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Semaglutide lowered the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke Phentermine acts to reduce appetite through increasing norepinephrine in the hypothalamus. Topiramate may reduce appetite through its effect on GABA receptors. The patients in these two studies had higher risk profiles due to excess weight. This weight loss is larger than observed in clinical trials with single drugs Improvements in BP, glycemic measures, HDL cholesterol, and triglycerides occurred with both the recommended and the top doses of the medication in these trials , Improvements in risk factors were related to the amount of weight loss.

In patients with OSA, this combination reduced the severity of symptoms Glaucoma is a rare side effect of topiramate, and the drug is contraindicated in glaucoma. Topiramate is a carbonic anhydrase inhibitor that often produces tingling in the fingers and may change the taste for carbonated beverages. Other potential issues include risk of kidney stones associated with topiramate and increased heart rate in patients susceptible to phentermine. Bupropion is approved as a single agent for depression and for smoking cessation. It reduces food intake by acting on adrenergic and dopaminergic receptors in the hypothalamus.

It has a modest effect on weight loss. In one study , weight loss at 56 weeks was 5. Treatment also improved waist circumference, fasting glucose, fasting insulin, homeostasis assessment model of insulin resistance HOMA-IR , and HDL cholesterol, but there was a transient increase in BP.

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The study also reported significant improvements in weight, waist circumference, insulin, homeostatic model assessment of insulin resistance, HDL cholesterol, triglycerides, and quality of life. In a third study, weight loss at week 56 was 6. As in the other studies, there were improvements in cardiometabolic risk markers, weight-related quality of life, and control of eating. There was also improvement in triglycerides and HDL cholesterol compared with placebo.

Because bupropion increases pulse and both bupropion and naltrexone increase BP, an ongoing study is examining cardiovascular outcomes There are no head-to-head comparisons of these medications.

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The inclusion criteria and background lifestyle interventions differed across studies, so we must interpret results with caution. All five agents were associated with significantly greater weight loss at 1 year than placebo. We group the sympathomimetic drugs benzphetamine, diethylpropion, phendimetrazine, and phentermine together, because they are noradrenergic drugs that the FDA tested and approved before The U.

Drug Enforcement Agency classifies phentermine and diethylpropion as schedule IV drugs and benzphetamine and phendimetrazine as schedule III drugs. The FDA approved phentermine as a single agent in , and it remains the most commonly prescribed drug for weight loss in the United States There are few current data to evaluate its long-term efficacy.

In another 6-month study of phentermine, weight loss was 5. Finally, a study from Korea reported that after 12 weeks, mean weight loss for phentermine was 8.


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Weight loss with phentermine may not be greatly enhanced by increasing doses beyond 15 mg Phentermine is part of a group of drugs called sympathomimetic drugs. These drugs produce central excitation, manifested as dry mouth, insomnia, or nervousness. This effect is most obvious shortly after the drug is started and wanes substantially with continued use. Sympathomimetic drugs may also increase heart rate and BP.

The prescribing information usually recommends that the drugs not be given to individuals with a history of CVD — Lacking good quantitative measures of the effects of sympathomimetic drugs on heart rate and pulse, we recommend caution in prescribing drugs in this group. According to the Endocrine Society Guidelines , clinicians should not prescribe sympathomimetic drugs to persons with a history of CVD and elevated BP.

Those guidelines do not require that patients fail lifestyle therapy before clinicians prescribe medications. For patients who are overweight or obese, the Endocrine Society clinical practice guidelines on obesity pharmacotherapy recommended that providers consider body weight when prescribing medications for other chronic health conditions, so that at-risk patients can avoid medications that promote weight gain. The guideline recommends that patients use medications that are weight neutral or associated with weight loss.

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In managing patients with obesity, the guideline also advises that providers review medications at every visit and discuss weight effects with patients, so that patients at risk for weight gain can share in the decision process when choosing medications. According to the Awareness, Care and Treatment in Obesity Management study , there are a number of misconceptions regarding obesity shared by providers and patients alike, specifically that obesity is not a disease, that patients have the primary responsibility for their problem and for its treatment, that prevention is more important than treatment, and that the risks of treatment should be low.

At present, the FDA has approved nine agents five for long-term use and four for short-term use. For newer drugs, the time since approval of these medications is too short to know whether and how they will be used.

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However, older data which predate the current medication landscape indicate there are some serious concerns about how diet medications are used, such as: patients using prescription weight-loss pills who do not meet the BMI criterion for these medications; family, friends, and other nonphysicians providing medications; the use of nonprescription diet products; using pills after they were withdrawn from the market; low 1-year persistent use rates; and co-using narcotic and antidepressants 35 , , , This legislation helped undercut the credibility of legitimate weight-management practices by allowing the promotion of agents that are often unsafe, ineffective, and have unproven health claims.

As long as the claim is not for disease treatment per se , and products are generally recognized as safe, they can be promoted for health claims. These agents are regulated by the U. Federal Trade Commission but not by the FDA, and thus they do not undergo the rigorous testing and review exercised by the FDA when it approves pharmaceutical preparations for patients who are overweight or obese.

Blanck et al. Pillitteri et al.

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Many respondents thought that dietary supplements are safer than prescription drugs, and many overestimated the degree of regulatory screening of these products. Clinicians should be aware and knowledgeable about these products when they begin discussing weight management with patients, since patients have likely taken them or may currently be taking them.

Table 10 provides a list of herbal and complementary medications and treatments that claim to improve weight loss. Evidence to support the effectiveness for weight loss or the safety of these preparations is usually nonexistent. Moreover, variability in the composition of these products adds an additional uncertainty to their use. We thus think that the public would be better served if the dietary supplements were held to a higher standard and were overseen by the FDA.


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Effective drugs to treat obesity have been slow to arise, but efforts are still underway to develop novel, effective, and transformative medications that would have the effect on treating obesity that statins had for high cholesterol or thiazides had for hypertension Surgical strategies including the use of medical devices for the purpose of inducing and maintaining clinically significant weight loss have emerged and evolved during the last 50 years.

Sleeve gastrectomy SG is the most common procedure We list the three most common surgical procedures in Fig. The three most commonly performed bariatric surgical operations. See Nielsen et al. Evidence now indicates that that some of these bariatric procedures which were intended to either physically limit the ingestion of food or produce malabsorption of energy-containing nutrients actually produce durable weight loss and health benefits by altering metabolic processes, reducing appetite, and inducing satiety early after meal ingestion.

The lack of gastrojejunal anastomosis has theoretic benefits, such as reducing the risk of micronutrient deficiencies and peptic ulcer disease. Although some restriction of food intake may occur, gastric emptying is accelerated. Most of the stomach is therefore disconnected but not excised from the alimentary stream. The small gastric pouch is the restrictive component of this procedure. RYGB permits ingested food to pass directly from the esophagus through the small stomach pouch and proceed directly into the jejunum, with little or no gastric or duodenal phase of digestion, because food never enters the body of the stomach or the duodenum.

RYGB became a predominant weight-loss procedure in the s and is used worldwide today. The development and demonstration of the safety and efficacy of minimally invasive laparoscopic techniques, the recognition of severe obesity as a disease, and the health benefits of bariatric surgery have led to a progressive increase in the number of gastric bypass procedures performed , , , LAGB constricts the upper stomach by placing a mechanical device encircling the stomach just beyond the gastroesophageal junction, thus creating a small 30 to 60 mL pouch.

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The tightness of the band is adjusted by inflating a linear balloon fixed within the wall of the band. The balloon is connected to a subcutaneous port, so clinicians can tighten the band via a relatively simple percutaneous injection procedure. The band is intended to reduce the amount of food consumed An anastomosis between the proximal duodenum and bypassed intestine creates a degree of malabsorption of nutrients. This procedure is infrequently performed because of a relatively high incidence of short-term and long-term complications, including micronutrient deficiencies In this procedure, leads are placed about the vagal trunks at the diaphragm to produce intermittent vagal blockade.

Weight loss occurs by reducing appetite and inducing early satiety. The intermittent blockade is designed to avoid the neural adaptation that occurred with truncal vagatomy for peptic ulcer disease. Weight loss, although modest, is superior to sham-treated controls yet less successful than conventional surgical procedures, such as SG and gastric bypass Despite a better safety profile than adjustable banding, intermittent vagal blockade has limited efficacy. This coupled with adverse events make it a less desirable intervention for resolving obesity and associated comorbidities Several devices, placed either by gastrointestinal endoscopy or suturing procedures, have become available.

The FDA approved two gastric balloons in and another in Clinicians can fill the Orbera intragastric balloon system with to mL of saline. The ReShape integrated dual balloon system contains two connected, saline-filled balloons.