Exenatide, Dapagliflozin, or Phentermine/Topiramate Differentially Affect Metabolic Profiles in Polycystic Ovary Syndrome.

CONTEXT: Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors reduce weight and improve insulin sensitivity via different mechanisms. OBJECTIVE: The efficacy of once-weekly exenatide (EQW) and dapagliflozin (DAPA) alone and coadministered (EQW/DAPA), DAPA/extended-release (ER) metformin (DAPA/MET), and phentermine topiramate extended release (PHEN/TPM) on metabolic parameters, body composition, and sex hormones were examined in obese women with PCOS. METHODS: Nondiabetic women (n = 119; aged 18-45 years) with a body mass index (BMI) greater than 30 and less than 45 and polycystic ovary syndrome (National Institutes of Health criteria) were randomly assigned in a single-blinded fashion to EQW (2 mg weekly); DAPA (10 mg daily), EQW/DAPA (2 mg weekly/10 mg daily), DAPA (10 mg)/MET (2000 mg XR daily), or PHEN (7.5 mg)/TPM (46 mg ER daily) treatment for 24 weeks. Study visits at baseline and 24 weeks included weight, blood pressure (BP), waist (WC) measures, and body composition evaluated by dual-energy x-ray absorptiometry (DXA). Oral glucose tolerance tests were conducted to assess glycemia and mean blood glucose (MBG), and compute insulin sensitivity (SI) and secretion (IS) measures. Sex steroids, free androgen index (FAI), and lipid profiles were measured in the fasting sample. RESULTS: EQW/DAPA and PHEN/TPM resulted in the most loss of weight and total body fat by DXA, and WC. Despite equivalent reductions in BMI and WC with PHEN/TPM, only EQW/DAPA and EQW resulted in significant improvements in MBG, SI, and IS. Reductions in fasting glucose, testosterone, FAI, and BP were seen with all drugs. CONCLUSION: Dual therapy with EQW/DAPA was superior to either alone, DAPA/MET and PHEN/TPM in terms of clinical and metabolic benefits in this patient population.

Efficacy and Safety of Phentermine/Topiramate in Adults with Overweight or Obesity: A Systematic Review and Meta-Analysis.

OBJECTIVE: The study objective was to examine the association between phentermine/topiramate therapy and weight loss and adverse events in adults with overweight or obesity by meta-analysis and systematic review. METHODS: Medical Subject Headings and free-text terms were selected to search for eligible trials in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase up to April 18, 2020. The quality of randomized controlled trials was evaluated by the Cochrane risk-of-bias tool. Meta-analysis was performed using random-effect models. RESULTS: Phentermine/topiramate therapy resulted in an average weight loss of 7.73 kg (95% CI: 6.60-8.85) in general compared with placebo. The weight loss was related to the dose of phentermine/topiramate. Compared with placebo, the average weight loss was 3.55 kg (95% CI: 2.22-4.88) for 3.75/23 mg, 7.27 kg (95% CI: 6.40-8.13) for 7.5/46 mg, and 8.25 kg (95% CI: 6.92-9.79) for 15/92 mg. For phentermine/topiramate participants in different weight-loss subgroups, the weight loss of participants with ≥5%, ≥10%, and ≥15% baseline weight loss was 3.18 (95% CI: 2.75-3.67), 5.32 (95% CI: 4.53-6.25), and 5.65 (95% CI: 3.55-9.01), respectively. Compared with placebo, the adverse events associated with the treatment mainly included dysgeusia (odds ratio [OR] = 8.86, 95% CI: 5.65-13.89), paresthesia (OR = 8.51, 95% CI: 6.20-11.67), dry mouth (OR = 6.71, 95% CI: 5.03-8.94), disturbance in attention (OR = 4.48, 95% CI: 2.39-8.41), irritability (OR = 4.10, 95% CI: 2.29-7.33), hypoesthesia (OR = 3.81, 95% CI: 1.32-11.00), constipation (OR = 2.43, 95% CI: 2.02-2.93), and dizziness (OR = 2.26, 95% CI: 1.72-2.98). Phentermine/topiramate also reduced waist circumference, blood pressure, blood sugar levels, and lipid levels. CONCLUSIONS: Phentermine/topiramate has considerable benefit in reducing body weight, and the efficacy was closely related to the dosage. However, it increased the risk of nervous system-related adverse events.

Pharmacotherapy for Weight Loss in Cirrhosis and Liver Transplantation: Translating the Data and Underused Potential.

BACKGROUND AND AIMS: Thirty percent of patients with cirrhosis are obese and the prevalence of obesity increases after transplant to >40% post-transplant. There are currently four weight loss medications approved by the FDA for treatment of obesity (orlistat, phentermine-topiramate, naltrexone-bupropion, and liraglutide). The aim of this review was to investigate the data on the use of these weight loss medications and alternative medicines in patients with cirrhosis and in liver transplant recipients (LTRs). APPROACH AND RESULTS: While there is paucity of data for these medications in patients with cirrhosis and LTRs, Liraglutide appears to be generally safe in view of its pharmacokinetic properties. Phentermine-topiramate seems to have the highest weight loss potential but special consideration should be given to neuropsychiatric disorders, cardiovascular comorbidities, and drug interactions. There are emerging data on use of alternative medicines for weight loss but more data are needed. CONCLUSIONS: The use of weight loss medications is feasible in this patient population but the decision of which medication to prescribe should be individualized based on the degree of renal and hepatic impairment, other co-morbidities, and concomitant medications.

Effect of JumpstartMD, a Commercial Low-Calorie Low-Carbohydrate Physician-Supervised Weight Loss Program, on 22,407 Adults.

Background: Commercial weight loss programs provide valuable consumer options for those desiring support. Several commercial programs are reported to produce ≥3-fold greater weight loss than self-directed dieting. The effectiveness of JumpstartMD, a commercial pay-as-you-go program that emphasizes a low-to-very-low-carbohydrate real-food diet and optional pharmacologic treatment without prepackaged meals or meal replacement, has not previously been described. Methods: Completer and last observation carried forward (LOCF) of clinic-measured weight loss (kg) in 18,769 female and 3638 male JumpstartMD participants. Results: Completers lost (mean ± SE) 8.7 ± 0.04 kg, 9.5 ± 0.04% with 44.5 ± 0.5% achieving ≥10% weight loss at 3 months (mo, N = 14,999 completers); 11.8 ± 0.1 kg, 12.6 ± 0.1% with 66.4 ± 0.6% achieving ≥10% weight loss at 6 mo (N = 11,805); and 11.5 ± 0.2 kg, 12.0 ± 0.2% with 57.6 ± 0.9% achieving ≥10% weight loss at 12 mo (N = 8514). LOCF estimates were -6.5 ± 0.03 kg, -7.2 ± 0.03% with 27.1 ± 0.3% achieving ≥10% weight loss at 3 mo; -7.7 ± 0.04 kg, -8.5 ± 0.04% with 36.3 ± 0.3% achieving ≥10% weight loss at 6 mo; and -7.7 ± 0.1 kg, -8.4 ± 0.1% with 34.6 ± 0.3% achieving ≥10% weight loss after 12 mo. Frequent health coach meetings was a major determinant of weight loss, with women and men attending ≥75% of their weekly appointments losing 8.8 ± 0.04 and 11.9 ± 0.1 kg, respectively, after 3 mo, 13.1 ± 0.1 and 16.5 ± 0.3 kg after 6 mo, and 16.5 ± 0.3 and 19.4 ± 0.8 kg after 12 mo. Phentermine and phendimetrazine had a minor effect in women only at 1 (6.1% greater weight loss than untreated), 2 (4.1%), and 3 mo (1.2%), but treated patients showed longer enrollment than nontreated during the first 3 (females: +0.4 ± 0.01; males: +0.3 ± 0.04 mo), 6 (females: +1.1 ± 0.04; males: +1.0 ± 0.1 mo), and 12 mo (females: +2.7 ± 0.1; males: +2.4 ± 0.2 mo). JumpstartMD produced generally greater weight loss than published reports for other real-food and prepackaged-meal commercial programs and somewhat greater or comparable losses to meal replacement diets. Conclusion: A one-on-one medically supervised program that emphasized real low-carbohydrate foods produced effective weight loss, particularly in those attending ≥75% of their weekly appointments.

Phentermine and Coronary Vasospasm-Induced Myocardial Infarction.

Women presenting to the cardiac catheterization laboratory with normal coronary arteries without significant atherosclerotic disease is a common presentation. In such patients, it is important to maintain a wide differential and consider alternate diagnoses. We present two cases of women presenting with chest pain found to have severe coronary vasospasm in the setting of recent initiation of phentermine. Phentermine may have vasospastic proprieties which are important to consider when prescribing to patients.

A randomized, double-blind, placebo-controlled, crossover study to evaluate the human abuse liability of solriamfetol, a selective dopamine and norepinephrine reuptake inhibitor.

BACKGROUND: This study evaluated the human abuse potential of solriamfetol (formerly JZP-110), a selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects. METHODS: Adults with a recent history of recreational polydrug use, including stimulants, and who met criteria in a Qualification Phase were randomized to one of six sequences in a Test Phase. Each Test Phase sequence included a single administration of placebo, solriamfetol (300, 600, and 1200 mg), and phentermine (45 and 90 mg), with a two-day washout between periods. The primary endpoint was peak rating ( Emax) of Liking at the Moment across the first 12 h on a liking/disliking visual analog scale; key secondary endpoints were Next Day Overall Drug Liking, how much the participant would like to Take the Drug Again, and positive and negative subjective effects. Safety was also assessed throughout the study. RESULTS: Of 43 participants (74.4% male; mean age 29.3 years), 37 completed the study. Peak Emax Liking at the Moment for all solriamfetol doses was significantly greater than placebo and significantly less than phentermine 90 mg ( p < 0.05). Overall Next Day Drug Liking was greater than placebo for solriamfetol 300 mg and phentermine 45 and 90 mg ( p < 0.05). Willingness to Take the Drug Again was significantly greater than placebo and significantly less than both doses of phentermine for all doses of solriamfetol ( p < 0.05). Ratings of negative subjective effects (bad effects, disliking, anxiety, agitation) were higher with solriamfetol 600 and 1200 mg relative to phentermine. The most common treatment-emergent adverse events with solriamfetol were hypervigilance, elevated mood, dry mouth, hyperhidrosis, and insomnia. CONCLUSION: Solriamfetol appears to have abuse potential similar to or lower than phentermine.

Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa.

INTRODUCTION: Bulimia nervosa (BN) and binge eating disorder (BED) are associated with severe psychological and medical consequences. Current therapies are limited, leaving up to 50% of patients symptomatic despite treatment, underscoring the need for additional treatment options. Qsymia, an FDA-approved medication for obesity, combines phentermine and topiramate ER. Topiramate has demonstrated efficacy for both BED and BN, but limited tolerability. Phentermine is FDA-approved for weight loss. A rationale for combined phentermine/topiramate for BED and BN is improved tolerability and efficacy. While a prior case series exploring Qsymia for BED showed promise, randomized studies are needed to evaluate Qsymia's safety and efficacy when re-purposed in eating disorders. We present a study protocol for a Phase I/IIa single-center, prospective, double-blinded, randomized, crossover trial examining safety and preliminary efficacy of Qsymia for BED and BN. METHODS: Adults with BED (n=15) or BN (n=15) are randomized 1:1 to receive 12weeks Qsymia (phentermine/topiramate ER, 3.75mg/23mg-15mg/92mg) or placebo, followed by 2-weeks washout and 12-weeks crossover, where those on Qsymia receive placebo and vice versa. Subsequently participants receive 8weeks follow-up off study medications. The primary outcome is the number of binge days/week measured by EDE. Secondary outcomes include average number of binge episodes, percentage abstinence from binge eating, and changes in weight/vitals, eating psychopathology, and mood. DISCUSSION: To our knowledge this is the first randomized, double-blind protocol investigating the safety and efficacy of phentermine/topiramate in BED and BN. We highlight the background and rationale for this study, including the advantages of a crossover design. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824.

Observational Comparative Effectiveness of Pharmaceutical Treatments for Obesity within the Veterans Health Administration.

STUDY OBJECTIVE: To compare the effectiveness of weight-management medications used to assist with weight loss in real-world clinical practice in the Veterans Health Administration (VHA). DESIGN: Retrospective, multicenter, observational cohort study. DATA SOURCE: National VA Corporate Data Warehouse. PATIENTS: A total of 66,035 VA patients aged 18 years or older with a body mass index of 25 kg/m2 or greater who had an initial fill for a study medication (orlistat [6153 patients], phentermine [304 patients], lorcaserin [298 patients], or phentermine-topiramate extended release [233 patients]) or participation in the VA's MOVE! weight-management program with at least three total visits in a clinic coded as a MOVE clinic in the subsequent 24 weeks (59,047 patients) between January 1, 2012, and July 1, 2016. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the percentage change in weight from baseline to at least 20 weeks or later (i.e., closest weight to 6 months). Secondary outcomes were difference in the percentage of weight loss at 12 and 36 weeks; changes in blood pressure, hemoglobin A1c , high-density and low-density lipoprotein cholesterol and triglyceride levels; and percentage of patients who achieved at least a 5% and 10% weight loss at 6 months from baseline in each group after at least 20 weeks. For the primary outcome, the percentage decrease in weight from baseline after at least 20 weeks in the lorcaserin, phentermine-topiramate, phentermine, orlistat, and MOVE! groups were 3.6%, 4.1%, 3.6%, 2.1%, and 1.6%, respectively (phentermine-topiramate group vs. MOVE! group, p<0.05). Achievement of at least a 5% weight loss after at least 20 weeks differed significantly among groups, ranging from 26.2% for the MOVE! Program only group to 40.3% for patients in the phentermine-topiramate group. CONCLUSION: In the VA population, the effectiveness of four available weight-management medications was similar. Patients receiving phentermine-topiramate had a greater proportion of weight loss after at least 20 weeks compared with those solely enrolled in the VA's MOVE! weight-management program.

Cardiovascular safety of low-dose fenfluramine in Dravet syndrome: a review of its benefit-risk profile in a new patient population.

OBJECTIVE: Dravet syndrome (DS) is a rare, treatment-resistant epilepsy syndrome for which current treatment regimens are often ineffective. Fenfluramine is currently in development for treatment of DS, based on reports in the 1980s and 1990s of its anti-epileptic activity in pediatric patients with intractable epilepsy. However, fenfluramine was withdrawn from global markets in 1997 following reports of its association with pulmonary hypertension and heart valve disease in adult patients treated for obesity. This review was conducted to assess cardiac safety of fenfluramine when used at lower doses for treatment of DS. METHODS: Pubmed was searched for clinical studies of fenfluramine in obese adults who reported incidence of heart valve disease. These data were reviewed against published results from Belgian patients with DS who have been treated with low-dose fenfluramine for up to 28 years. RESULTS: Nine controlled studies of fenfluramine and related compounds (dexfenfluramine and/or phentermine) which assessed incidence and severity of cardiac valve disease in 3,268 treated patients and 2,017 control subjects have been reported. Mild or greater aortic valve regurgitation was found in 9.6% of treated patients compared with 3.9% of control subjects, and moderate or greater mitral valve regurgitation was found in 3.1% of treated patients and 2.5% of control subjects. Nineteen DS patients have been treated for up to 28 years with 10-20 mg/day fenfluramine, with no clinical signs or symptoms of cardiac valve disease or pulmonary hypertension. Slight and clinically unimportant changes in valve structure have been seen on echocardiography in five patients at some time during the observation period. CONCLUSIONS: A different benefit-risk relationship appears to be emerging when fenfluramine is used at low doses for extended periods in young patients with DS. Continued cardiac assessments during ongoing Phase 3 clinical trials will provide additional safety information for this potential new and effective treatment.

Coadministration of lorcaserin and phentermine for weight management: A 12-week, randomized, pilot safety study.

OBJECTIVE: To assess the short-term tolerability of lorcaserin alone or with two dose regimens of phentermine. METHODS: This was a 12-week, randomized, double-blind, pilot safety study of N = 238 nondiabetic patients with obesity or overweight with ≥1 comorbidity randomized to lorcaserin 10 mg twice daily (BID; LOR BID) alone or with phentermine 15 mg once daily (QD; LOR BID+PHEN QD) or 15 mg twice daily (LOR BID+PHEN BID). Patients reporting ≥ 1 of 9 potentially serotonergic adverse events (AEs), mean weight loss (WL), and ≥5% WL are reported. RESULTS: N = 238 were randomized, and N = 235 were treated. N = 94 reported potentially serotonergic AEs: 37.2% LOR BID, 42.3% LOR BID+PHEN QD, and 40.5% LOR BID+PHEN BID. AEs leading to discontinuation were reported approximately twice as often in the LOR BID+PHEN BID group versus the LOR BID group. Mean WL was 3.5 kg/3.3%, 7.0 kg/6.7%, and 7.6 kg/7.2% for LOR BID, LOR BID+PHEN QD, and LOR BID+PHEN BID, respectively. At least 5% WL was achieved by 28.2% LOR BID, 59.0% LOR BID+PHEN QD (P = 0.0002 vs. LOR BID), and 70.9% LOR BID+PHEN BID (P < 0.0001 vs. LOR BID) patients. CONCLUSIONS: Phentermine added to lorcaserin enhanced short-term weight loss but did not increase incidence of potentially serotonergic AEs; however, phentermine twice daily increased discontinuation compared to both lorcaserin alone and lorcaserin plus phentermine once daily.

Cardiometabolic Disease Staging Predicts Effectiveness of Weight-Loss Therapy to Prevent Type 2 Diabetes: Pooled Results From Phase III Clinical Trials Assessing Phentermine/Topiramate Extended Release.

OBJECTIVE: To assess the ability of medication-assisted weight loss to prevent diabetes as a function of the baseline weighted Cardiometabolic Disease Staging (CMDS) score. RESEARCH DESIGN AND METHODS: We pooled data from 3,040 overweight and obese participants in three randomized controlled trials-CONQUER, EQUIP, and SEQUEL-assessing efficacy and safety of phentermine/topiramate extended release (ER) for weight loss. In these double-blind phase III trials, overweight/obese adult patients were treated with a lifestyle intervention and randomly assigned to placebo versus once-daily oral phentermine/topiramate ER. The weighted CMDS score was calculated using baseline quantitative clinical data including waist circumference, blood glucose, blood pressure, and blood lipids. Incident diabetes was defined based on serial measures of fasting glucose, 2-h oral glucose tolerance test glucose, and/or HbA1c. RESULTS: The absolute decrease in 1-year diabetes incidence rates in subjects treated with medication versus placebo was greatest in those with high-risk CMDS scores at baseline (10.43-6.29%), intermediate in those with moderate CMDS risk (4.67-2.37%), and small in the low-risk category (1.51-0.67%). The number of participants needed to treat to prevent one new case of diabetes over a 56-week period was 24, 43, and 120 in those with baseline CMDS scores of ≥60, 30-59, and 0-29, respectively. CONCLUSIONS: Numbers needed to treat to prevent one case of type 2 diabetes are markedly lower in patients with high-risk scores. CMDS can be used to quantify risk of diabetes in overweight/obese individuals and predict the effectiveness of weight-loss therapy to prevent diabetes.

Coadministration of Canagliflozin and Phentermine for Weight Management in Overweight and Obese Individuals Without Diabetes: A Randomized Clinical Trial.

OBJECTIVE: To assess the efficacy and safety of coadministration of canagliflozin (CANA) and phentermine (PHEN) compared with placebo (PBO) and CANA or PHEN monotherapies in individuals who were overweight and obese without type 2 diabetes. RESEARCH DESIGN AND METHODS: This 26-week, phase 2a, randomized, double-blind, PBO-controlled, multicenter, parallel-group study enrolled individuals who were obese or overweight without type 2 diabetes (N = 335, aged 18-65 years, BMI ≥30 to <50 kg/m2 or BMI ≥27 to <50 kg/m2 with hypertension and/or dyslipidemia). Participants were randomized (1:1:1:1) to receive PBO, CANA 300 mg, PHEN 15 mg, or coadministration of CANA 300 mg and PHEN 15 mg (CANA/PHEN) orally once daily. The primary end point was percent change in body weight from baseline to week 26; key secondary end points were the proportion of participants achieving weight loss ≥5% and change from baseline in systolic blood pressure. RESULTS: CANA/PHEN provided statistically superior weight loss from baseline versus PBO at week 26 (least squares mean difference -6.9% [95% CI -8.6 to -5.2]; P < 0.001). CANA/PHEN also provided statistically superior achievement of weight loss ≥5% and reduction in systolic blood pressure compared with PBO. CANA/PHEN was generally well tolerated, with a safety and tolerability profile consistent with that of the individual components. CONCLUSIONS: CANA/PHEN produced meaningful reductions in body weight and was generally well tolerated in individuals who were overweight or obese without type 2 diabetes. Further studies are warranted to evaluate potential use of this combination for long-term weight management.

Safety assessment of combination therapies in the treatment of obesity: focus on naltrexone/bupropion extended release and phentermine-topiramate extended release.

INTRODUCTION: Few studies on combination therapies for the treatment of obesity had been conducted until recently, when two fixed-dose combinations, bupropion-naltrexone ER fixed-dose combination and phentermine-topiramate ER titrated-dose combinations were evaluated in clinical studies that ultimately led to FDA approval. Areas covered: In this review, we discuss safety concerns about both combinations, the rationale and history of combination therapies for obesity (including phentermine plus fenfluramine), and possible future new combinations. Expert opinion: Combination therapies are a promising new area in obesity treatment, similar to what occurs with diabetes and hypertension. Safety assessment is highly important due to the high number of potential users on a chronic basis.

Effects of a meal replacement system alone or in combination with phentermine on weight loss and food cravings.

OBJECTIVE: To examine the effects of phentermine combined with a meal replacement program on weight loss and food cravings and to investigate the relationship between food cravings and weight loss. METHODS: In a 12-week randomized, double-blind, placebo-controlled clinical trial, 77 adults with obesity received either phentermine or placebo. All participants were provided Medifast® meal replacements, were instructed to follow the Take Shape for Life® Optimal Weight 5&1 Plan for weight loss, and received lifestyle coaching in the Habits of Health program. The Food Craving Inventory and the General Food Cravings State and Trait Questionnaires were used to measure food cravings. RESULTS: The phentermine group lost 12.1% of baseline body weight compared with 8.8% in the placebo group. Cravings for all food groups decreased in both groups; however, there was a greater reduction in cravings for fats and sweets in the phentermine group compared with the placebo group. Percent weight loss correlated significantly with reduced total food cravings (r = 0.332, P = 0.009), cravings for sweets (r = 0.412, P < 0.000), and state food cravings (r = 0.320, P = 0.007). CONCLUSIONS: Both phentermine combined with a meal replacement program and meal replacements alone significantly reduced body weight and food cravings; however, the addition of phentermine enhanced these effects.

Answers to Clinical Questions in the Primary Care Management of People with Obesity: Pharmacologic Management.

The recent approval of liraglutide, lorcaserin, naltrexone/bupropion extended-release, and phentermine/topiramate extended-release, brings the number of medications for long-term weight loss to 5 (including orlistat). Indicated for the treatment of patients with overweight (body mass index [BMI] ≥27 kg/m2 with ≥1 weight-related comorbidity) or obesity (BMI ≥30 kg/m2), these medications provide new opportunities to address this burgeoning health problem.

Pharmacotherapy in Conjunction with a Diet and Exercise Program for the Treatment of Weight Recidivism or Weight Loss Plateau Post-bariatric Surgery: a Retrospective Review.

BACKGROUND: Bariatric surgery is an effective therapeutic option for management of obesity. However, weight recidivism (WR) and weight loss plateau (WLP) are common problems. We present our experience with the use of two pharmacotherapies in conjunction with our standard diet and exercise program in those patients who experienced WR or WLP. METHODS: From June 2010 to April 2014, bariatric surgery patients who experienced WR or WLP after undergoing Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB), and who were treated with phentermine (Ph) or phentermine-topiramate (PhT), were reviewed retrospectively. Generalized estimating equations were used to compare patient weights through 90 days between initial surgery type and medication type. Patient weights, medication side effect, and co-morbidities were collected during the first 90 days of therapy. RESULTS: Fifty-two patients received Ph while 13 patients received PhT. Overall, patients in both groups lost weight. Among those whose weights were recorded at 90 days, patients on Ph lost 6.35 kg (12.8% excess weight loss (EWL); 95% confidence interval (CI) 4.25, 8.44) and those prescribed PhT lost 3.81 kg (12.9% EWL; CI 1.08, 6.54). Adjusting for baseline weight, time since surgery, and visit through 90 days, patients treated with Ph weighed significantly less than those on PhT throughout the course of this study (1.35 kg lighter; 95% CI 0.17, 2.53; p = 0.025). There were no serious side effects reported. CONCLUSIONS: Phentermine and phentermine-topirimate in addition to diet and exercise appear to be viable options for weight loss in post-RYGB and LAGB patients who experience WR or WLP.

Paradoxical topiramate-induced hyperphagia successfully treated with phentermine in a woman with migraine.

We report a 49-year-old female migraineur who experienced paradoxical hyperphagia and concurrent intrusive food thoughts leading to rapid weight gain and a substantial increase in waist circumference. A significant reduction in migraine frequency was also observed during topiramate treatment, a widely used migraine prophylactic agent which is generally associated with weight loss. Withdrawal of topiramate saw appetite return to baseline levels, however, migraine frequency was again increased. Topiramate was reinitiated in combination with phentermine, a drug indicated for weight management, without reoccurrence of adverse effects. Migraine control was maintained and progressive weight loss ensued. Combination treatment with phentermine may be a useful strategy should other patients experience this adverse reaction while gaining therapeutic anti-migraine benefit from topiramate.

Cost-Effectiveness Analysis of Qsymia for Weight Loss.

BACKGROUND: Phase 3 clinical trial results reveal that Qsymia is a clinically effective long-term treatment for obesity, but whether this treatment is cost-effective compared to a diet and lifestyle intervention has yet to be explored. OBJECTIVE: To quantify the incremental cost-effectiveness of Qsymia (phentermine and topiramate extended-release) for health-related quality of life improvements. STUDY DESIGN AND METHODS: Estimates are based on cost and quality of life outcomes from a 56-week, multicenter, placebo-controlled, phase 3 clinical trial undertaken in 93 health centers in the US. Participants were overweight and obese adults (aged 18-70 years) with a body-mass index of 27-45 kg/m(2) and two or more comorbidities (hypertension, dyslipidemia, diabetes or pre-diabetes or abdominal obesity). The intervention was diet and lifestyle advice plus the recommended dose of Qsymia (phentermine 7.5 mg plus topiramate 46.0 mg) vs. control, which included diet and lifestyle advice plus placebo. The study was from the payer perspective. Costs included the prescription cost, medication cost offsets and physician appointment costs. Effectiveness was measured in terms of quality-adjusted life years gained (QALYs). The main outcome measure was incremental cost per QALY gained of the intervention relative to control. RESULTS: Our base-case model, in which participants take Qsymia for 1 year with benefits linearly decaying over the subsequent 2 years, generates an incremental cost-effectiveness ratio (ICER) of $48,340 per QALY gained. Using the base-case assumptions, probabilistic sensitivity analyses reveal that the ICER is below $50,000 per QALY in 54 % of simulations. However, results are highly dependent on the extent to which benefits are maintained post medication cessation. If benefits persist for only 1 year post cessation, the ICER increases to $74,480. CONCLUSION: Although base-case results suggest that Qsymia is cost-effective, this result hinges on the time on Qsymia and the extent to which benefits are maintained post medication cessation. This should be an area of future research.