Medications that Can Cause Weight Gain Derrick Cetin, D.O. Obesity Medicine Clinical Assistant Professor Dept. of Medicine Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Bariatric and Metabolic Institute Digestive Disease Institute 9/15/18
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Medications that Can Cause Weight Gain · - weight gain usually observed in the first 3 months of treatment - women > men • Carbamazepine- weight gain to a lesser extent than valproate
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Medications that Can Cause Weight Gain
Derrick Cetin, D.O.Obesity Medicine
Clinical Assistant Professor Dept. of Medicine Cleveland Clinic Lerner College of Medicine of Case
Western Reserve UniversityBariatric and Metabolic Institute
Digestive Disease Institute9/15/18
Drug-Induced Weight Gain, Audience Should Know:
• A possible serious side effect of many commonly used drugs used for a variety of disease states
• Leads to exacerbation of co-morbid conditions related to obesity due to associated weight gain
• While some medications are more common than others to cause weight gain, not all individuals gain weight from every drug that has weight gain listed as a side effect
• In many cases if possible, substitute an alternative medication to treat the same condition that is weight neutral or weight negative
Case Study
55 year old Caucasian female referred by bariatric surgeon for medical evaluation of weight regain. S/P RYGB 2003 with 125 lbs weight loss. Regained her weight and now at highest post operative weight. Her current weight is 285 lbs with a BMI of 55 kg/m^2.Concerns that she has been noncompliant with her vitamin, mineral supplementation and dietary recommendations. She has not been able to exercise regularly due to a back injury. T2DM, HTN, and major depressive disorder.
Approach to Post Operative Bariatric Surgery Weight Regain
Post Operative Weight Regain
Anatomical PhysiologicalBehavioral
Psychosocial
Approach to Post Operative Bariatric Surgery Weight Regain
Post Operative Weight Regain
Anatomical Physiological BehavioralPsychosocial
Physiological Causes of Weight Gain
• Pregnancy• Menopause• Smoking cessation• Endocrine disease• Hypothyroidism• Cushing's disease• Adaptations: hypoleptinemia, energy efficiency, gut hormones (PYY)• Weight-gain promoting medications
Physiological Causes of Weight Gain
• Pregnancy• Menopause• Smoking cessation• Endocrine disease• Hypothyroidism• Cushing's disease• Adaptations: hypoleptinemia, energy efficiency, gut hormones (PYY)• Weight-gain promoting medications
Clinical Practice Guidelines for the Use of Atypical Antipsychotic Medications
• Body weight at 4 week intervals and the quarterly• Fasting plasma glucose at baseline, 12 weeks, and annually• Lipid profile at baseline, 12 weeks, and every 5 years• Waist circumference at baseline and annually
Clinical Pharmacology & Therapeutics. 2011 Apr 11
Anti-epileptics (AEDs) and Weight Gain
• Valproate- weight reported in the range of 5-49 kg
- weight gain usually observed in the first 3 months of treatment- women > men
• Carbamazepine- weight gain to a lesser extent than valproate
• Gabapentin- least weight gain of AEDs
Mechanism of Anti-epileptics (AEDs) Associated Weight Gain
• Mechanisms by which AEDs cause weight gain are not fully understood and controversial
• It is likely that the weight change may have some underlying genetic underpinning
Measurements of body weight before initiation of valproic acid therapy should be done as part of the monitoring of patients with epilepsy to detect changes before there are serious adverse consequences; an increase of 2 kg of body weight after 1 month of treatment should imply considerations to change antiepileptic drug therapy.
Obes Rev. 2011 May; 12(5): e 32-43
Antidepressant Medications and Weight Gain WEIGHT GAIN ASSOCIATE WITH USE
Drug Class/Type(and Potential Related Weight Gain)
Common Name Brand Name
Insulin (weight gain differs with type and regimen used)
Insulin lisproInsulin aspartInsulin glulisine
HumalogNovologApidra
Thiazolidinediones (TZDs)Shift in fat distribution from visceral to subcutaneous adipose depots that is associated with improvements in hepatic and peripheral tissue sensitivity to insulin
• Sulfonylureas usually ≤ 5 kg gain during 3-12 months of treatment- increase weight by decreasing amount of glucose excreted in the
urine, leads to storage of glucose as fat• Insulin promotes weight gain by causing the body to retain more calories• TZDs lead to weight gain from fluid retention and SQ fat deposition• Both insulin and sulfonyureas can cause weight gain as a result of
hypoglycemia- promotes overeating to avoid hypoglycemia
Insulin-Associated Weight Gain in Diabetes
Diabetes, Obesity and Metabolism. Volume 9, Issue 6, pages 799-812, 15 Dec 2006
Cardiovascular Medications and Weight Gain
• Some β-blockers
- Propranolol
- Atenolol
- Metoprolol
• Some α-blockers
- Clonidine- mechanism of weight gain from reduced metabolic rate as
a result of decreased sympathetic activity
• Calcium blockers are weight neutral except for flunarizine (sibelium)
J Clin Endocrinol Metab. 2015 Feb; 100(2):342-62
Potential Mechanisms of β-Blocker- Associated Weight Gain
• Reduction in resting energy expenditure• Reduction in the thermic effect of food• Reduction in exercise tolerance• Increase in tiredness• Reduction in nonexercise thermogenesis• Inhibition of lipolysis• Exacerbation of insulin resistance
Sharma AM, et al. Hypertension. 2001; 37: 250-254
Antihistamines and Hypnotics and Weight Gain
• May increase body weight:- Diphenhydramine
• May have limited effects on body weight:- Benzodiazepines- Melatonergic hypnotics- Trazadone
Human Immunodeficiency Virus (HIV) Medications and Weight Gain
• 33-75% of patients with HIV infection receiving highly active antiretroviral therapy (HAART) develop a syndrome referred to as lipodystrophy
• All Protease inhibitors (PI) and the Nucleoside Reverse Transcriptase Inhibitors (NRITs), ddi, D4t, AZT linked to lipodystrophy, risk is greater the longer the drug is used, and if older, Caucasian, or overweight/obese
• Characteristic body habitus associated with peripheral wasting of fat in the face, arms, legs and buttocks
• Manifest as lipid redistribution to other areas:- increase in abdominal girth from accumulation of intra-abdominal fat- buffalo hump- enlargement of the breasts
Lipodystrophy a Possible Side Effect of HIV Drugs
• Characteristic body habitus associated with peripheral wasting of fat in the face, arms, legs and buttocks
• Manifest as lipid redistribution to other areas:- increase in abdominal girth from accumulation of intra-abdominal fat- buffalo hump- enlargement of the breasts
Chemotherapies and Weight
• May increase body weight:- Tamoxifen- Cyclophosphamide- Methotrexate- 5- fluorouracil- Aromatase inhibitors- Corticosteroids
Antipsychotic and Anticonvulsant Medications and Weight Gain
J Clin Endocrinol Metab. 2015 Feb; 100(2):342-62
* Only phentermine/topiramate ER is FDA-approved for chronic weight management in patients with BMI 30+ kg/m2 or BMI 27-29.9 kg/m2 with one or more comorbidities
Metformin Prevents Antipsychotic Induced Weight Gain in Adolescents
Klein DJ, et al Am J Psychiatry 2006; 163:2072–2079.
Metformin 850 bid, in addition to program of diet and physical activity, prevented weight gain in adolescents gaining weight on antipsychotic agents
Drug Class/Type(and Potential Related Weight Gain)
Drugs That Cause Weight Gain and Some Alternatives
• Patients with obesity and T2DM requiring insulin therapy, suggest adding at least one of the following: metformin, pramlintide, or GLP-1 receptor agonists to mitigate associated weight gain due to insulin
• The first-line insulin for this type of patient should be basal insulin (this is preferable to using either insulin alone or insulin with sulfonylurea)
• Recommend the initial insulin therapy strategy consider a preferential trial of basal insulin prior to premixed insulins or combination insulin therapy
J Clin Endocrinol Metab. 2015 Feb; 100(2):342-62
MEDICATIONS WEIGHT GAIN ASSOCIATED WITH USE ALTERNATIVES(WEIGHT REDUCTING IN PARENTHESES)*
Antipsychotic and Anticonvulsant Medications and Weight Gain
J Clin Endocrinol Metab. 2015 Feb; 100(2):342-62
* Only phentermine/topiramate ER is FDA-approved for chronic weight management in patients with BMI 30+ kg/m2 or BMI 27-29.9 kg/m2 with one or more comorbidities
Antidepressant Medications and Weight GainMEDICATIONS WEIGHT GAIN ASSOCIATED WITH USE ALTERNATIVES
* Only naltrexone SR/ bupropion SR combination is FDA-approved for chronic weight management in patients with BMI 30+ kg/m2 or BMI 27 <30 kg/m2 with one or more comorbidities
Lithium Lithium
Antidepressants/mood stabilizers: SSRIs
Fluoxetine? Sertraline? Paroxetine Fluvoxamine
Antidepressants/mood stabilizers: MAOI Phenylzine
Tranylcypromine
J Clin Endocrinol Metab. 2015 Feb; 100(2):342-62
Bupropion is the only antidepressant associated with long-term weight loss, but only in nonsmokers, according to a new retrospective cohort study published in the Journal of Clinical Medicine, April 13, 2016
Antidepressant Medications and Weight GainMEDICATIONS WEIGHT GAIN ASSOCIATED WITH USE ALTERNATIVES
* Only naltrexone SR/ bupropion SR combination is FDA-approved for chronic weight management in patients with BMI 30+ kg/m2 or BMI 27 <30 kg/m2 with one or more comorbidities
Lithium Lithium
Antidepressants/mood stabilizers: SSRIs
Fluoxetine? Sertraline? Paroxetine Fluvoxamine
Antidepressants/mood stabilizers: MAOI Phenylzine
Tranylcypromine
J Clin Endocrinol Metab. 2015 Feb; 100(2):342-62
Bupropion is the only antidepressant associated with long-term weight loss, but only in nonsmokers, according to a new retrospective cohort study published in the Journal of Clinical Medicine, April 13, 2016
Metformin
• May help treat complications of other concurrent drug treatments:- Antipsychotic-related weight gain- Human immunodeficiency virus (HIV) protease inhibitor-associated abnormalities
( i.e., HIV lipodystrophy)
Conclusion
• Weight promoting medications are one of the many modifiable environmental & lifestyle factors to consider when evaluating a patient for weight gain
• Drug-induced weight gain is a serious side effect of many commonly used medications leading to noncompliance with therapy and exacerbation of comorbid conditions related to obesity
• If possible discontinue or change weight gain-promoting medications to an alternative that has a weight neutral or a weight negative effect
• An exception, is if a medication is specifically indicated for an underlying condition, should be continued regardless of the effects on weight gain