, it is important that clinicians and patients make their choices with the understanding that evidence about the surgical option is limited. Patients should be well informed both about alternative treatment options and the implications of uncertainty around the efficacy and safety of bariatric surgery.
- Long-term follow-up of effectiveness and safety beyond 2 years for patients with type 2 diabetes and BMI below 35.
- Quality of life, pain, anxiety, and depression are thought to be important patient-related outcomes in further research both in the short and long term.
- Relevance of different BMI classes (overweight, obesity grade I, II or II) or type of surgery for remission of type 2 diabetes.
Bariatric surgery in patients with type 2 diabetes and a BMI below 35 can give a remission of diabetes and a lower concentration of HbA1c compared to pharmacological treatment. Confidence in this documentation is moderate. However, short follow-up in the included studies makes it difficult to predict the long term impact of bariatric surgery on health outcomes and costs for these patients. Effectiveness and safety beyond two years should be investigated in further studies.