Episode 106 - Weight Loss Meds

Episode 106: Weight Loss Meds. 

Anti-obesity medications are FDA-approved drugs to support your patient’s efforts to lose weight. It is important for primary care providers to learn about these medications to continue fighting against obesity in our communities.

Introduction: Obesity is a chronic disease.
By Hector Arreaza, MD. 

Obesity has all the characteristics of a chronic disease. Let’s use our imagination and think about a patient with hypertension, for example. Let’s imagine you are the doctor or Mr. Lee. He is 45 years old and his blood pressure has been persistently high, around 150/100, even after lifestyle modifications. You decide to start chlorthalidone 25 mg and Mr. Lee takes chlorthalidone every day. Four weeks later you see Mr. Lee again and you review his labs with him. He has normal renal function and normal electrolytes. His blood pressure is now 119/75. He is feeling great and reports no side effects to chlorthalidone. Would you stop the medication at this time? Think about it. The most obvious answer is NO, you will not stop chlorthalidone. Today you will listen to a discussion about anti-obesity medications, common indications, contraindications, cautions, and more. We will learn that obesity requires chronic treatment with medications just like any other chronic disease. I hope you enjoy it.

This is the Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it’s sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. 

This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.

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Weight Loss Meds. 
By Sapna Patel, MS4; and Danish Khalid, MS$. Ross University School of Medicine. Moderated by Hector Arreaza, MD.

 

S: Hello and welcome back to our nutrition series! If you haven't already listened to our previous episodes, pause this and make sure to give them a listen. We have talked about physical activity, meal plans, and intermittent fasting. Today we are going to talk about the clinical management of obesity, specifically the pharmacotherapy that is used. We will divide these drugs into drugs that reduce food intake primarily acting on the CNS, drugs that reduce fat absorption and medications that are associated with weight gain.

 

D: Can anyone who is considered obese take medications to help them lose weight? Pharmacotherapy should be considered if the patient will be taking the medication in conjunction with the overall weight management program, including changes in eating habits, increased physical activity, and realistic expectations of the medication therapy. Adjuvant pharmacologic treatments should be considered for patients with a BMI >30 kg/m2 or with BMI >27 kg/m2 who have concomitant obesity related diseases.

 

A: You are going to find doctors who are pretty much against anti-obesity drugs, but that’s not my case. 

 

S: Drugs that reduce food intake primarily acting on the CNS: 

Let's start with Phentermine and other sympathomimetic drugs

 

A: Phentermine has been in the market over 60 years and it is well tolerated by most patients. It is effective, expect 5-8 lbs weight loss a month when taken with dietary changes and increased physical activity. The weight loss happens mostly the first 3-6 months when you take anti-obesity medications.

 

S: One of the longest clinical trials of the drugs in this group lasted 36 weeks and compared placebo treatment to treatment with continuous phentermine and intermittent phentermine. Both the continuous and intermittent phentermine therapy produced more weight loss than placebo.

 

D: Other options are Phentermine and topiramate ER which is known as  “Qsymia”. These drugs combine a catecholamine releaser and anticonvulsant respectively.  Topiramate is currently approved by the USFDA as an anticonvulsant for treatment of epilepsy and for prophylaxis of migraine headaches. Weight loss was seen as an unintentional side effect during clinical trials for epilepsy.The mechanism responsible for this is thought to be mediated through the modulation of GABA receptors, inhibition of carbonic anhydrase and antagonism of glutamate to reduce food intake The common adverse effects include cognitive impairment, paresthesia, and increased risk for kidney stones. Topiramate is also a teratogenic drug, so patients need to be in a good birth control to take it. It causes cleft palate in the fetus.The 2 phase-III trials called EQUIP and CONQUER, both 1 year randomized  placebo-controlled double-blinded clinical trials, 3 different strengths of a once-a day formulation were tested: full strength dose (15 mg of phentermine and 92 mg of topiramate ER), mid-dose (7.5mg of phentermine and 92 mg topiramate ER) and low dose (3.75mg of phentermine and 23 mg of topiramate ER). Subjects  randomized to the full strength dose in EQUIP and CONQUER trials lost an average of 10.9% and 9.8% body weight in 1 year compared to 1.6% and 1.2% loss for placebo subjects respectively. Significant improvement in fasting glucose, insulin, Hemoglobin A1C and lipid profile were seen.Due to the dose dependent side effects of the medications an initial dose of 3.75/23 mg is prescribed daily for the first 14 days then increased to 7.5/23mg daily. These patients should be re-evaluated after 3 months. If 3% weight loss is not achieved by that time, either discontinue or escalate the dose to 15/92mg for 12 weeks.

 

S: Drugs that reduce fat absorption:

Orlistat. What is orlistat? Well it's a selective inhibitor of pancreatic lipase that reduces the intestinal digestion of fat. The mean weight loss when compared to a placebo was 2.51kg at 6 months and 2.75kg at 12 months.

 

A: It is one of the few anti-obesity medications approved to be used in children 12 years and older.

 

D: GLP-1 Receptor Agonist (-glutide): 

Semaglutide and Liraglutide - Only two that have been approved for treatment of obesity. A 20-week randomized trial, comparing Liraglutide, placebo, and orlistat, showed that patients assigned to liraglutide lost significantly more weight than those assigned to both. When compared to placebo, those on liraglutide lost a mean weight loss of 2.8 kg. Whereas compared to orlistat lost an average of 5.8kg, however this was on the higher doses of liraglutide. A 56-weeks trial, comparing liraglutide with placebo, showed a mean weight loss was significantly greater in the liraglutide group (8.0 kg vs 2.6 kg). Furthermore, those who initially lost weight with diet and exercise, a greater proportion of those taking liraglutide maintained the weight loss.  Similarly, clinical trials favored semaglutide, with a weight loss greater in the semaglutide group versus placebo. For both, weight loss occurred in patients with and without diabetes.

 

Note: Semaglutide: once a week. Helps induce weight loss. Liraglutide: daily. 

 

A: We dedicated a whole episode on Semaglutide and another whole episode on Tirzepatide. Tirzepatide (dual agonist: GLP-1 and GIP) seems promising for weight loss and it is likely to be approved soon for obesity treatment. So, when do we discontinue anti-obesity medications? We can ask the same question for other chronic diseases: When do we stop medication for hypertension or diabetes? When we have a patient is unable to keep their weight off, we can’t see him/her as someone who has lost their motivation to keep their weight off. Really what’s happened is that their hormones have changed in a way that is promoting weight gain and it’s very hard to lose weight. We should be at the patient’s side to fight it off.

 

Conclusion: Now we conclude our episode number 106 “Weight Loss Meds.” Phentermine is the most widely used anti-obesity medication. It is a stimulant, and it is a safe and effective medication for most patients who are fighting obesity. Make sure you learn the contraindication, side effects, and precautions when you prescribe it. Also, learn about other meds that are very effective, including GLP-1 receptor agonists, and your patients will thank you. This week we thank Hector Arreaza, Danish Khalid, and Sapna Patel. Audio by Sheila Toro.

Thanks for listening to Rio Bravo qWeek Podcast. If you have any feedback, contact us by email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week! 

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References: 

Perreault, L., Apovian, C. (2021). Obesity in adults: Overview of management. Pi-Sunyer,  F.X., Seres, D., & Kunins, L. (Eds.) Uptodate. Available from: https://www-uptodate-com.rossuniversity.idm.oclc.org/contents/obesity-in-adults-overview-of-management?search=weight%20loss%20medications&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2

 

Perreault, L. (2022). Obesity in adults: Drug therapy. Pi-Sunyer,  F.X., & Kunins, L. (Eds.) Uptodate. Available from: https://www-uptodate-com.rossuniversity.idm.oclc.org/contents/obesity-in-adults-drug-therapy?search=weight%20loss%20medications&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1

 

Dungan, K., DeSantis, A. (2022) Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus. Nathan, D.M., & Mulder, J.E. (Eds.) Uptodate. Available from: https://www-uptodate-com.rossuniversity.idm.oclc.org/contents/glucagon-like-peptide-1-based-therapies-for-the-treatment-of-type-2-diabetes-mellitus?search=glp%201%20receptor%20agonists&source=search_result&selectedTitle=2~97&usage_type=default&display_rank=1

 

Perreault, L., Bessesen, D. (2022). Obesity in adults: Etiologies and risk factors. Pi-Sunyer,  F.X., & Kunins, L. (Eds.) Uptodate. Available from: https://www-uptodate-com.rossuniversity.idm.oclc.org/contents/obesity-in-adults-etiologies-and-risk-factors?search=medication%20associated%20with%20weight%20gain&sectionRank=1&usage_type=default&anchor=H1612312650&source=machineLearning&selectedTitle=1~150&display_rank=1#H1612312650.

 

Royalty-free music used for this episode: Salsa Trap by Caslo, downloaded on July, 20, 2022 from https://freemusicarchive.org/music/caslo/caslo-vol-1/salsa-trap/. Space Orbit by Scott Holmes, downloaded on July, 20, 2022 from https://freemusicarchive.org/music/Scott_Holmes/.