Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Cohen (2020)

Type of study:
Randomized clinical trial.

Setting and country:
Single center, not reported.

Funding:

The study was supported by research grants from Johnson & Johnson Brasil, Oswaldo Cruz German Hospital, and Science Foundation Ireland and by grant 12/YI/B2480 from Science Foundation Ireland (Dr le Roux) and grant 2015-02733 from the Swedish Medical Research Council (Dr le Roux).

Conflict of interest

Dr Cohen reported receiving grants from Johnson & Johnson Medical Brasil during the conduct of the study. Dr Petry reported receiving grants from Johnson & Johnson Medical Brasil during the conduct of the study. Dr Schiavon reported receiving grants from Ethicon Inc and personal fees from Johnson & Johnson Brasil outside the submitted work. Dr Pompilio reported receiving grants from Johnson & Johnson Medical Brasil during the conduct of the study. Dr Sarian reported receiving grants from Johnson & Johnson Medical Brasil during the conduct of the study. Dr le Roux reported receiving grants from Science Foundation Ireland, Health Research Board, European Federation for Study of Diabetes, and the Swedish Research Council during the conduct of the study and receiving honorarium for lectures and scientific advisory board from Novonordisk, GI Dynamics, Sanofi, Johnson & Johnson Brasil, Keyron, Herbalife, and Boehringer Ingelheim outside the submitted

Inclusion criteria:

• uACR greater than 30 mg/g;
• Type 2 diabetes with glycated hemoglobin levels less than 12% (to convert to proportion of total hemoglobin, multiply by 0.01);
• Age of 18 to 65 years;
• BMI of 30 to 35.

Exclusion criteria:

• Patient’s refusal to participate;
• Autoimmune DM;
• Previous abdominal surgeries that may take surgery more difficult, increasing the surgical risk;
• Previous malabsorptive and restrictive surgeries;
• Pregnant woman and nursing mothers;
• Recent history of neoplasia (<5 years), except for non-melanoma skin neoplasms;
• History of liver disease – liver cirrhosis – active chronic hepatitis, active hepatitis B and hepatitis C;
• Angina;
• Pulmonary embolism or severe thrombophlebitis in the last 2 years;
• Positive HIV serum testing;
• Psychiatric disorders, including dementia, active psychosis, severe depression, history of suicide attempts, use of illicit drugs, and excessive alcohol consumption in the last 12 months;
• Patients with severe retinopathy, nephropathy, and neuropathy (defined as high risk/advanced proliferative retinopathy or amaurosis; stage 5 of chronic kidney disease defined by glomerular filtration rate, patients who need dialysis or renal transplantation; stage 3 of peripheral neuropathy);
• Patients who participated in other clinical trials in the past 30 days.
  
  

N total at baseline:

Intervention: N=51
Control: N=49

Important prognostic factors²:

Age, mean (SD)

I: 52.5 (7.6)

C: 50.2 (7.5)

Sex:

I: 28/51 (55%)

C: 27/49 (55%)

BMI, mean (SD)

I: 32.5 (1.9)

C: 32.6 (2.1)

HbA1c (%), mean (SD)

I: 8.80 (1.86)

C: 8.94 (1.96)

Fasting Glucose (mg/dL), median (IQR)
I: 167 (145 to 208)
C: 174 (142 to 232)

Systolic blood pressure, mean (SD) mmHg

I: 141.5 (17.2)

C: 137.3 (15.5)

Diastolic blood pressure, mean (SD) mmHg, mean (SD)

I: 88.1 (12.7)

C: 85.7 (8.0)

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test):

Roux-en-Y gastric bypass (RYGB)

RYGB was performed laparoscopically by a single surgeon (R.V.C.) and consisted of a 30-mL gastric pouch, a 150-cm alimentary limb, and an 80-cm biliopancreatic limb. The RYGB group received standard supplementation and was assessed for nutritional deficiencies at 6, 12, 18, and 24 months.

Describe control (treatment/procedure/test):

Best medical treatment

Drugs with a beneficial effect on microvascular and macrovascular outcomes were administered early after the trial commenced if patients were not already taking these medications. Use of the drugs was continued in the best medical treatment group even in the event of metabolic targets being met and remission of albuminuria occurring. Use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and statins was continued in the RYGB group irrespective of whether albuminuria remitted. Glucose-lowering drugs, including insulin, were dose adjusted. Metformin treatment was maintained for all patients; however, doses were reduced or metformin use stopped when the HbA1c level was less than 5.7% (39 mmol/mol), the fasting plasma glucose level was less than 100 mg/dL (to convert to millimoles per liter, multiply by 0.0555), or metformin related gastrointestinal adverse effects occurred.

Length of follow-up:

Loss-to-follow-up:

The recruitment period will last for 2 years (24 months) from the beginning of the study (initiation visit), and follow-up will proceed for 60 months after participant inclusion in the study.

I: 51 randomized and analyzed (ITT);

1 lost to follow-up, 1 discontinued intervention

C: 49 randomized and analyzed (ITT);

1 discontinued intervention

Outcome measures and effect size (include 95%CI and p-value if available):

Hba_1c %, mean (SD)

I: 6.18 (1.38)

C: 6.72 (1.34)

Hba_1c level l ≤7.0%, n/N (%)

I: 42/51 (83.0%)

C: 34/49 (70.2%)

Partial remission (Hba_1c level l ≤6.5%, n/N (%))

I: 36/51 (70.9%)

C: 25/49 (50.5%)

Hba_1c level l ≤6.0%, % (95% CI)

I: 23/51 (44.5%)

C: 12/49 (24.4%)

Fasting glucose level, mg/dL

I: 104.1 (95% CI 90.2 to 118.0)

C: 121.6 (95% 108.0 to 135.2)

Complications

Serious adverse events, n/N (%)

I: 6/46 (13%)

C: 6/46 (13%)

P>0.99

No retinopathy, n/N (%)

I: 38/51 (74.1%)

C: 36/49 (73.3%)

Neuropathy, n/N (%)

I: 10/51 (20.3%)

C: 12/49 (25.3%)

Quality of life (SF-36)

“Patients randomized to receive RYGB had a greater improvement in their general health, emotional well-being, physical health, physical role functioning and vitality” (p. 7/11)

Weight loss

Mean % (95% CI) change in body weight

I: -25.4% (95% CI -26.9 to -23.8)

C: -4.5 (95% CI -6.1 to -3.1)

BMI

I: 24.26 (23.51 to 25.01)

C: 31.2 (30.47 to 31.98)

Medication use (diabetic)

Biguanides

I: 35 of the 46

C: 45 of the 46

Thiazolidinediones

I: 9 of the 46

C: 31 of the 46

Incretin mimetics/enhancers

I: 19 of the 46

C: 46 of the 46

SGLT2 Inhibitors

I: 21 of the 46

C: 41 of the 46

Insulin

I: 5 of the 46

C: 25 of the 46

Secretagogues

I: 0 of the 46

C: 2 of the 46

Author’s conclusion

After 24 months, RYGB was more effective than best medical

treatment for achieving remission of albuminuria and stage G1 to G3 and A2 to A3 CKD in

patients with type 2 diabetes and obesity.

Lau (2021)

Type of study:
Open-label, randomized controlled clinical trial.

Setting and country:
Centro Hospitalar São João in Porto, Portugal.

Funding and conflicts of interest:
This research was performed independently of any funding, as part of the institutional activity of the investigators

Inclusion criteria:

• Aged between 20 and 65 years of age;
• BMI equal or more than 30 or equal or less than 35;
• Previous diagnosis of T2D, according to the American Diabetes Association definition, and under antidiabetic medical therapy;
• Duration of diabetes >3 months;
• Overnight-fasting C-peptide >0.7 ng/ml;
• Negative antiGAD autoantibody;
• Possible eligibility for general anesthesia;
• Ability and willingsness to participate in the study, with an understanding of the requirements of each arm of the study (written informed consent).

Exclusion criteria:

• Specific contraindication to obesity surgery;
• Diabetes secondary to a specific disease (maturity-onset diabetes of the young, latent autoimmune diabetes in adult or pancreatitis);
• Having taken any antibiotic, probiotic, or prebiotic agents during the month before randomisation;
• Pregnancy;
• Debilitating disease;
• Any psychological condition which could hamper a patient’s cooperation;
• Any condition which, in the opinion of the researcher, could have meant that participation in the study was risky or could have biased the results.

N total at baseline:

Intervention: N=8
Control: N=10

Important prognostic factors²:

Age, mean (SD)

I: 53.4 (8.78)

C: 58.2 (4.73)

Sex:

I: 4/8 (50%)

C: 3/10 (30%)

BMI, mean (SD)

I: 33.6 (1.84)

C: 32.0 (1.56)

HbA1c (%), mean (SD)

I: 8.69 (1.03)

C: 8.19 (0.56)

Fasting Glucose (mg/dL), mean (SD)
I: 175 (27.9)
C: 164 (43.6)

Groups comparable at baseline? Yes, however, patients who underwent RYGB had signifcantly higher weight, visceral fat area, body fat mass, and serum hsCRP at baseline.

Describe intervention (treatment/procedure/test):

Roux-en-Y gastric bypass (RYGB)

Describe control (treatment/procedure/test):

Medical therapy, including lifestyle

Length of follow-up:

Loss-to-follow-up:

1 year

2 patients in the surgical arm discontinued intervention due to Tuberculosis (n=1) of declined prior to surgery (n=1) versus none in the therapy arm

Outcome measures and effect size (include 95%CI and p-value if available):

Hba_1c %, mean (SD)

I: 6.2 (0.7)

C: 7.7 (0.7)

Diabetes remission (i.e. Hba_1c <6.5%, without using any antidiabetic medication), n/N (%)

I: 5/8 (62.5%)

C: 0/10 (0%)

Fasting glucose level, mg/dL mean (SD)

I: 124 (20.6)

C: 170 (38.7)

Complications

No data available

Quality of life

No information.

%Weight loss

I: 25.5% (SD 5.56)

C: 4.88% (SD 5.53)

Author’s conclusion

In conclusion, our research suggests that there is a remarkable phenotypic improvement after metabolic surgery which occurs simultaneously with gut microbiota changes. Nevertheless, gut microbiome changes alone cannot explain the benefcial metabolic health impact of RYGB. Other mechanisms such as diet, hormonal changes, bile acids metabolism, and physical activity need to be further explored in this equation in order to better explain the metabolic improvement of T2D patients with mild obesity after RYGB.

Ikramuddin, 2013, 2015, 2016 and 2018

Subgroup analyses: Chong, 2017 comparing Taiwanese with American patients.

Type of study: international multicenter RCT

Setting and country: Four academic teaching hospitals in the U.S. and Taiwan

Funding and conflicts of interest:

The Diabetes Surgery Study (DSS) was supported by Covidien, Mansfield, MA. Covidien

provided funds for these five clinical locations: University of Minnesota, Minneapolis, MN, USA; Mayo Clinic, Rochester, MN, USA; Columbia University, New York City, NY, USA; National Taiwan University Hospital,

Taipei, Taiwan; Min-Sheng General Hospital, Taoyuan, Taiwan. This publication was supported in part by the

National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1 TR000040, formerly the National Center for Research Resources, Grant Number UL1 RR024156 to Columbia

University.

Dr Ikramuddin serves as an advisory board member for Novo Nordisk, USGI, and Medica, consults for Metamodix, and receives grant support from Medtronic, ReShape Medical, and institutional

support from Enteromedics. Dr Korner reported

that she has received institutional grant support

from Medtronic and the National Institutes of

Health (NIH), serves on the Scientific Advisory

Board of Digma Medical, and had served on the

speaker’s bureau for Takeda. Ms Thomas reports

that she received institutional grant support from Medtronic and the NIH. Dr Connett reported that

he has received institutional grant support from Medtronic and the NIH, travel expenses and personal support from the US Food and Drug

Administration advisory panel on pulmonary drugs, salary support from Medtronic for the Diabetes

Inclusion criteria:

age 30-67, a BMI of 30.0-39.9 kg/

m2, under a doctor's care for type 2 diabetes for at least 6 months prior to recruitment; a HbA1c ≥ 8.0% at the time of entry;

and a serum C-peptide level > 1.0 ng/ml 90 minutes after a liquid mixed meal of Ensure ®

(250 calories, 6 g fat/40 g carbohydrate/9 g protein).

Exclusion criteria: -

N total at baseline:

Intervention: 60

Control: 60

Subgroup (Chong, 2017)

Intervention: 36

Control: 35

Important prognostic factors²:

Age, mean (95% CI)

I: 49 (47 to 52)

C: 49 (47 to 51)

Sex:

I: 63% female

C: 57% female

BMI, mean (95% CI)

I: 34.9 (34.2 to 35.7)

C: 34.3 (33.5 to 35.1)

BMI 30.0-34.9 kg/m2

I: 60%

C: 58%

HbA1c (%), mean (95% CI)

I: 9.6 (9.4 to 9.9)

C: 9.6 (9.3 to 9.9)

Fasting Glucose (mg/dL), mean (95% CI)

I: 222 (203 to 241)

C: 207 (193 to 222)

Taking Insulin

I: 62%

C: 43%

Taking Other Glycemic Medicines

I: 87%

C: 95%

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

Participants randomized to the RYGB group were placed on a low calorie diet with meal replacements 2 weeks prior to the operation. Staff surgeons with extensive experience (> 300 cases) performed the RYGB. The laparoscopic RYGB technique was standardized across all sites and was performed with construction of a 20 ml lesser curvature gastric pouch, a 100 cm biliopancreatic limb, and an antecolic 150 cm Roux limb

with closure of all mesenteric defects.

Describe control (treatment/procedure/test):

Lifestyle/ Intensive Medical Management consisted of two components - lifestyle modification designed to produce maximum achievable weight loss, and medications to control glycemia and cardiovascular

disease risk factors while facilitating weight loss. Only U.S. Food and Drug Administration approved

medications were used.

Length of follow-up:

5 years (Ikramuddin, 2018)

Loss-to-follow-up:

Follow-up data available intervention:

57 In year 1 - 3 Lost to follow-up before 4 mo

56 In year 2

55 In year 3

54 In year 4

55 In year 5

Control:

56 In year 1 - 1 Died (pancreatic cancer), 3 Lost to follow-up before 4 mo

54 In year 2

44 In year 3

42 In year 4

43 In year 5

Outcome measures and effect size (include 95%CI and p-value if available):

Weight loss

Mean weight loss

1 year

I: 26.1% (95% CI 23.8 to 28.4)

C: 7.8% (95% CI 5.5 to 10.1)

5 year

I: 21.8%( 95% CI 19.5 to 24.1)

C: 9.6% (95% CI 7.2 tp 12.0)

Morbidity/ complications

Serious adverse events

1 year

I: 22 (4 perioperative complications and 6 late postoperative complications)

C: 15

DM2 control

HbA1c <6%

1 year

I: 45% (95% CI 26 to 65)

C: 5% (95% CI 2 to 16)

5 year

I: 11% (95% CI 4 to 26)

C: 3% (95% CI 0 to 13)

HbA1c %

1 year

I: 6.3 (6.1 to 6.5)

C: 7.8 (7.4 to 8.2)

5 year

I: 7.1% (95% CI 6.7%-7.5%)

C: 8.7% (95% CI 8.3%-9.1%)

Full diabetes remission (HbA1c < 6.0% and no use of antihyperglycemic medication

2 year

I: 16% (95% CI 7 to 33)

C: 0% (95% CI 0 to 7)

5 year

I: 7% (95% CI 2 to 19)

C: 0% (95% CI 0 to 8)

Fasting Glucose

Mg/ dL, mean

1 year

I: 111 (95% CI 97 to 125)

C: 153 (95% CI 138 to 167)

5 year

I: 132 (95% CI 117 to 146)

C: 168 (95% CI 152 to 183)

 <100 mg/dL

1 year

I: 44% (95% CI 28 to 62)

C: 11% (95% CI 5 to 24)

5 year

I: 25% (95% CI 13 to 43)

C: 4% (95% CI 1 to 15)

Using Insulin

1 year

I: 18% (95% CI 9 to 30)

C: 43% (95% CI 30 to 57)

5 year

I: 15% (95% CI 6 to 27)

C: 37% (95% CI 23 to 53)

Using Noninsulin Diabetes Medication

1 year

I: 35% (95% CI 23 to 49)

C: 98% (95% CI 90 to 100)

5 year

I: 42% (95% CI 29 to 56)

C: 88% (95% CI 75 to 96)

Mortality

I: 0

C: 0

Quality of life

Not reported

Life expectancy

Not reported

Author’s conclusion

In extended follow-up of obese adults with type 2 diabetes

randomized to adding gastric bypass compared with lifestyle and intensive medical

management alone, there remained a significantly better composite triple end point in the surgical group at 5 years. However, because the effect size diminished over 5 years, further follow-up is needed to understand the durability of the improvement.

Liang, 2013

Type of study: RCT

Setting and country: the Southwest Hospital of Third Military Medical University in

Chongqing, China

Funding and conflicts of interest: The study was supported by research grants from the National Natural Science Foundation of China (Grant No.:

30670838).

The authors declare that they have no conflict of interest.

Inclusion criteria: 1)

obesity (body mass index (BMI) > 28 kg/m2) in accordance

with the WHO Asia-Pacific classification for obesity; (2)

T2DM with hypertension of 5–10 years with hypertension

defined as systolic blood pressure (SBP) ≥140 mmHg and/or diastolic (DBP) ≥ 90 mmHg as per 1999 WHO/ISH criteria; (3) insulin therapy in combination with oral administration of

drugs for 12 months; (4) glycated hemoglobin (HbA1c) > 7%; (5) age: 30–60 years; (6) seronegative for antibodies against

insulin, islet cells and glutamic acid decarboxylase (GAD); (7)

C-peptide level ≥0.3 mg/L.

Exclusion criteria: (1)

people without diabetes; (2) type 1 diabetes mellitus,

presence of autoimmune diabetes indicated by antibodies

to insulin, islet cells, and GAD, and gestational diabetes; (3)

patients with heart, liver, or renal function impairment; (4)

presence of severe infections or cerebrovascular disease; (5)

fasting serum insulin was less than one-third of the normal value; (6) diabetes of more than 10 years duration; (7) age > 60 years or <30 years.

N total at baseline:

108 of whom 101 patients completed the trial:

Intervention: 31

Control1: 36

Control2: 34

Important prognostic factors²:

Age ± SD:

I: 50.81 SD 5.44

C1: 51.75 SD 6.7

C2: 50.94 SD 5.89

Sex M/F:

I: 22/ 9

C1: 24/ 12

C2: 24/10

BMI:

I: 30.48 SD 0.94

C1: 30.34 SD 1.96

C2: 30.28 SD 1.44

Course of T2DM (years)

I: 7.39 SD 1.69

C1: 7.24 SD 1.61

C2: 7.17 SD 1.80

HbA1c (%)

I: 10.47 SD 1.17

C1: 10.88 SD 1.40

C2: 10.52 SD 1.49

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

RYGB surgery using a

standard 5-port laparoscopic technique, the greater and lesser

curvatures of the stomach were separated, the gastric cavity closed with a disposable closure device, and a gastric pouch

created that was completely separated from the gastric

remnant and anastomosed to the jejunum. An entero–entero anastomosis was created between the pancreatobiliary limb

and alimentary limb 100 cm distally from the gastrojejunostomy.

Describe control (treatment/procedure/test):

C1: Usual care

C2: Usual care plus Exenatide treatment.

Exenatide was given 1 h before breakfast or dinner. Patients were injected with 0.5 mg Exenatide subcutaneously twice

daily for 1 month, then increased to 1.0 mg twice daily if tolerated.

Length of follow-up: 1 year

Loss-to-follow-up:

A total of 108 patients were included and 101 patients

successfully completed the trial (retention rate, 94%) and

follow-up compliance was 100%. No further information was provided.

Outcome measures and effect size (include 95%CI and p-value if available):

Weight loss

BMI at 1 year

I: 24.51 SD 0.91

C1: 30.38 SD 1.66

C2: 26.84 SD 1.21

Morbidity/ complications

Not reported

DM2 control

HbA1c (%)

I: 5.98 SD 0.30

C1: 8.14 SD 0.27

C2: 7.10 SD 0.26

Mortality

Not reported

Quality of life

Not reported

Life expectancy

Not reported

Author’s conclusion

RYGB surgery improves a number of parameters including cardiovascular function in obese hypertensive people with T2DM. This is likely to be due to, at least in part, an improvement in the abnormal metabolic panel and to reduced inflammation.

Parikh, 2015 (6 months follow-up)

Horwitz 2016 (3 years follow-up)

Horwitz, 2020 (5 years follow-up)

Type of study: pilot RCT, after 6 months patients were allowed to cross-over

Setting and country: New York City Health and Hospitals Corporation, USA

Funding and conflicts of interest: the study was supported by grant number K12HS019473 from the Agency for Healthcare Research and Quality and by grant number K12HS019473 from the Agency for Healthcare Research and Quality.

The authors declare there are no conflicts of interest.

Inclusion criteria:

patients with T2DM and BMI 30–35

who were otherwise eligible for bariatric surgery by NIH criteria, specifically: (1)

overweight for at least 5 years, (2) failure to lose weight with non-surgical means, (3)

absence of medical or psychological contraindications, (4) patient understanding of the procedure and its risks, and (5) strong motivation to comply with the post-surgical regimen.

Exclusion criteria: Patients were excluded if they were deemed unable to comply with the study protocol (either

self-selected or by indicating during screening that s/he could not complete all requested

tasks), participation in other obesity- or diabetes-related clinical trials, or diagnosis of

cognitive dysfunction or significant psychiatric comorbidity.

N total at baseline:

Intervention: 29

Control: 28*

*after 6 months 10 patients in the control group crossed-over

Important prognostic factors²:

Age ± SD:

I: 46.8 (8.1)

C: 53.9 (8.4)

Sex:

I: 21% M

C: 21% M

BMI

I: 32.8 (1.7)

C: 32.4 (1.8)

HbA1c

I: 7.7 (1.4)

C: 7.9 (1.3)

Requiring insulin

I: 34%

C: 39%

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Patients randomized to surgery underwent bypass, band or sleeve gastrectomy based on patient preference (drawing upon information learned in the monthly bariatric surgery information seminar and during the surgeon consultation). All patients underwent thorough evaluation by a surgeon, internist, nutritionist, and psychologist, and then completed a liquid protein diet for two weeks prior to surgery to decrease hepatomegaly.

Type of surgery selected:

None n=1

LAGB n=5

LSG n=16

RYGB n=7

Describe control (treatment/procedure/test):

The Intensive Medical Weight Management protocol was based on successful models of lifestyle counseling previously

published in the medical literature. These trials utilized intensive lifestyle interventions, including frequent group and individual sessions focusing on nutrition and physical activity counseling. MWM sessions were led by a bilingual weight loss clinician with an expertise in diabetes

education. Sessions were held weekly for the first month and then biweekly. In these 30-minute sessions, the clinician offered culturally tailored, patient-specific counseling on diet,

physical activity, self-monitoring, and goal setting. The visits included a review of home glucose data and adjustment of diabetes medications. In addition, participants were provided

with pedometers to track their progress, with a goal of 150 min/week of low-impact physical activity by 6 months.

Length of follow-up:

6 months, 3 years, 5 years

Loss-to-follow-up:

6 months

Intervention:

9 (31%)

8 participants withdrew from surgery group, 1 patient without 6 month data available.

A total of 20 patients were analyzed

Control:

4 (14%)

3 did not complete required number of visits, 1 patient without 6 month data available.

A total of 24 patients were analyzed

3 years

n = 44 patients with 3 year data

per protocol analyses

I: 30

C: 14

5 years

n = 43 patients with 5 year data

per protocol analyses

I: 29

C: 14

Outcome measures and effect size (include 95%CI and p-value if available):

6 months follow-up

Weight loss

%EWL

I: 60.0% SD 21.1

C: 7.4% SD 12.6

BMI

I: 25.9 SD 2.5

C: 31.4 SD 2.6

Morbidity/ complications

I: 2 (there was one readmission within 30 days for dehydration (resolved with

intravenous fluids and anti-emetics) and there was one late readmission (>30 days) for a trocar site abscess (resolved with percutaneous drainage and antibiotics).

C: 0

DM2 control

Diabetes Remission defined as as no longer meeting the American Diabetes Association criteria for T2DM, without the use of diabetes medications.

I: 65% (n=13)

C: 0%

HbA1c%

I: 6.2 SD 0.9

C: 7.8 SD 1.7

Fasting glucose

I: 99.5 SD 28.0

C: 156.9 SD 91.3

Requiring T2DM meds

I: 20% (n=4)

C: 88% (n=21)

Mortality

I: 0

C: 0

Quality of life

Not reported

Life expectancy

Not reported

3 years follow-up

Hba_1c %, mean (SD)

I: 6.91 (not reported)

C: 8.37 (not reported)

Remission: no longer meeting the ADA criteria, without the use of T2D medications

I: 19/30 (63%)

C: 0.14 (0%)

Complications intervention group

- No mortalities

-  No life-threatening complications

-  No 30-day reoperation

-  4 patients readmissions > 30 days

-  1 patient cholecystectomy

Complications control group

- No complications.

% Weight loss

I: 26.6%

C: 2.8%

% Excess weight loss

I: 52.9%

C: 8.7%

5 years follow-up

Hba_1c %, mean (SD)

I: 6.93 (1.37) N=27

C: 8.26 (1.8) N=14

T2D remission, n/N (%)

I: 11/29 (38%)

C: 0/14 (0%)

Medication (diabetic)

Metformin

I: 8

C: 2

Insulin

I: 9

C: 5

Other

I: 10

C: 5

% Weight loss

I: 21.4% (SD 9.4)

C: 10.3% (SD 8.1)

Complications

Mortalities, n/N (%)

I: 0/29 (0%)

C: 0/14 (0%)

Diabetic retinopathy, n/N (%)

I: 0/29 (0%)

C: 4/14 (29%)

Peripheral neuropathy, n/N (%)

I: 0/29 (0%)

C: 6/14 (43%)

Readmission or operation, n/N (%)

I: 11/29 (38%)

C: 10/14 (71%)Diabetes-related cardiovascular complications, n/N (%)

I: 0/29 (0%)

C: 2/14 (14%)

Quality of life

No information.

Author’s conclusion

Surgery was very effective short-term in patients with T2DM and BMI 30–35.

Baseline sRAGE may predict patients most likely to benefit from surgery. These findings need to be confirmed with larger studies.

Longer-term follow-up beyond 6 months confirmed that metabolic surgery was very effective (63% remission) in T2D remission in patients with T2D and BMI 30–35 at 3 years postintervention. T2D remission was not associated with %WL. However, higher baseline sRAGE predicted satisfactory outcomes with surgery. Larger-scale randomly assigned trials are needed in this patient population.

Azevedo, 2018

Type of study: RCT

Setting and country: Patients’ selection and clinical treatment were conducted at InCor, Universidade de Sao Paulo. Surgical procedures were performed

at Hospital Israelita Albert Einstein in São Paulo, Brazil.

Funding and conflicts of interest:

Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e

Tecnológico (CNPq).

The authors declare that they have no conflict of interest.

Inclusion criteria:

Inclusion criteria were ≤ 65 years old, male, T2D for > 2 and <10 years, body mass index (BMI) > 28 and < 35 kg/m2, waist

circumference > 102 cm, and glycated hemoglobin (HbA1c) level > 8% despite standard therapy provided by Brazilian health system (lifestyle management (dietary support and exercise

advice) plus metformin, sulfonylurea, and/or insulin).

Exclusion criteria:

C-peptide levels <1.5 ng/mL, positivity for the autoantibodies anti-GAD or ICA, active cancer, relevant acute or chronic infections, alcohol or drug abuse, or current smoking.

N total at baseline:

Intervention: 10

Control: 10

Important prognostic factors²:

Age ± SD:

I: 45 SD 10

C: 56 SD 7

T2DM duration, mean ± SD

I: 7.5 SD 2.0

C: 8.5 SD 3.2

BMI, mean ± SD

I: 33.4 SD 2.6

C: 30.3 SD 2.1

Groups comparable at baseline? No

Describe intervention (treatment/procedure/test):

Sleeve gastrectomy with transit bipartition

Describe control (treatment/procedure/test):

Standard medical therapy

Length of follow-up: 24 months

Loss-to-follow-up:

None

Outcome measures and effect size (include 95%CI and p-value if available):

Weight loss

Not reported

Morbidity/ complications

I: One patient developed cholelithiasis after 6 months and underwent elective cholecystectomy, and one patient presented transient anemia and hypoalbuminemia that resolved after 3 months of treatment.

C: not reported

DM2 control

HbA1c %

I: 5.5 SD 1.1

C: 8.3 SD 1.1

Glucose (mg/dL)

I: 95 SD 25

C: 182 SD 81

Insulin and/or sulfonylureas medication

I: 0%

C: 100%

Metformin

I: 20%

C: 90%

Mortality

Not reported

Quality of life

Not reported

Life expectancy

Not reported

Author’s conclusion

Sleeve gastrectomy with transit bipartition is superior to standard medical therapy and was associated with a better metabolic and cardiovascular profile.

Schauer, 2012, 2014 and 2017 (subgroup analyses)

NB Schauer included patients with a BMI of 27 to 43. For the literature summary only results of subgroup analyses of patients with a BMI <35 were extracted.

Type of study: RCT

Setting and country: Cleveland Clinic, USA

Funding and conflicts of interest: Supported by a grant (EES IIS 19900) from Ethicon Endo-

Surgery, a grant (R01-DK089547) from the National Institutes of

Health, and LifeScan.

The authors declared several conflicts of interest such as involvement in the industry.

Inclusion criteria:

age of 20 to 60 years, a diagnosis of type 2 diabetes (glycated haemoglobin level, >7.0%), and a BMI of 27 to 43.

Exclusion criteria: if patients had undergone previous bariatric

surgery or other complex abdominal surgery or had poorly controlled medical or psychiatric disorders

N total at baseline:

BMI<35

Intervention GB: 14 (28%)

Intervention SG: 18 (36%)

Control: 19 (38%)

Important prognostic factors²:

Not described for subgroup BMI<35.

Groups comparable at baseline? Unclear

Describe intervention (treatment/procedure/test):

Intervention 1 Gastic bypass

Medical therapy plus gastric bypass consisted of the creation of a 15-to-

20-ml gastric pouch, a 150-cm Roux limb, and a

50-cm biliopancreatic limb.

Intervention 2 Sleeve gastrectomy

Medical therapy plus sleeve gastrectomy involved

a gastric-volume reduction of 75 to 80% by resecting

the stomach alongside a 30-French endoscope

beginning 3 cm from the pylorus and ending at

the angle of His

Describe control (treatment/procedure/test):

Medical therapy

All patients received intensive medical therapy, as defined by American Diabetes Association (ADA)

guidelines, including lifestyle counseling, weight

management, frequent home glucose monitoring,

and the use of newer drug therapies (e.g., incretin

analogues) approved by the Food and Drug Administration

(FDA).

Length of follow-up: 5 years

Loss-to-follow-up:

Not described for subgroup BMI<35.

Incomplete outcome data

I: 0

C: 2

Outcome measures and effect size (include 95%CI and p-value if available):

Weight loss

Not reported

Morbidity/ complications

Not reported

DM2 control

Glycated Hemoglobin level (HbA1c%)

1 year

I: mean 6.6 (SD 0.9) ( n=31)

C: 7.9 SD 1.8) (n=18)

2 years

I: 6.8 SD 1.1) (n=31)

C: 8.0 (SD 1.8) (n=18)

3 years

I: mean 7.1 (SD 6.7) (n=31)

C: mean 8.1 (SD 7.8) (n=18)

5 years

I: mean 7.3 (SD 7.1) (n=32)

C: mean 8.8 (SD 8.0) (n=17)

Mortality

Not reported

Quality of life

Not reported

Life expectancy

Not reported

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/ unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/ unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/ unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/ unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/ unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/ unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/ unclear)

Cohen (2020)

Using a computer-generated, centrally concealed, and sex-stratified 1:1 randomization sequence, we assigned 100 eligible patients to best medical treatment or RYGB

Unclear

No information regarding allocation concealment provided.

Likely

Likely

Unclear

Unlikely

Unlikely

Unlikely

Lau (2021)

Consequently, we included 20 participants who were randomly assigned to one of the two study arms, with a 1:1 ratio, using a computer-generated randomisation procedure, to receive either RYGB or standard medical therapy

Unlikely

Likely

Likely

Likely

Unlikely

Unlikely

Likely

Ikramuddin, 2013, 2015, 2016 and 2018

Participants were randomized with equal probability to control or intervention. The randomization schedule used permutated blocks of random length within each site, so that each site would have nearly equal proportions in each arm.

Likely, randomization assignment was

unblinded.

Likely

Likely

Unlikely

Unlikely

Unlikely

Unlikely

Liang, 2013

Patients were randomized into three groups in a 1:1:1 ratio with the use of a computerized system for generating random numbers.

Unlikely

Likely

Likely

Unclear

Unlikely

Unlikely

Likely

Parikh, 2014

Horwitz (2016) / (2020)

Patients were randomized by RAs calling a central phone number to receive allocation; the allocation sequence was generated in advance and stratified to ensure balance of patients with BMI 30–35 in each of the arms.

Unlikely

Likely

Likely

Likely

Unlikely

Likely

Likely

Azevedo, 2018

Not described

Unclear

Likely

Likely

Likely

Unlikely

Unlikely

Unlikely

Schauer, 2012, 2014 and 2017

Using a block-randomization method with a 1:1:1 ratio, 150 patients were assigned to undergo intensive medical therapy alone or intensive medical therapy plus either Roux-en-Y gastric bypass or sleeve gastrectomy, with stratification according to the patients’ use of insulin at baseline.

Unlikely

Likely

Likely

Likely

Unlikely

Unlikely

Unclear for the subgroup