Medications for the treatment of obesity.

After several years with no real therapeutic alternatives, the management of obesity is entering a new era with the development of new surgical and endoscopic bariatric techniques, digital therapeutics and the arrival of new classes of drugs. New medication treatments aim to reduce food intake, targeting the hypothalamic regulation of food intake and satiety. The mechanism of their action remains poorly understood but, combines weight reduction and amelioration of cardiometabolic risk factors with a favorable benefit-risk balance and known side effects, mainly digestive. The future will tell us how these drugs will find their place in the management of this chronic disease that is obesity.

Evolution of the nutritional status of COVID-19 critically-ill patients: A prospective observational study from ICU admission to three months after ICU discharge.

BACKGROUND & AIMS: Malnutrition following intensive care unit (ICU) stay is frequent and could be especially prominent in critically ill Coronavirus Disease 2019 (COVID-19) patients as they present prolonged inflammatory state and long length stay. We aimed to determine the prevalence of malnutrition in critically ill COVID-19 patients both at the acute and recovery phases of infection. METHODS: We conducted a prospective observational study including critically ill COVID-19 patients requiring invasive mechanical ventilation discharged alive from a medical ICU of a university hospital. We collected demographic, anthropometric and ICU stay data (SAPS2, recourse to organ support and daily energy intake). Nutritional status and nutritional support were collected at one month after ICU discharge (M1) by phone interview and at 3 months after ICU discharge (M3) during a specialized and dedicated consultation conducted by a dietitian. Malnutrition diagnosis was based on weight loss and body mass index (BMI) criteria following the Global Leadership Initiative on Malnutrition. Primary outcome was the prevalence of malnutrition at M3 and secondary outcomes were the evolution of nutritional status from ICU admission to M3 and factors associated with malnutrition at M3. RESULTS: From march 13th to may 15th, 2020, 38 patients were discharged alive from the ICU, median [IQR] age 66 [59-72] years, BMI 27.8 [25.5-30.7] kg/m2 and SAPS2 47 [35-55]. Thirty-three (86%) patients were followed up to M3. Prevalence of malnutrition increased during the ICU stay, from 18% at ICU admission to 79% at ICU discharge and then decreased to 71% at M1 and 53% at M3. Severe malnutrition prevailed at ICU discharge with a prevalence of 55% decreasing 32% at M3. At M3, the only factors associated with malnutrition in univariate analysis were the length of invasive mechanical ventilation and length of ICU stay (28 [18-44] vs. 13 [11-24] days, P = 0.011 and 32 [22-48] vs. 17 [11-21] days, P = 0.006, respectively), while no ICU preadmission and admission factors, nor energy and protein intakes distinguished the two groups. Only 35% of undernourished patients at M3 had benefited from a nutritional support. CONCLUSION: Malnutrition is frequent, protracted and probably underrecognized among critically ill Covid-19 patients requiring invasive mechanical ventilation with more than half patients still being undernourished three months after ICU discharge. A particular attention should be paid to the nutritional status of these patients not only during their ICU stay but also following ICU discharge.

Recommendations for nutritional care after bariatric surgery: Recommendations for best practice and SOFFCO-MM/AFERO/SFNCM/expert consensus.

Nutritional care after bariatric surgery is an issue of major importance, especially insofar as risk of deficiency has been extensively described in the literature. Subsequent to the deliberations carried out by a multidisciplinary working group, we are proposing a series of recommendations elaborated using the Delphi-HAS (official French health authority) method, which facilitates the drawing up of best practice and consensus recommendations based on the data of the literature and on expert opinion. The recommendations in this paper pertain to dietary management and physical activity, multivitamin and trace element supplementation and the prevention and treatment of specific deficiencies in vitamins B1, B9, B12, D and calcium, iron, zinc, vitamins A, E and K, dumping syndrome and reactive hypoglycemia.

Population pharmacokinetics and dosing simulations of amoxicillin in obese adults receiving co-amoxiclav.

BACKGROUND: Pneumonia, skin and soft tissue infections are more frequent in obese patients and are most often treated by co-amoxiclav, using similar dosing regimens to those used for non-obese subjects. No data are available on amoxicillin pharmacokinetics among obese subjects receiving co-amoxiclav. MATERIALS AND METHODS: Prospective, single-centre, open-label, non-randomized, crossover pharmacokinetic trial having enrolled obese otherwise healthy adult subjects. A first dose of co-amoxiclav (amoxicillin/clavulanate 1000/200 mg) was infused IV over 30 min, followed by a second dose (1000/125 mg) administered orally, separated by a washout period of ≥24 h. We assayed concentrations of amoxicillin by a validated ultra HPLC-tandem MS technique. We estimated population pharmacokinetic parameters of amoxicillin by non-linear mixed-effect modelling using the SAEM algorithm developed by Monolix. RESULTS: Twenty-seven subjects were included in the IV study, with 24 included in the oral part of the study. Median body weight and BMI were 109.3 kg and 40.6 kg/m2, respectively. Amoxicillin pharmacokinetics were best described by a two-compartment model with first-order elimination. Mean values for clearance, central volume, intercompartmental clearance and peripheral volume were, respectively, 14.6 L/h, 9.0 L, 4.2 L/h and 6.4 L for amoxicillin. Oral bioavailability of amoxicillin was 79.7%. Amoxicillin Cmax after oral administration significantly reduced with weight (P = 0.013). Dosing simulations for amoxicillin predicted that most of the population will achieve the pharmacodynamic target of fT>MIC ≥40% with the regimen of co-amoxiclav 1000/200 mg (IV) or 1000/125 mg (oral) q8h for MICs titrated up to 0.5 mg/L (IV) and 1 mg/L (oral). CONCLUSIONS: Pharmacokinetic/pharmacodynamic goals for amoxicillin can be obtained in obese subjects.

Diagnostic of hepatic fibrosis with the XL probe of the Fibroscan versus biopsies in patients candidates to bariatric surgery.

BACKGROUND AND AIMS: The risks of the histological evaluation for metabolic liver disease in severe obese subjects led to the development of the Fibroscan® device. The main objective of our study is to evaluate the diagnostic performance of XL probe for the measurement of hepatic fibrosis compared to histological examination, in obese subjects operated from bariatric surgery. METHODS: We included patients free from chronic liver diseases. Liver measurement and controlled attenuation parameter (CAP) were carried out using the Fibroscan®. Liver biopsies were performed during bariatric surgery and evaluated by two pathologists. Correlation between vibration-controlled transient elastography (VCTE) and fibrosis stage was assessed using the Kendall correlation coefficient. Diagnosis performance was assessed using receiver-operating-characteristic curve analysis together with its 95% confidence interval. Cut-off value maximizing the Youden index was computed together with specificity, sensitivity, positive and negative predictive values. RESULTS: The average age and body mass index were 41 years and 43 kg/m2, respectively (n = 108). Forty-one percent of patients presented fibrosis on the histological results. The Kendall correlation coefficient between fibrosis stage and liver stiffness measurement (LSM) was κ = 0.33, p<10-5. ROC analysis for the detection of fibrosis indicated the following values: 0.70 [0.60-0.79] for F≥1, 0.83 [0.72-0.92] for F≥2, 0.90 [0.83-0.97] for F≥3. Optimal cut-offs maximizing the Youden index were 7.0 kPa for F≥1, 8.1 kPa for F≥2 and 8.7 kPa for F≥3. CONCLUSION: Fibroscan® appears to be reliable for detection of significant and severe fibrosis in severe obese patients such as candidates for bariatric surgery. CLINICAL TRIAL NUMBER: NCT03548597.

Bariatric surgery and the perioperative management of type 2 diabetes: Practical guidelines.

BACKGROUND: Metabolic surgery is now considered as a therapeutic option in type 2 diabetes (T2D). However, few data are available regarding perioperative management of T2D. OBJECTIVES: To assess current practice among bariatric teams regarding perioperative management of T2D in order to propose guidelines. METHODS: A two-round Delphi method using online surveys was employed among bariatric teams experts (surgeons, diabetologists, anesthetists, nutritionists): first round, 63 questions covering 6 topics (characteristics of experts/teams, characteristics of patients, operative technique, pre/postoperative management, diabetes remission); second round, 44 items needing clarification. They were discussed within national congress of corresponding learned societies. Consensus was defined as ≥66% agreement. RESULTS: A total of 170 experts participated. Experts favored gastric bypass to achieve remission (76.7%). Screening for retinopathy, cardiac ultrasound, and reaching an HbA1c<8% are required in the pre-operative period for 67%, 75.3% and 56.7% of experts, respectively. After surgery, insulin pump should not be stopped, basal insulin should be halved, and bolus insulin should be stopped except if severe hyperglycemia. DPP-IV inhibitors and metformin are preferred after surgery. Patients should be seen by a diabetologist within one month if on oral antidiabetic agents (71.8% of experts), 2 weeks if on injectable treatments (77.1% of experts), and immediately after surgery if on insulin pump (93.5% of experts). Long-term monitoring of HbA1c is necessary even if diabetes remission (100%). CONCLUSION: Rapid postoperative modifications of blood glucose require a close monitoring and a prompt adjustment of diabetes medications.

Multicentre cohort study of antihypertensive and lipid-lowering therapy cessation after bariatric surgery.

BACKGROUND: Few studies have assessed changes in antihypertensive and lipid-lowering therapy after bariatric surgery. The aim of this study was to assess the 6-year rates of continuation, discontinuation or initiation of antihypertensive and lipid-lowering therapy after bariatric surgery compared with those in a matched control group of obese patients. METHODS: This nationwide observational population-based cohort study used data extracted from the French national health insurance database. All patients undergoing gastric bypass or sleeve gastrectomy in France in 2009 were matched with control patients. Mixed-effect logistic regression models were used to analyse factors that influenced discontinuation or initiation of treatment over a 6-year interval. RESULTS: In 2009, 8199 patients underwent primary gastric bypass (55·2 per cent) or sleeve gastrectomy (44·8 per cent). After 6 years, the proportion of patients receiving antihypertensive and lipid-lowering therapy had decreased more in the bariatric group than in the control group (antihypertensives: -40·7 versus -11·7 per cent respectively; lipid-lowering therapy: -53·6 versus -20·2 per cent; both P < 0·001). Gastric bypass was the main predictive factor for discontinuation of therapy for hypertension (odds ratio (OR) 9·07, 95 per cent c.i. 7·72 to 10·65) and hyperlipidaemia (OR 11·91, 9·65 to 14·71). The proportion of patients not receiving treatment at baseline who were subsequently started on medication was lower after bariatric surgery than in controls for hypertension (5·6 versus 15·8 per cent respectively; P < 0·001) and hyperlipidaemia (2·2 versus 9·1 per cent; P < 0·001). Gastric bypass was the main protective factor for antihypertensives (OR 0·22, 0·18 to 0·26) and lipid-lowering medication (OR 0·12, 0·09 to 0·15). CONCLUSION: Bariatric surgery is associated with a good discontinuation of antihypertensive and lipid-lowering therapy, with gastric bypass being more effective than sleeve gastrectomy.

Long-term follow-up after bariatric surgery in a national cohort.

BACKGROUND: Lifelong medical follow-up is mandatory after bariatric surgery. The aim of this study was to assess the 5-year follow-up after bariatric surgery in a nationwide cohort of patients. METHODS: All adult obese patients who had undergone primary bariatric surgery in 2009 in France were included. Data were extracted from the French national health insurance database. Medical follow-up (medical visits, micronutrient supplementation and blood tests) during the first 5 years after bariatric surgery was assessed, and compared with national and international guidelines. RESULTS: Some 16 620 patients were included in the study. The percentage of patients with at least one reimbursement for micronutrient supplements decreased between the first and fifth years for iron (from 27.7 to 24.5 per cent; P < 0.001) and calcium (from 14·4 to 7·7 per cent; P < 0·001), but increased for vitamin D (from 33·1 to 34·7 per cent; P < 0·001). The percentage of patients with one or more visits to a surgeon decreased between the first and fifth years, from 87·1 to 29·6 per cent (P < 0·001); similar decreases were observed for visits to a nutritionist/endocrinologist (from 22·8 to 12·4 per cent; P < 0·001) or general practitioner (from 92·6 to 83·4 per cent; P < 0·001). The mean number of visits to a general practitioner was 7·0 and 6·1 in the first and the fifth years respectively. In multivariable analyses, male sex, younger age, absence of type 2 diabetes and poor 1-year follow-up were predictors of poor 5-year follow-up. CONCLUSION: Despite clear national and international guidelines, long-term follow-up after bariatric surgery is poor, especially for young men with poor early follow-up.

Should Sensory Impairment Be Considered in Frailty Assessment? A Study in the GAZEL Cohort.

OBJECTIVES: The assessment of sensory difficulties is sometimes included in the screening of frailty in ageing population. This study aimed to compare the prevalence of frailty and associated risk of adverse outcomes depending on whether sensory difficulties participated in the definition of frailty. DESIGN: Prospective cohort study - GAZEL cohort. SETTING: France. PARTICIPANTS: The 13,128 subjects who completed a questionnaire in 2012. MEASUREMENTS: According to the Strawbridge questionnaire, subjects were considered frail if they reported difficulties in two domains or more among physical, nutritive, cognitive and sensory domains. The risk of adverse health outcomes was assessed by using logistic regression models (hospitalisations, onset of difficulty in performing movements of everyday life) and multivariate Cox proportional hazards models (mortality). RESULTS: Mean age was 66.8 +/- 3.4 years and 73.8% were males. The prevalence of frailty varied from 4.4 to 14.2% depending on whether the sensory domain was excluded or included. During follow-up, 182 deaths (1.4%), 479 hospitalisations (3.6%) and 703 cases of new disability (8.0%) were observed. Both definitions of frailty predicted the onset of difficulties to perform everyday movements, with 2 to 3-fold increase in the risk. The inclusion of the sensory domain in the definition made frailty predictive of hospitalisations (Odds Ratio 1.31 [1.01-1.70]) but the association with mortality was only observed when sensory difficulties were ignored (Hazard Ratio 2.28 [1.32-3.92]). CONCLUSION: The inclusion of a sensory domain into a frailty screening instrument has a major impact in terms of prevalence and modifies the risk profile associated with frailty. In order to develop the use of frailty screening instruments in clinical practice, further researches will need to carefully evaluate the impact on risk prediction of the different domains involved.

Evolution of hypothalamic lipoma after Roux-en-Y gastric bypass.

Severe obesity is a common consequence of hypothalamic region diseases and their treatment. Only two previous case reports have described hypothalamic lipomas in children with obesity. We described a case of an adult with severe obesity associated with hypothalamic lipoma attached to the third ventricle floor who underwent Roux-en-Y gastric bypass. He lost 38 and 59 kg at 6 and 12 months after surgery, respectively. Weight loss after bariatric surgery was as expected in this patient with severe obesity. At 6 and 12 months, brain magnetic resonance imaging (MRI) showed stability in lipoma's size.

Risk of Dumping Syndrome after Sleeve Gastrectomy and Roux-en-Y Gastric Bypass: Early Results of a Multicentre Prospective Study.

Background. Bariatric surgery is an important field of surgery. An important complication of bariatric surgery is dumping syndrome (DS). Aims. To evaluate the incidence of DS in patients undergoing bariatric surgery. Methods. 541 patients included from 5 nutrition and bariatric centers in France underwent either LSG or LRYGB. They were evaluated at 1 month (M1) and 6 months (M6) postoperatively by an interview and completion of a dumping syndrome questionnaire. Results. 268 patients underwent LSG (Group A) and 273 underwent LRYGB. From the LRYGB patients 229 had mechanical gastrojejunoanal anastomosis with 30 mm linear stapler (Group B) and 44 had manual (hand sewn) 15 mm gastrojejunal anastomosis (Group C). Overall incidence of DS was 8.5% at M1 and M6. In LSG group (Group A), only 4 patients (1.49%) reported episodes of DS at M1 and 3 (1.12%) at M6. In Group B, 41 patients (17.90%) reported episodes of DS at M1 and 43 (18.78%) at M6. Group C experienced one case (2.27%) of DS at M1 and none (0%) at M6. Conclusions. Patients undergoing LRYGB, especially with larger gastrojejunal anastomosis, are more prone to developing DS following surgery than patients undergoing LSG or LRYGB with calibrated manual anastomosis.

Periodontopathogens antibodies and major adverse events following an acute myocardial infarction: results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI).

BACKGROUND: Periodontopathogens antibodies have been shown to be associated with primary myocardial events, but little is known regarding their impact on major adverse events after a prior acute myocardial infarction (AMI). The present prospective study evaluates the association between antibody levels of 4 periodontopathogens and the risk of all-cause death or non-fatal myocardial infarction (MI) at 1 year in 975 patients admitted for acute ST segment or non-ST segment elevation MI in French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI), a nationwide French survey. METHODS: Multiserotype ELISAs were performed to assess levels of IgG and IgA against Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Tannerella forsythia. RESULTS: Adjusted HRs indicate the lack of association between IgG-anti-Po. gingivalis levels (0.96 (0.78 to 1.18)), IgA-anti-Po. gingivalis levels (1.13 (0.90 to 1.42)) and the risk of all-cause death or non-fatal MI at 1 year. Additionally, no significant association was found between the occurence of an event at 1 year and immunoglobulins levels against the others periodontopathogens. CONCLUSIONS: The present data indicate that circulating levels of periodontopathogens antibodies are not associated with an increased risk of major adverse events in patients with a prior AMI. Studies dealing with bacterial and clinical data are needed to assess the role of oral health in comprehensive cardiac rehabilitation programmes.

Association between depression and anemia in otherwise healthy adults.

OBJECTIVE: It remains debated whether anemia is associated with depression, independently of physical health factors. We report a large-scale cross-sectional study examining this association in adults free of chronic disease and medication from the general population. METHOD: Hemoglobin levels were measured among 44 173 healthy participants [63% men; mean [standard deviation] age = 38.4 (11.1) years] from the 'Investigations Préventives et Cliniques' (IPC) cohort study. Depression was measured with the Questionnaire of Depression 2nd version, Abridged. Logistic regression analyses were performed to examine the association between anemia and depression, while adjusting for a wide range of sociodemographic characteristics and health-related factors (i.e., sex, age, living status, education level, occupational status, alcohol intake, smoking status, physical activity, and body mass index). RESULTS: Depressed participants were significantly more likely to have anemia compared to non-depressed participants, even after adjustment for sociodemographic and health-related variables [odds ratio = 1.36; 95% confidence interval = (1.18; 1.57)]. Anemia prevalence increased with depression severity, suggesting a dose-response relationship (P for trend <0.001). CONCLUSION: In healthy adults from the general population, we found a significant and robust association between depression and anemia. Further studies are needed to assess the longitudinal relationship between both conditions and determine the mechanisms underlying this association.

Association between current perceived stress and incident diabetes is dependent on occupational status: Evidence from the IPC cohort study.

AIM: The role of stress in the onset of type 2 diabetes is a widespread lay belief, yet observational studies have produced inconsistent results. This study aimed to test the hypothesis that the association between perceived stress and incident diabetes might depend on occupational status (OS). METHODS: The four-item Perceived Stress Scale (PSS-4) was completed at baseline by 22,567 participants in the labour force (16,193 men, 6374 women; mean age: 44.5±9.8 years) who had undergone two health checkups subsidized by the French national healthcare system. All subjects were free from diabetes at baseline, defined as a fasting blood glycaemia≥7mmol/L or the use of antidiabetic drugs. RESULTS: After a mean follow-up of 5.3±2.1 years, 527 participants (2.3%) had incident diabetes. After adjusting for sociodemographic, behavioural and biomedical risk factors as well as self-rated health, the association between baseline perceived stress and diabetes at follow-up was non-significant for the total study population. However, perceived stress was significantly associated with incident diabetes in participants of low OS [odds ratio (OR) for a five-point increment: 1.39; 95% confidence interval (CI): 1.02-1.90]. In contrast, there was a negative association between perceived stress and diabetes among those of high OS (OR: 0.60; 95% CI: 0.41-0.88) and no association within other occupational categories. The interaction between perceived stress and OS was significant (P<0.01). CONCLUSION: This study suggests that the association between perceived stress and diabetes onset is dependent on OS. Furthermore, this association does not appear to be explained by the classical risk factors for diabetes.

pH monitoring of gastro-oesophageal reflux before and after laparoscopic sleeve gastrectomy.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a common obesity-related co-morbidity that is assessed objectively by 24-h pH monitoring. Some concerns have been raised regarding the risk of de novo GORD or exacerbation of pre-existing GORD after laparoscopic sleeve gastrectomy. Here, 24-h pH monitoring was used to assess the influence of laparoscopic sleeve gastrectomy on postoperative GORD in obese patients with or without preoperative GORD. METHODS: From July 2012 to September 2014, all patients scheduled for laparoscopic sleeve gastrectomy were invited to participate in a prospective follow-up. Patients who underwent preoperative 24-h pH monitoring were asked to repeat the examination 6 months after operation. GORD was defined as an oesophageal pH < 4 for at least 4·2 per cent of the total time recorded. RESULTS: Of 89 patients, 76 had preoperative pH monitoring for GORD evaluation and 50 had postoperative reassessment. Patients without (group 1, 29 patients) or with (group 2, 21 patients) preoperative GORD were similar regarding age, sex ratio and body mass index. In group 1, the median (i.q.r.) total time at pH < 4 was significantly higher after surgery than before: 5·6 (2·5-9·5) versus 1·6 (0·7-2·9) per cent (P < 0·001). Twenty of the 29 patients experienced de novo GORD as determined by 24-h pH monitoring (P < 0·001). In group 2, total time at pH < 4 after surgery was no different from the preoperative value: 5·9 (3·9-10·7) versus 7·7 (5·2-10·3) per cent (P = 0·296). CONCLUSION: Laparoscopic sleeve gastrectomy was associated with de novo GORD in over two-thirds of patients, but did not seem to exacerbate existing GORD.

Individual 6-year systolic blood pressure change and impact on cardiovascular mortality in a French general population.

Impact of blood pressure (BP) visit-to-visit variability remains controversial for untreated hypertensives and for normotensive subjects. Association between 6-year systolic BP change and all-cause and cardiovascular (CVD) mortality was studied in general primary care population including untreated hypertensive and normotensive subjects. Normotensive individuals and untreated high BP patients (40,926 and 14,283, respectively) had two check-ups (interval: 5.8±2.2 years) at the IPC center (Paris). Follow-up was 6.1±3.2 years: 1131 people died, 114 from CVD causes. Systolic BP (SBP) change was assessed by tertiles of absolute differences between V1 and V2, and the relationship with mortality was analysed with multivariate Cox models (hazard ratio (HR), 95% confidence interval (CI)) including V1 or V2 parameters notably SBP. Adjusting for V1 variables, mortality was associated with SBP change, for the entire population (all-cause: HR=1.15 (95%: 1.01-1.30) and CVD: HR=1.95 (95%: 1.25-3.05)) and in hypertensive individuals: (HR=1.31 (95%: 1.08-1.59) and HR=2.51 (95%: 1.34-4.72), respectively). Adjustments for V2 variables gave similar results. For those who were normotensive at V1, the associations were not significant. In this primary care population, individual long-term visit-to-visit change of BP is an independent predictor of all-cause mortality in hypertensive individuals but not in those with normal BP.

Effects of blood pressure lowering on cardiovascular risk according to baseline body-mass index: a meta-analysis of randomised trials.

BACKGROUND: The cardiovascular benefits of blood pressure lowering in obese people compared with people of normal weight might depend on choice of drug. We compared the effects of blood pressure-lowering regimens on cardiovascular risk in groups of patients categorised by baseline body-mass index (BMI). METHODS: We used individual patient data from trials included in the Blood Pressure Lowering Treatment Trialists' Collaboration to compare the effects of different classes of blood pressure-lowering regimens for the primary outcome of total major cardiovascular events (stroke, coronary heart disease, heart failure, and cardiovascular death). We used meta-analyses and meta-regressions to assess interactions between treatment and BMI when fitted as either a categorical variable (<25 kg/m(2), 25 to <30 kg/m(2), and ≥30 kg/m(2)) or a continuous variable. FINDINGS: Analyses were based on 135,715 individuals from 22 trials who had 14,353 major cardiovascular events. None of the six primary comparisons showed evidence that protection varied by drug class across the three BMI groups (all p for trend >0·20). When analysed as a continuous variable, angiotensin-converting-enzyme inhibitors gave slightly greater protection for each 5 kg/m(2) higher BMI than did calcium antagonists (hazard ratio 0·93, 95% CI 0·89-0·98; p=0·004) or diuretics (0·93, 0·89-0·98; p=0·002). The meta-regressions showed no relation between BMI category and the risk reduction for a given fall in systolic blood pressure. By contrast with a previous report, we noted no relation between BMI and the efficacy of calcium antagonists compared with diuretics. INTERPRETATION: We found little evidence that selection of a particular class of blood pressure-lowering drug will lead to substantially different outcomes for individuals who are obese compared with those who are lean. FUNDING: None.