A Retrospective Study Examining Phentermine on Preconception Weight Loss and Pregnancy Outcomes

Objective: Obesity is a well-known risk factor for infertility. However, the use of weight loss medications prior to conception is underutilized. The objectives of our study are to describe weight loss, pregnancy rates, and live birth rates after short-term phentermine use in women with obesity and infertility.Methods: This was a retrospective analysis of 55 women (18 to 45 years old) who were overweight or obese, diagnosed with infertility, and prescribed phentermine for weight loss in an ambulatory endocrinology clinic at a single, tertiary level academic medical center. Main outcome measures were mean percent weight change at 3 months after starting phentermine, and pregnancy, and live birth rates from start of phentermine to June 30, 2017.Results: Median duration of phentermine use was 70 days (Q1, Q3 &lsqb;33, 129]). Mean ± SD percent weight change at 3 months after starting phentermine was -5.3 ± 4.1% (P<.001). The pregnancy rate was 60% and the live birth rate was 49%. There was no significant difference in pregnancy rates (52% versus 68%; P = .23) or live birth rates (44% versus 54%; P = .50) in women who lost ≥5% versus <5% of their baseline weight. The number of metabolic comorbidities was negatively associated with the pregnancy rate. Phentermine was generally well-tolerated with no serious adverse events.Conclusion: Phentermine can produce clinically significant weight loss in women with obesity during the preconception period. Higher pregnancy or live birth rates were not observed with a greater degree of weight loss with phentermine.     

Long-Term,Sustained, Lifestyle-Induced Weight Loss in Severe Obesity: the Get-Real Program

Objective: To study the long-term effectiveness of a patient-centered, multidisciplinary lifestyle intervention treatment in patients medically eligible for bariatric surgery.Methods: Using a case-control study design, we compared treatment results for 98 adults (mean body mass index [BMI], 44.2 kg/m²) with the outcomes of 148 controls (mean BMI, 43.0 kg/m²) receiving standard care. The approach included a phased triage for inclusion, followed by 12 lifestyle intervention group sessions alternating with individual visits for behavior, diet, and exercise instructions.Results: At 2 years, weight loss averaged 15.3 ± 1.4 kg (P<.0010) (12 ± 1% of initial body weight [IBW], P<.001; 21 ± 2% of excess body weight [EBW], P<.001) in an intention-to-treat (ITT) analysis; in completers, weight loss was 18.8 ± 1.5 kg (P<.001) (15 ± 1% IBW, P<.001; 26 ± 3% EBW, P<.001). A total of 42 patients lost ≥10% IBW. Controls remained weight stable (P =.35); 3% lost ≥10% IBW. Patients achieving weight loss that would be considered satisfactory for bariatric surgery included 20% who achieved ≥35% EBW loss, 29% who achieved a BMI <35 kg/m² (if starting BMI <50 kg/m²) or BMI <40 kg/m² (if starting BMI ≥50 kg/m²), and 37% who achieved EBW loss ≤50%. These values for completers were 31, 39, and 48%, respectively. In the 55 patients starting the program ≥4 years ago, weight loss maintenance of 12 ± 1% IBW (ITT, 16 ± 1% in completers) was observed.Conclusion: Substantial nonsurgical weight loss, maintained at 2 to 4 years, is achievable in severely obese patients using comprehensive lifestyle approaches; the efficacy/safety trade-off in obesity treatment is an important consideration in interpreting these results.Abbreviations: BMI = body mass index EBW = excess body weight HbA_1c = glycated hemoglobin IBW = initial body weight LOCFA = last observation carried forward analysis     

Predictors of Weight Loss in Adults with Topiramate‐Treated Epilepsy

Objective: We examined predictors of weight loss with topiramate, an anticonvulsant associated with weight loss in adults. Research Methods and Procedures: In this uncontrolled, prospective clinical trial, topiramate was added to existing anticonvulsants in adults (40 to 110 kg) with partial‐onset seizures. Primary measurements were change from baseline weight after 3 months and 1 year in patients completing 1 year of topiramate treatment (N = 38). Physiological and metabolic measures were analyzed for correlation with weight loss during topiramate treatment. Results: In patients who completed 1 year of topiramate treatment, baseline weight was reduced in 82% at 3 months and in 86% at 1 year. Mean body weight was reduced 3.0 kg (3.9% of baseline) at 3 months and 5.9 kg (7.3%) at 1 year. In obese patients [body mass index (BMI) ≥ 30 kg/m²], mean weight loss was 4.2 kg (4.3%) at 3 months and 10.9 kg (11.0%) at 1 year. Weight loss was primarily caused by reduction in body fat mass. For all patients, weight loss at 3 months correlated most strongly with reduced caloric intake (p = 0.02). At 1 year, caloric intake had returned to baseline levels; weight loss correlated most strongly with higher baseline BMI (p = 0.0007). Discussion: Our results suggest that weight loss occurs in most adults treated with topiramate and is sustained for at least 1 year. Reduced caloric intake may account, in part, for weight loss during early treatment. The pattern of weight loss differs according to baseline BMI, with obese patients experiencing greater weight loss during continued therapy.     

New Tools for Weight-Loss Therapy Enable a More Robust Medical Model for Obesity Treatment: Rationale for a Complications-Centric Approach

ObjectiveRecent advances in lifestyle intervention programs, pharmacotherapy, and bariatric surgery have enabled the development of medical models for the treatment of obesity. Regarding pharmacotherapy, in 2012 the U.S. Food and Drug Administration approved two new effective and safe weight-loss medications, phentermine/ topiramate extended release and lorcaserin, which has greatly augmented options for medically assisted weight loss.MethodsThe rationale for advantages of a complications-centric medical model over current body mass index (BMI)-centric indications for therapy is examined.ResultsCurrently, the baseline BMI level is the principle determinant of indications for obesity treatment using medication and surgery. However, the BMI-centric approach fails to target therapy to those obese patients who will benefit most from weight loss. In contrast, a complications-centric medical model is proposed that will earmark the modality and intensity of the therapeutic intervention based on the presence and severity of complications that can be ameliorated by weight loss.ConclusionThe complications-centric approach to “medicalizing” obesity care employs weight loss primarily as a tool to treat obesity-related complications and promotes the optimization of health outcomes, the benefit/risk ratio, and the cost-effectiveness of therapy. (Endocr Pract. 2013;19:864-874)     

One Month Weight Loss Predicts the Efficacy of Liraglutide in Obese Patients: Data from A Single Center

Objective: Liraglutide is a glucagon-like peptide 1 receptor agonist which acts through peripheral and central receptor pathways affecting food intake. Preliminary identification of responder patients represents a crucial point to reduce an inappropriate exposure to the drug and the health expenditure. The primary endpoint of our study was to identify predictors of liraglutide efficacy in the short term follow-up. The secondary endpoint was to evaluate the treatment efficacy stratified by the underlying psychiatric disorder.Methods: We evaluated a cohort of 100 patients (77 females, 23 males, mean body mass index 38.6 ± 3.2 kg/m²) who were evaluated at baseline, and after 1, 3, and 6 months of treatment. Liraglutide efficacy was defined by a weight loss ≥5% of initial weight. Sociodemographic/metabolic parameters, food intake, smoking habit, and physical activity were correlated with liraglutide efficacy.Results: There was a significant weight loss after 1 month of therapy, as well as after 3 and 6 months when compared to the baseline (P<.0001; 27%, 45%, and 57% of patients showed a weight loss ≥5%, respectively). No difference was found in weight loss between the 3 groups of patients (with binge eating, with/without psychiatric disorders). The weight loss at 1 month was the only predictor of a positive response to the treatment.Conclusion: Our results confirm the efficacy of liraglutide even at a lower dose than conventional. The early response to the drug seems to be a good predictor of long-term efficacy and it might be useful in clinical practice to identify patients in whom liraglutide may induce a significant weight loss.Abbreviations: BMI = body mass index; EMA = European Medicine Agency; FDA = Food and Drug Administration; GLP-1 RA = glucagon-like peptide 1 receptor agonist     

Anti-Obesity Pharmacotherapy and the Potential for Preventing Progression from Prediabetes to Type 2 Diabetes

Objective: Type 2 diabetes and its associated complications place heavy burdens on affected individuals, their caregivers, and society. The prevalence of type 2 diabetes is increasing worldwide. Attempts to combat this problem have been extended to the treatment of obesity and prevention of progression from prediabetes to type 2 diabetes. As such, weight loss is an important component of type 2 diabetes prevention. However, successful strategies for achieving sustained weight loss have remained elusive. Although lifestyle modification remains a cornerstone of this approach, it has become clear that changes to lifestyle alone will not suffice for many patients. A pragmatic approach includes consideration of pharmacotherapeutic options.Methods: This review discusses the different pharmacotherapeutic options for the treatment of obesity and prediabetes.Results: Approved anti-obesity therapies and antihyperglycemic agents associated with weight loss may prove effective earlier in the treatment paradigm, and other promising agents that are in clinical development for chronic weight management show promise for both weight reduction and a reduction in the risk of type 2 diabetes in high-risk individuals.Conclusion: Long-term evaluation of safety and efficacy is required for many of these agents before we can begin to optimize their use in clinical practice, but treatment choices for obese or prediabetic patients are increasing.Abbreviations: AACE = American Association of Clinical Endocrinologists ADA = American Diabetes Association AE = adverse event AMA = American Medical Association BMI = body mass index CI = confidence interval CR = controlled release DPP = Diabetes Prevention Program IFG = impaired fasting glucose IGT = impaired glucose tolerance FDA = Food and Drug Administration FPG = fasting plasma glucose GLP-1 = glucagon-like peptide-1 GLP-1 RA = glucagon-like peptide-1 receptor agonist HbA_1c= glycosylated hemoglobin ITT-LOCF = intention-totreat with last observation carried forward LS = least squares NB = naltrexone/bupropion OR = odds ratio PHEN = phentermine PYE = patient years of exposure PYY = peptide YY SGLT-2 = sodium glucose cotransporter 2 TPM = topiramate TZD = thiazolidinedione     

Metformin-Sustained Weight Loss and Reduced Android Fat Tissue At 12 Months In Empowir (Enhance The Metabolic Profile Of Women With Insulin Resistance): A Double Blind,Placebo-Controlled,Randomized Trial of Normoglycemic Women with Midlife Weight Gain

Objective: To assess 12-month body weight (BW) and body composition changes in normoglycemic women with midlife weight gain, after dietary and pharmacologic interventions targeting hyperinsulinemia.Methods: EMPOWIR (Enhance the Metabolic Profile of Women With Insulin Resistance; NCT00618072) was a double-blind, placebo-controlled, 12-month trial of women with >20-pound weight gain, normal glucose tolerance test, and increased area-under-the-curve insulin. Subjects (mean ± SD, 46.7 ± 6.5 years of age; body mass index, 30.8 ± 2.8 kg/m²; 50% white) attended 4 nutrition workshops to introduce a novel carbohydrate-modified diet (CMD) and were then randomized to one of three arms for 6 months (phase 1): CMD alone (D), or in combination with metformin (M), or metformin + rosiglitazone (MR), with rerandomization of the D group to one of the active treatment arms (phase 2, months 7 through 12). Repeated measure analysis of variance was used to assess BW at baseline, 6 months, and 12 months in 32 subjects with 12-month data; paired t tests compared baseline and 12-month dual-energy X-ray absorptiometry–derived body composition.Results: Mean (±SD) BW decreased significantly at 12 months in the M arm: 85.1 ± 8.5 kg to 79.8 ± 9.0 kg (P = .0003), with 54% of variance in weight over time explained by M treatment. Mean (±SD) percent android fat decreased significantly in the M and D arms: 53.5 ± 4.8% to 49.3 ± 7.6% (P = .010) and 52.9 ± 6.2% to 48.1 ± 8.7% (P = .021).Conclusion: In combination with a novel carbohydrate modified diet, metformin enhanced 12-month weight loss and improved body composition in ethnically diverse normoglycemic, hyperinsulinemic women with midlife weight gain. These findings suggest that EMPOWIR's easily implemented dietary interventions, alone and in combination with pharmacotherapies that target hyperinsulinemia, merit additional investigation in larger, long-term studies.Abbreviations:ANOVA = analysis of varianceBC = body compositionBW = body weightCMD = carbohydrate-modified dietD = diet alone groupDXA = dual-energy X-ray absorptiometryEMPOWIR = Enhance the Metabolic Profile of Women With Insulin ResistanceM = metformin groupMR = metformin + rosiglitazone group     

Effects of Liraglutide 3.0 Mg on Weight and Risk Factors in Hispanic Versus Non-Hipanic Populations: Subgroup Analysis from Scale Randomized Trials

Objective: Scarce data exist on pharmacotherapy for obesity in Hispanic individuals. This post hoc analysis of pooled data from 4 phase 3a trials compared the efficacy and safety of liraglutide 3.0 mg versus placebo, as adjunct to a reduced-calorie diet and physical activity, in Hispanic versus non-Hispanic subgroups.Methods: We conducted the double-blind randomized, placebo-controlled trials in adults with a minimum body mass index (BMI) of 27 kg/m² with at least 1 comorbidity, or a minimum BMI of 30 kg/m², at clinical research sites worldwide. In this analysis, we investigated possible differences in treatment effects between 534 Hispanics (10.4% of the population) and 4,597 non-Hispanics (89.6%) through statistical tests of interaction between subgroups and treatment. Variables examined included mean and categorical weight change, cardiovascular risk markers, and safety data.Results: Both subgroups achieved clinically significant mean weight loss at end-of-treatment with liraglutide 3.0 mg versus placebo: Hispanics 7.0% versus 1.5%, treatment difference -5.1% (95% CI, -6.2 to -4.0); non-Hispanics 7.5% versus 2.3%, -5.2% (95% CI, -5.5 to -4.8). More individuals in both subgroups lost ≥5%, >10%, and >15% of their baseline weight with liraglutide 3.0 mg than with placebo. Efficacy endpoints generally did not vary with ethnicity (P>.05). Adverse events were comparable between ethnic subgroups, with more gastrointestinal disorders reported with liraglutide 3.0 mg than placebo.Conclusion: Efficacy and safety were largely similar between Hispanic and non-Hispanic subgroups. Results support that liraglutide 3.0 mg, used with a reduced-calorie diet and physical activity, can facilitate weight loss in Hispanic individuals.Abbreviations:A1c = glycated hemoglobinBMI = body mass indexCI = confidence intervalFPG = fasting plasma glucoseGLP-1 = glucagon-like peptide-1hsCRP = high-sensitivity C-reactive proteinSCALE = Satiety and Clinical Adiposity – Liraglutide Evidence in individuals with and without diabetesT2DM = type 2 diabetes mellitus     

SGLT-2 Inhibitor Therapy Added to GLP-1 Agonist Therapy in the Management of T2DM

Objective: To assess the real-world efficacy and safety of canagliflozin therapy added to type 2 diabetes mellitus (T2DM) patients who have received a minimum 1 year of glucagon-like peptide-1 (GLP-1) agonist therapy.Methods: This pre-post observational study assessed the efficacy and safety of canagliflozin in a group of T2DM patients from a community endocrinology practice who received GLP-1 agonist therapy for a minimum of 12 months. The primary study outcome was change in mean glycated hemoglobin (HbA1c) level from baseline. Secondary endpoints included changes in average weight, and comparison of the percentage of patients obtaining an HbA1c <7%.Results: A total of 75 patients met all the study criteria. Baseline patient characteristics were as follows: average age, 58 ± 9 years; mean duration of T2DM, 14 ± 6 years; 56% male; 92% Caucasian; baseline body mass index (BMI), 39.4 ± 9.4 kg/m²; and mean baseline HbA1c, 7.94 ± 0.69%. HbA1c and weight were significantly reduced by 0.39% and 4.6 kg, respectively. Adverse effects were reported by 13 (17.3%) patients, including 4 (5.3%) who discontinued canagliflozin because of adverse reactions.Conclusion: Canagliflozin was generally well tolerated and significantly further reduced mean HbA1c levels and body weight in patients with T2DM when added to GLP-1 regimen.Abbreviations:BP = blood pressureBUN = blood urea nitrogenCANTATA = Canagliflozin Treatment and Trial AnalysisDBP = diastolic blood pressureDKA = diabetic ketoacidosisDPP-4 = dipeptidyl peptidase-4EMR = electronic medical recordFDA = Food and Drug AdministrationGFR = glomerular filtration rateGLP-1 = glucagon-like peptide-1HbA1c = glycated hemoglobinHDL-C = high-density lipoprotein cholesterolLDL-C = low-density lipoprotein cholesterolSCr = serum creatinineSGLT-2 = sodium glucose cotransporter 2T2DM = type 2 diabetes mellitusTZD = thiazolidinedioneUTI = urinary tract infection     

Patient Perspectives on Obesity Management: Need for Greater Discussion of BMI and Weight-Loss Options Beyond Diet and Exercise,Especially in Patients With Diabetes

Objective: To identify perceptions of obesity management in patients with and without diabetes.Methods: A 48-question survey was administered in 2018 to our Endocrinology Clinic's adult patients with a body mass index (BMI) ≥30 kg/m². Chi-squared or Fisher's exact tests were used to compare variables between groups.Results: Of 146 respondents, 105 had diabetes and 41 did not. Most respondents were female (61.4%), African American (66.4%), and with an income <$50,000 (58.6%). Those with diabetes had significantly greater comorbidities of hypertension, high cholesterol, and arthritis. Over 90% in both groups agreed that obesity is related to hypertension, diabetes, heart disease, and early death. Only 48% were aware of their BMI, and only 30.5% with diabetes and 41.5% without diabetes perceived themselves to be obese. Over 60% in each group reported discussion of diet and exercise with their providers, whereas few in both groups reported referral to a formal weight-loss program (18.9%) or to a specialty that manages obesity (4.2%), or discussion of anti-obesity medications (11.2%) or bariatric surgery (8.4%). Reported concerns with anti-obesity medications and bariatric surgery included lack of knowledge and side effects or complications.Conclusion: These findings revealed excellent patient awareness of obesity as a health problem but misperception of obese status and unawareness of BMI. Presence of diabetes and other comorbidities did not result in greater discussion of weight-loss methods beyond diet and exercise. Increased patient education and discussion of specific weight-loss services, anti-obesity medications, and bariatric surgery are needed.Abbreviations: BMI = body mass index; DM = diabetes mellitus; HbA1c = hemoglobin A1c; HCP = healthcare provider     

Effects of Sibutramine Plus Orlistat in Obese Women Following 1 Year of Treatment by Sibutramine Alone: A Placebo‐Controlled Trial

Objective: This study assessed whether adding orlistat to sibutramine would induce further weight loss in patients who previously had lost weight while taking sibutramine alone. Research Methods and Procedures: Patients were 34 women with a mean age of 44.1 ± 10.4 years, weight of 89.4 ± 13.8 kg, and body mass index (BMI) of 33.9 ± 4.9 kg/m² who had lost an average of 11.6 ± 9.2% of initial weight during the prior 1 year of treatment by sibutramine combined with lifestyle modification. Patients were randomly assigned, in double‐blind fashion, to sibutramine plus orlistat or sibutramine plus placebo. In addition to medication, participants were provided five brief lifestyle modification visits during the 16‐week continuation trial. Results: Mean body weight did not change significantly in either treatment condition during the 16 weeks. The addition of orlistat to sibutramine did not induce further weight loss as compared with treatment by sibutramine alone (mean changes = +0.1 ± 4.1 kg vs. +0.5 ± 2.1 kg, respectively). Discussion: These results must be interpreted with caution because of the study's small sample size. The findings, however, suggest that the combination of sibutramine and orlistat is unlikely to have additive effects that will yield mean losses ≥15% of initial weight, as desired by many obese individuals.     

Increased Bone Turnover in Type 2 Diabetes Patients Randomized to Bariatric Surgery Versus Medical Therapy at 5 Years

Objective: The aim of our study was to determine the 5-year outcomes of bariatric surgery versus intensive medical therapy on bone turnover in patients with type 2 diabetes mellitus (T2DM) from the STAMPEDE trial.Methods: This was an ancillary investigation of a 5-year randomized control trial at a single tertiary care center involving 95 patients aged 48.5 ± 8 years with obesity (body mass index &lsqb;BMI], 36.5 ± 3.6 kg/m²) and uncontrolled T2DM (glycated hemoglobin 9.3 ± 1.6% &lsqb;78 mmol/mol]). Patients were randomized to intensive medical therapy (IMT; n = 25), Roux-en-Y gastric bypass (RYGB; n = 37), or sleeve gastrectomy (SG; n = 33) for diabetes treatment. Bone formation marker osteocalcin (OC), bone resorption marker serum C-telopeptide of type 1 collagen (CTX), and intact parathyroid hormone (PTH) were assessed at baseline and 5 years postintervention. Analysis with key clinical parameters and outcomes (i.e., age, menopausal status, gender, weight loss) was performed.Results: Percent change in CTX at 5 years increased in both surgical groups, by 137 ± 108% in RYGB (P<.001) and 61.1 ± 90% in SG (P<.001) compared to 29.8 ± 93% in IMT (P = .12). OC also increased from baseline in the surgical cohorts, by 138 ± 19% in RYGB (P<.001) and 71 ± 69% in SG (P<.001) compared to 43.8 ± 121.1% in IMT (P = .83). Increases in both CTX and OC correlated linearly with increases in PTH levels in RYGB patients (P<.001). Increase in CTX correlated with decreased BMI in SG patients (P = .039).Conclusion: In patients with T2DM, bone turnover remains chronically elevated at 5 years following RYGB, and to a lesser extent in SG patients.Abbreviations: BMI = body mass index; BTM = bone turnover marker; CTX = C-telopeptide of type 1 collagen; HbA1c = glycated hemoglobin; IMT = intensive medical therapy; OC = osteocalcin; PPI = proton-pump inhibitor; PTH = parathyroid hormone; RYGB = Roux-en-Y gastric bypass; SG = sleeve gastrectomy; T2DM = type 2 diabetes mellitus; TZD = thiazolidinedione     

Long‐term Successful Weight Loss Improves Vascular Endothelial Function in Severely Obese Individuals

Obesity is associated with increased cardiovascular risk. Although short‐term weight loss improves vascular endothelial function, longer term outcomes have not been widely investigated. We examined brachial artery endothelium‐dependent vasodilation and metabolic parameters in 29 severely obese subjects who lost ≥10% body weight (age 45 ± 13 years; BMI 48 ± 9 kg/m²) at baseline and after 12 months of dietary and/or surgical intervention. We compared these parameters to 14 obese individuals (age 49 ± 11 years; BMI 39 ± 7 kg/m²) who failed to lose weight. For the entire group, mean brachial artery flow‐mediated dilation (FMD) was impaired at 6.7 ± 4.1%. Following sustained weight loss, FMD increased significantly from 6.8 ± 4.2 to 10.0 ± 4.7%, but remained blunted in patients without weight decline from 6.5 ± 4.0 to 5.7 ± 4.1%, P = 0.013 by ANOVA. Endothelium‐independent, nitroglycerin‐mediated dilation (NMD) was unaltered. BMI fell by 13 ± 7 kg/m² following successful weight intervention and was associated with reduced total and low‐density lipoprotein cholesterol, glucose, hemoglobin A_1c, and high‐sensitivity C‐reactive protein (CRP). Vascular improvement correlated most strongly with glucose levels (r = ?0.51, P = 0.002) and was independent of weight change. In this cohort of severely obese subjects, sustained weight loss at 1 year improved vascular function and metabolic parameters. The findings suggest that reversal of endothelial dysfunction and restoration of arterial homeostasis could potentially reduce cardiovascular risk. The results also demonstrate that metabolic changes in association with weight loss are stronger determinants of vascular phenotype than degree of weight reduction.     

Greater Combined Reductions in Hba1C ≥1.0% and Weight ≥5.0% with Semaglutide Versus Comparators in type 2 Diabetes

Objective: Semaglutide is a glucagon-like peptide 1 (GLP-1) analog for the once-weekly treatment of type 2 diabetes (T2D). In the global SUSTAIN clinical trial program, semaglutide demonstrated superior glycated hemoglobin (HbA_1c) and body weight reductions versus comparators. This post hoc analysis compared the proportion of patients achieving combined reductions in glycemia and body weight versus comparators.Methods: A total of 5,119 subjects with T2D in the phase 3 SUSTAIN 1 through 5 and 7 trials, from 33 countries, were included in this post hoc analysis. Subjects received subcutaneous semaglutide 0.5 or 1.0 mg, placebo or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg, insulin glargine, dulaglutide 0.75 or 1.5 mg). The main endpoint was a composite of ≥1.0% HbA_1c reduction and ≥5.0% weight loss at end of treatment.Results: Significantly greater proportions of subjects achieved the composite endpoint with semaglutide 0.5 (25 to 38%) and 1.0 mg (38 to 59%) versus comparators (2 to 23%). More subjects treated with semaglutide versus comparators achieved ≥1.0% HbA_1c reductions (58 to 77% and 75 to 83% for semaglutide 0.5 and 1.0 mg versus 12 to 68%) and ≥5.0% weight loss (37 to 46%, 45 to 66% versus 4 to 30%). Proportions of subjects achieving targets were significantly higher with semaglutide 1.0 versus 0.5 mg in four of five trials. Semaglutide was well tolerated, with a safety profile similar to other GLP-1 receptor agonists.Conclusion: Significantly more subjects achieved both ≥1.0% HbA_1c reduction and ≥5.0% weight loss with once-weekly subcutaneous semaglutide treatment versus comparators in the SUSTAIN trials. A dose-dependent effect was observed with semaglutide.Abbreviations: AE = adverse event; CV = cardiovascular; ER = extended release; GLP-1 = glucagon-like peptide 1; GLP-1 RA = glucagon-like peptide 1 receptor agonist; HbA_1c = glycated hemoglobin; OAD = oral antidiabetic drug; sc = subcutaneous; T2D = type 2 diabetes     

Visceral and Subcutaneous Fat Increased after Treatment of Graves Disease

Objective: Patients with Graves disease (GD) tend to gain weight after treatment, but it remains unknown if weight gain is associated with an increase in the visceral and/or subcutaneous fat areas (VFA, SFA).Methods: We enrolled 25 newly diagnosed GD patients (22 females, median age 33.0 years) and studied their clinical parameters, and VFA and SFA measured by a dual bioelectric impedance analysis. We divided them into 2 groups based on the rates of change in the VFA and SFA, and we compared clinical parameters at the baseline between the groups to evaluate factors that influence increases in the VFA and/or SFA with treatment.Results: The patients' body weight (BW), VFA, and SFA were significantly increased after a 6-month treatment (BW: from 54.3 ± 10.3 kg to 58.0 ± 11.2 kg; P<.001; VFA: from 47.1 ± 21.3 cm² to 54.7 ± 23.4 cm²; P = .004; SFA: from 159.8 ± 85.9 cm² to 182.2 ± 82.9 cm²; P = .008). The percent changes of BW correlated with the SFA (ρ = .591, P = .002), but not with the VFA. The patients with larger VFA increases had significantly less VFA at the baseline compared to those with smaller increases, expressed as median and interquartile range (33.9 cm² [22.7 to 47.5 cm²] versus 54.5 cm² [45.2 to 64.0], respectively; P = .011). A larger increase in the SFA was negatively associated with serum alkaline phosphatase. An increase in the SFA was associated with free triiodothyronine (T3) in a multivariate logistic analysis (odds ratio: 0.80 [0.59 to 0.97]; P = .013).Conclusion: The patients' BW, VFA, and SFA were increased after GD treatment. The increase in SFA seemed to contribute to weight gain and was associated with a low baseline level of free T3.Abbreviations: ALP = alkaline phosphatase; BMI = body mass index; BW = body weight; GD = Graves disease; SFA = subcutaneous fat area; T3 = triiodothyronine; T4 = thyroxine; TG = triglycerides; VFA = visceral fat areas     

Impact of Weight Loss and Regain on Quality of Life: Mirror Image or Differential Effect?

Objective: To compare the impact of weight regain and weight loss on health‐related quality of life. Research Methods and Procedures: Subjects were 122 (106 women, 16 men) overweight and obese participants in a weight reduction program (phentermine‐fenfluramine and dietary counseling) who had initially lost at least 5% of their total body weight and then regained at least 5% of their weight during the follow‐up period. Follow‐up periods ranged from 10 to 41 months (mean, 28 months). Participants completed the Impact of Weight on Quality of Life‐Lite, an obesity‐specific health‐related quality of life (HRQOL) measure, at 3‐month intervals. Results: Mean BMI at baseline was 40.9 ± 6.6 kg/m² (range, 29.2 to 63.7 kg/m²). Average weight loss from entry was 18.8 ± 6.7% (range, 6.0% to 43.7%), and average regain was 10.1 ±4.4% of baseline weight (range, 5.0% to 30.6%). The effects of weight regain on HRQOL mirrored the effects of weight loss—rates of HRQOL change were similar in magnitude but different in direction for comparable weight loss and regain. Those with more severe initial impairments in HRQOL experienced greater improvements in HRQOL during weight loss as well as greater deterioration during weight regain than those with less severe impairments. Discussion: Weight loss and regain produced mirror image changes in HRQOL. The initial severity of HRQOL impairment had a greater impact on the magnitude of HRQOL change than the direction of weight change. Findings underscore the importance of maintaining weight loss for the purposes of retaining obesity‐specific HRQOL benefits.     

Failure to meet weight loss expectations does not impact maintenance in successful weight losers

Objective: The objective was to examine whether having a weight loss experience that lives up to one's expectations is related to maintenance in a group of successful weight losers participating in the STOP Regain trial. Research Methods and Procedures: Participants (N = 314, 81% women, mean age, 51.3 ± 10.1 years; BMI = 28.6 ± 4.8 kg/m²) who lost ≥10% of their body weight within the past 2 years were randomly assigned to a maintenance program delivered either face‐to‐face or via the Internet or to a control group and assessed at 0, 6, 12, and 18 months. Results: At study entry, participants had lost 19% of their body weight, yet 86% of participants were currently trying to lose more weight. Further losses of 13% of body weight were needed to reach self‐selected ideal weights, with heavier participants wanting to lose more (p < 0.001). The weight loss‐related benefits participants achieved did not live up to their expectations (p ≤ 0.01). However, neither satisfaction with current weight, nor amount of further weight loss desired, nor discrepancies between actual and expected benefits predicted regain after adjusting for treatment group, gender, baseline weight, and percent weight loss before entry. Discussion: Even among very successful weight losers, expectations were not met and substantial further weight losses were desired; however, these factors were not related to subsequent weight maintenance outcomes.     

Prevalence of Obstructive Sleep Apnea Determined by the Watchpat in Nonobese Japanese Patients with Poor Glucose Control And Type 2 Diabetes

Objective: Diagnosing obstructive sleep apnea (OSA) usually involves high cost, patient inconvenience, and the need for examination at a specialized center. This study employed a portable, wearable, diagnostic device (WatchPAT) to investigate the prevalence of OSA in nonobese Japanese patients with type 2 diabetes.Methods: Patients with type 2 diabetes were tested for OSA over one night using the WatchPAT. Logistic regression analysis was used to estimate the odds ratios (ORs) of risk factors for OSA in nonobese subjects.Results: A total of 200 eligible patients with type 2 diabetes were studied (64.5% men; aged 60.1 ± 13.6 years; body mass index &lsqb;BMI], 26.3 ± 5.2 kg/m²). When OSA was defined as apnea-hypopnea index ≥5/hour, its prevalence was 80.5%. The prevalence of OSA in subjects with a BMI <20 kg/m², ≥20 and <25 kg/m², ≥25 and <30 kg/m², and ≥30 kg/m² was 38.9%, 73.5%, 86.5%, and 97.5%, respectively. The severity of OSA increased in proportion to BMI, especially when the BMI was >25 kg/m². The prevalence of OSA was also high (66.3%) in normal-weight subjects (BMI <25 kg/m²). Furthermore, the serum triglyceride level (OR, 1.01; 95% confidence interval, 1.00 to 1.02; P = .042) was significantly related to OSA.Conclusion: A high prevalence of OSA was observed in this nonobese population of Japanese patients with type 2 diabetes. The triglyceride level was associated with OSA among nonobese patients.Abbreviations: AHI = apnea-hypopnea Index; BMI = body mass index; CI = confidence interval; ESS = Epworth Sleepiness Scale; HbA1c = glycated hemoglobin; OR = odds ratio; OSA = obstructive sleep apnea; PAT = peripheral arterial tone; T2D = type 2 diabetes; TG = triglyceride     

Provider Practice Habits And Barriers To Care In Obesity Management In A Large Multicenter Health System

Objective: To identify provider recommendations and barriers in obesity management in a multicenter academic health system with extensive weight-loss management resources.Methods: A 26-question online survey was sent to attending physicians, trainees, and advanced practice providers in primary care specialties (internal medicine, family medicine, women's health) and endocrinology.Results: The survey response rate was 26% (111/430). Of respondents, 50% were internal medicine, 24% family medicine, 16% women's health, and 9% endocrinology. The majority were attending physicians (54%) and residents (40%). About 50% of respondents advised weight loss for a body mass index (BMI) >30 kg/m² in >50% of clinic visits. Limited time (82%) was the most common reason for not discussing weight loss, followed by the perception that discussion would not change patient behavior, insufficient knowledge, and discomfort broaching the subject. Common barriers to prescribing anti-obesity medications included limited experience (57%) and concern for adverse reactions (26%). Only 44% offered bariatric surgery to >50% of their patients who met criteria. Primary reasons for not referring included concerns of high surgical risk from comorbidities (57%) and potential adverse events (32%). Endocrinology had the highest referral to surgery. Attending physicians and fellows were more likely than residents to advise weight loss at lower BMI, offer medications, and refer to bariatric surgery.Conclusion: Our study reveals reluctance and lack of primary care confidence in managing obesity with pharmacotherapy and bariatric surgery, especially in the earlier stages of obesity. Barriers to care include lack of clinic time, limited experience, and concerns about treatment risks.Abbreviations: BMI = body mass index; HbA1c = hemoglobin A1c; IRB = Institutional Review Board     

Treatment of Hypothalamic Obesity with Caffeine and Ephedrine

ObjectiveTo investigate the hypothesis that the peripheral actions of caffeine and ephedrine to increase sympathetic tone and metabolic rate and to preserve lean tissue will cause weight loss in patients with hypothalamic obesity.MethodsWe present 3 case studies of consecutive patients who presented with hypothalamic obesity and were treated with caffeine (200 mg) and ephedrine hydrochloride (25 mg) 3 times a day.ResultsAll patients were gaining weight at the time of initial assessment. The first patient lost 8% to 9% of her body weight and maintained that loss for the subsequent 2 years. The second patient lost 18.8% of her body weight and was maintaining a 9.5% weight loss after 6 years. The third patient lost 14% of her body weight during a 6- month period and gradually returned to her baseline weight during a period of 5 years, after which she was referred for bariatric surgical treatment.ConclusionThese 3 patients with hypothalamic obesity, who had been steadily gaining weight, lost a mean of 13.9% of their body weight, and 2 of them maintained weight loss for a period of years. Thus, caffeine and ephedrine appeared to halt weight gain and maintain a clinically significant weight loss in 2 of our 3 patients. A randomized clinical trial to confirm these findings would be appropriate but difficult because of the rarity of this disorder. (Endocr Pract. 2008;14:697-703)