Obesity is a risk factor for diabetes, cardiovascular disease events, cancer and overall mortality. Weight loss may protect against these conditions, but robust evidence for this has been lacking. The Swedish Obese Subjects (SOS) study is the first long-term, prospective, controlled trial to provide information on the effects of bariatric surgery on the incidence of these objective endpoints. The SOS study involved 2010 obese subjects who underwent bariatric surgery [gastric bypass (13%), banding (19%) and vertical banded gastroplasty (68%)] and 2037 contemporaneously matched obese control subjects receiving usual care. The age of participants was 37-60 years and body mass index (BMI) was ≥34 kg m(-2) in men and ≥38 kg m(-2) in women. Here, we review the key SOS study results published between 2004 and 2012. Follow-up periods varied from 10 to 20 years in different reports. The mean changes in body weight after 2, 10, 15 and 20 years were -23%, -17%, -16% and -18% in the surgery group and 0%, 1%, -1% and -1% in the control group respectively. Compared with usual care, bariatric surgery was associated with a long-term reduction in overall mortality (primary endpoint) [adjusted hazard ratio (HR) = 0.71, 95% confidence interval (CI) 0.54-0.92; P = 0.01] and decreased incidences of diabetes (adjusted HR=0.17; P < 0.001), myocardial infarction (adjusted HR = 0.71; P = 0.02), stroke (adjusted HR=0.66; P = 0.008) and cancer (women: adjusted HR = 0.58; P = 0.0008; men: n.s.]. The diabetes remission rate was increased severalfold at 2 years [adjusted odds ratio (OR) = 8.42; P < 0.001] and 10 years (adjusted OR = 3.45; P < 0.001). Whereas high insulin and/or high glucose at baseline predicted favourable treatment effects, high baseline BMI did not, indicating that current selection criteria for bariatric surgery need to be revised.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.12012

Review of the key results from the Swedish Obese Subjects (SOS) trial – a prospective controlled intervention study of bariatric surgery

The medical effects of modest weight reduction (approximately 10% or less) in patients with obesity-associated medical complications were reviewed. The National Library of Medicine MEDLINE database and the Derwent RINGDOC database were searched to identify English language studies that examined the effects of weight loss in obese patients with serious medical complications commonly associated with obesity (non-insulin dependent diabetes mellitus (NIDDM or type II), hypertension, hyperlipidemia, hypercholesterolemia, and cardiovascular disease). Studies in which patients experienced approximately 10% or less weight reduction were selected for review. Studies indicated that, for obese patients with NIDDM, hypertension or hyperlipidemia, modest weight reduction appeared to improve glycemic control, reduce blood pressure, and reduce cholesterol levels, respectively. Modest weight reduction also appeared to increase longevity in obese individuals. In conclusion, a large proportion of obese individuals with NIDDM, hypertension, and hyperlipidemia experienced positive health benefits with modest weight loss. For patients who are unable to attain and maintain substantial weight reduction, modest weight loss should be recommended; even a small amount of weight loss appears to benefit a substantial subset of obese patients.

Beneficial health effects of modest weight loss.

BACKGROUND Weight loss protects against type 2 diabetes but is hard to maintain with behavioral modification alone. In an analysis of data from a nonrandomized, prospective, controlled study, we examined the effects of bariatric surgery on the prevention of type 2 diabetes. METHODS In this analysis, we included 1658 patients who underwent bariatric surgery and 1771 obese matched controls (with matching performed on a group, rather than individual, level). None of the participants had diabetes at baseline. Patients in the bariatric-surgery cohort underwent banding (19%), vertical banded gastroplasty (69%), or gastric bypass (12%); nonrandomized, matched, prospective controls received usual care. Participants were 37 to 60 years of age, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was 34 or more in men and 38 or more in women. This analysis focused on the rate of incident type 2 diabetes, which was a prespecified secondary end point in the main study. At the time of this analysis (January 1, 2012), participants had been followed for up to 15 years. Despite matching, some baseline characteristics differed significantly between the groups; the baseline body weight was higher and risk factors were more pronounced in the bariatric-surgery group than in the control group. At 15 years, 36.2% of the original participants had dropped out of the study, and 30.9% had not yet reached the time for their 15-year follow-up examination. RESULTS During the follow-up period, type 2 diabetes developed in 392 participants in the control group and in 110 in the bariatric-surgery group, corresponding to incidence rates of 28.4 cases per 1000 person-years and 6.8 cases per 1000 person-years, respectively (adjusted hazard ratio with bariatric surgery, 0.17; 95% confidence interval, 0.13 to 0.21; P<0.001). The effect of bariatric surgery was influenced by the presence or absence of impaired fasting glucose (P = 0.002 for the interaction) but not by BMI (P = 0.54). Sensitivity analyses, including end-point imputations, did not change the overall conclusions. The postoperative mortality was 0.2%, and 2.8% of patients who underwent bariatric surgery required reoperation within 90 days owing to complications. CONCLUSIONS Bariatric surgery appears to be markedly more efficient than usual care in the prevention of type 2 diabetes in obese persons. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01479452.)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1112082

Bariatric Surgery and Prevention of Type 2 Diabetes in Swedish Obese Subjects

OBJECTIVE To investigate the efficacy and tolerability of empagliflozin as an add-on to metformin therapy in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS Patients with HbA1c levels of ≥7% to ≤ 10% (≥53 to ≤86 mmol/mol) while receiving metformin (≥1,500 mg/day) were randomized and treated with once-daily treatment with empagliflozin 10 mg ( n = 217), empagliflozin 25 mg ( n = 213), or placebo ( n = 207) for 24 weeks. The primary end point was the change in HbA1c level from baseline at week 24. Key secondary end points were changes from baseline in weight and mean daily glucose (MDG) at week 24.

RESULTS At week 24, adjusted mean (SE) changes from baseline in HbA1c were −0.13% (0.05)% (−1.4 [0.5] mmol/mol) with placebo, −0.70% (0.05)% (−7.7 [0.5] mmol/mol) with empagliflozin 10 mg, and −0.77% (0.05)% (−8.4 [0.5] mmol/mol) with empagliflozin 25 mg (both P < 0.001). Empagliflozin significantly reduced MDG level and systolic and diastolic blood pressure (BP) versus placebo. Adjusted mean (SE) changes from baseline in weight were −0.45 kg (0.17 kg) with placebo, −2.08 kg (0.17 kg) with empagliflozin 10 mg, and −2.46 kg (0.17 kg) with empagliflozin 25 mg (both P < 0.001). Adverse events (AEs) were similar across groups (placebo 58.7%; empagliflozin 49.5–57.1%). Confirmed hypoglycemic AEs were reported in 0.5%, 1.8%, and 1.4% of patients receiving placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. Events consistent with urinary tract infections were reported in 4.9%, 5.1%, and 5.6% of patients, and events consistent with genital infections were reported in 0%, 3.7%, and 4.7% of patients, respectively.

CONCLUSIONS Empagliflozin 10 and 25 mg for 24 weeks as add-on to metformin therapy significantly improved glycemic control, weight, and BP, and were well-tolerated.

https://care.diabetesjournals.org/content/diacare/37/6/1650.full.pdf

Empagliflozin as Add-On to Metformin in Patients With Type 2 Diabetes: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Trial

Background
The high prevalence of obesity (24% of the adult population) and its adverse effects on health call for effective prevention and treatment.

The Prevention and Treatment of Obesity

Interdisziplinare Leitlinie der Qualitat S3 zur „Pravention und Therapie der Adipositas“ - der Deutschen Adipositas-Gesellschaft e.V.; der Deutschen Diabetes Gesellschaft; der Deutschen Gesellschaft fur Ernahrung e.V.; der Deutschen Gesellschaft fur Ernahrungsmedizin e.V. Version 2.0 (April 2014); AWMF-Register Nr. 050-001

Interdisziplinäre Leitlinie der Qualität S3 zur „Prävention und Therapie der Adipositas“

Background
The young field of obesity surgery (bariatric surgery) in Germany expands as a consequence of the rapid increase of overweight and obesity. New surgical methods, minimal access techniques, and the enormous increase of scientific studies and evidence, all contribute to the success of bariatric surgery, which is the only realistic chance of permanent weight loss and regression of secondary diseases in many cases.

Evidence-based German guidelines for surgery for obesity.

Ergebnisse: Die Adipositas (Body-mass-Index [BMI] ≥ 30 kg/m) wird als chronische Krankheit charakterisiert. Der Prävention kommt eine besondere Bedeutung zu. Zur Gewichtsabnahme bei Adipositas und zur Stabilisierung eines reduzierten Gewichts wird eine Kost mit einem Energiedefizit von 500 kcal/d und geringer Energiedichte empfohlen. Die Relation der Makronährstoffe ist für die Gewichtsabnahme zweitrangig. Übersteigt der BMI 30 kg/m, können zeitlich begrenzt Formulaprodukte eingesetzt werden. Vermehrte Bewegung im Alltag und in der Freizeit begünstigt die Gewichtsabnahme und verbessert Risikofaktoren und Adipositas-assoziierte Krankheiten. Eine Verhaltensmodifikation beziehungsweise Verhaltenstherapie unterstützt eine Änderung der Ernährung und Bewegung im Alltag. Bezüglich einer Lebensstiländerung gibt es keine wissenschaftliche Evidenz für eine bestimmte Abfolge der Maßnahmen. Empfehlenswert sind Gewichtsreduktionsprogramme, deren Wirksamkeit wissenschaftlich evaluiert ist. Chirurgische Interventionen sind im Vergleich zu konservativen Maßnahmen hinsichtlich der Reduktion des Körperfetts, Besserung von Adipositas-assoziierten Krankheiten und Senkung des Sterblichkeitsrisikos effektiver. Innerhalb von ein bis zwei Jahren ist eine Gewichtsabnahme von circa 4 bis 6 kg unter Ernährungstherapie, von circa 2 bis 3 kg unter Bewegungstherapie und von 20 bis 40 kg nach einer bariatrischen Operation in kontrollierten Studien festzustellen.

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Prävention und Therapie der Adipositas

Begleitund Folgeerkrankungen ! Die wichtigsten Begleitund Folgeerkrankungen der Adipositas sind im Anhang (s.Praxistools, l" Tab.2) aufgelistet. Ein besonders enger Zusammenhang besteht zwischen BMI und Diabetesrisiko. Adipositas geht zudem mit einer Verkurzung der Lebenserwartung einher. Ab einem BMI von 27 bis 30 nimmt die Mortalitat an Herz-Kreislauf-Erkrankungen und Karzinomen zu. Bei adiposen Schwangeren treten Schwierigkeiten bei der Geburt gehauft auf. Praxistool (s. Anhang)

/pdf/adipositas-und-diabetes-mellitus-2a8s5x9m18.pdf

Alfred Wirth

Papers

The Prevention and Treatment of Obesity

Interdisziplinäre Leitlinie der Qualität S3 zur „Prävention und Therapie der Adipositas“

Evidence-based German guidelines for surgery for obesity.

Prävention und Therapie der Adipositas

Adipositas und Diabetes mellitus