Medications that Can Cause Weight Gain

Transcription

1 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

2 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

3 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.

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5 Approach to Post Operative Bariatric Surgery Weight Regain Post Operative Weight Regain Anatomical Physiological Behavioral Psychosocial

6 Approach to Post Operative Bariatric Surgery Weight Regain Post Operative Weight Regain Anatomical Physiological Behavioral Psychosocial

7 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

8 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

9 CNS drugs Endocrine agents Miscellaneous Atypical antipsychotics eg. olanzapine Anti-epileptics (AEDs) eg. valproate Classification of Drugs That May Lead to Weight Gain Glucocorticoids eg. prednisone Hormonal contraceptives eg. medroxyprogesterone Beta Blockers eg. metoprolol Anti-histamines eg. diphenhydramine Lithium Diabetesagents: Sleep aids eg. zolpidem Antidepressants: Ø Insulin HIV medications Ø Selective Serotonin reuptake inhibitors (SSRIs) eg. paroxitene Ø Sulfonylureas eg. glyburide Chemotherapies Ø Tricyclic agents eg. nortriptyline Ø Others eg. venlafaxine, mirtazapine Ø Thiazolidenediones eg. pioglitazone Common Migraine Medications (prophylaxis) Gynecological medications Leslie, et al. QJM. 2007; 100:

10 May substantially increase body weight: Antipsychotics and Weight Gain May somewhat increase body weight: Variable/neutral effects on body weight: Clozaril (Clozapine) Saphris (Asenapine) Solidan (Amisulpride) Zyprexa (Olanzapine) Thorazine (Chlorpromazine) Abilify (Aripiprazole) Fanapt (Iioperidone) Haldol (Haloperidol) Invega (Paliperidone) Latuda (Lurasidone) Seroquel (Quetiapine) Geodon (Ziprasidone) Resperidol (Resperidone) Obesity Algorithm Obesity Medicine Association. Serdolect (Sertindole) Lithium

11 Significant Weight Gain (³7%) with Antipsychotic Medications 35 Incidence (%) Aripiprazole Ziprasidone Risperidone 6 23 Quetiapine 3 29 Olanzapine Abilify [package insert], Geodon [package insert]. Risperdal [package insert]., Seroquel [package insert]., Zyprexa [package insert] Courtesy of Dr. Caroline Apovian

12 Mechanism(s) of Antipsychotic-Associated Weight Gain Review of the literature indicates that a group of factors are associated with weight gain rather than a single mechanism Coupled with genetic profile, the risk for antipsychotic-induced weight gain is heterogeneous among individuals and specific agents Targets for weight gain include receptor interactions involving serotonin, histamine, dopamine, adrenergic, cannabinoid, and muscarinic receptors CNS Drugs Dec 1; 25 (12):

13 Relative Likelihood of Metabolic Disturbances with Atypical Antipsychotic Medications Medication Weight Gain Glucose Metabolism Abnormalities Dyslipidemia Metabolic Syndrome Amisulpride Low Low Low Aripiprazole Low Low Low Low Clozapine High High High High Melperone Olanzapine High HIgh High High Paliperidone Resperidone Medium Medium-to-low Low Medium Sulpiride Quetiapine Medium Medium-to-low High High Sertindole Low Ziprasidone Low Low Low Low Zotepine Medium Primary Care Diabetes. 2009; 3: Current Diabetes Reports. 2010; 10:

14 Atypical Antipsychotic Medications are associated with weight gain Potential Mechanism 5 HT 2c blockade H1 affinity

15 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 Apr 11

16 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

17 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 May; 12(5): e 32-43

18 Antidepressant Medications and Weight Gain WEIGHT GAIN ASSOCIATE WITH USE Antidepressants/mood stabilizers: tricyclic antidepressants Amitriptyline Doxepin Imipramine Nortriptyline Mirtazapine Antidepressants/mood stabilizers: Bipolar disorder Antidepressants/mood stabilizers: SSRIs SSRI use year or more cause weight gain of about 5 lbs SNRIs cause less long term weight gain Lithium Fluoxetine? Sertaline? Paroxetine Fluvoxamine Antidepressants/mood stabilizers: MAO Inhibitors Phenylzine Tranylcypromine J Clin Endocrinol Metab Feb; 100(2):342-62

19 Why Weight Gain Happens with Antidepressants? Antidepressants work by interacting with muscarinic, acetylcholine, and the histamine receptors; when blocked have a proclivity toward weight gain Tricyclic antidepressants block all these receptors, therefore reliably cause weight gain Paroxetine (paxil) has more anticholinergic activity of all the SSRIs, therefore causes the most weight gain. Mirtazapine (remeron) blocks the histamine receptor and is associated with significant weight gain

20 Diabetes Medications Associated with Weight Gain Drug Class/Type (and Potential Related Weight Gain) Common Name Brand Name Insulin (weight gain differs with type and regimen used) Insulin lispro Insulin aspart Insulin glulisine Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Sulfonylureas (SUs) glypizide glyburide glimepride chlorpropamide tolubutamide Glucotrol Diabeta Micronase Glynase Amaryl Diabinese

21 Diabetes Medications Associated with Weight Gain Drug Class/Type (and Potential Related Weight Gain) Common Name Brand Name Insulin (weight gain differs with type and regimen used) 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 (SUs) Insulin lispro Insulin aspart Insulin glulisine pioglitazone glypizide glyburide glimepride chlorpropamide tolubutamide Humalog Novolog Apidra Actos Glucotrol Diabeta Micronase Glynase Amaryl Diabinese

22 Diabetes Medications Associated with Weight Gain Drug Class/Type (and Potential Related Weight Gain) Common Name Brand Name Insulin (weight gain differs with type and regimen used) Insulin lispro Insulin aspart Insulin glulisine Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Sulfonylureas (SUs) Drugs exert their hypoglycemic effects by stimulating insulin secretion from the pancreatic beta-cell glypizide glyburide glimepride chlorpropamide tolubutamide Glucotrol Diabeta Micronase Glynase Amaryl Diabinese

23 Diabetes Medications and Weight Gain 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

24 Insulin-Associated Weight Gain in Diabetes Diabetes, Obesity and Metabolism. Volume 9, Issue 6, pages , 15 Dec 2006

25 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 Feb; 100(2):342-62

26 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:

27 Antihistamines and Hypnotics and Weight Gain May increase body weight: - Diphenhydramine May have limited effects on body weight: - Benzodiazepines - Melatonergic hypnotics - Trazadone Obesity Algorithm Obesity Medicine Association.

28 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 Obesity Algorithm Obesity Medicine Association

29 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

30 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

31 Chemotherapies and Weight May increase body weight: - Tamoxifen - Cyclophosphamide - Methotrexate - 5- fluorouracil - Aromatase inhibitors - Corticosteroids Obesity Algorithm Obesity Medicine Association.

32 Gynecologic Medications and Weight Gain MEDICATIONS WEIGHTGAIN ASSOCIATED WITH USE ALTERNATIVES (WEIGHT REDUCTING IN PARENTHESES) Oral contraceptives Progestational steroids Hormonal contraceptives containing progestational steroids Barrier methods IUDs Endometriosis treatment Depot leuprolide acetate Surgical treatment J Clin Endocrinol Metab Feb; 100(2):342-62

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34 Cardiovascular Medications and Weight Gain MEDICATIONS WEIGHTGAIN ASSOCIATED WITH USE ALTERNATIVES (WEIGHT REDUCTING IN PARENTHESES) Hypertension medications α-blocker? β-blocker? ACE inhibitors? Calcium channel blockers? Angiotensin-2 receptor antagonists J Clin Endocrinol Metab Feb; 100(2):342-62

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36 Antipsychotic and Anticonvulsant Medications and Weight Gain MEDICATIONS WEIGHTGAIN ASSOCIATED WITH USE ALTERNATIVES (WEIGHT REDUCTING IN PARENTHESES)* Antipsychotics Clozapine Risperidone Olanzapine Quetiapine Haloperidol Perphenazine Quetiapine Ziprasidone Aripiprizole Anticonvulsants Carbamazepine Gabapentin Valproate Lamotrigine? (Topiramate) (Zonisamide) * Only phentermine/topiramate ER is FDA-approved for chronic weight management in patients with BMI 30+ kg/m 2 or BMI kg/m 2 with one or more comorbidities J Clin Endocrinol Metab Feb; 100(2):342-62

37 Metformin Prevents Antipsychotic Induced Weight Gain in Adolescents Metformin 850 bid, in addition to program of diet and physical activity, prevented weight gain in adolescents gaining weight on antipsychotic agents Klein DJ, et al Am J Psychiatry 2006; 163:

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39 Diabetes Medications Associated with Weight Gain and Alternatives Drug Class/Type (and Potential Related Weight Gain) Insulin Common Name Insulin lispro Insulin aspart Insulin glulisine Brand Name Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Alternative Drugs (Weight neutral or may promote weightloss) Sulfonylureas glypizide glyburide glimepride chlorpropamide tolubutamide Glucotrol Diabeta Micronase Glynase Amaryl Diabinese

40 Diabetes Medications Associated with Weight Gain and Alternatives Drug Class/Type (and Potential Related Weight Gain) Insulin Common Name Insulin lispro Insulin aspart Insulin glulisine Brand Name Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Alternative Drugs (Weight neutral or may promote weightloss) Sulfonylureas These drugs exert their hypoglycemic effects by stimulating insulin secretion from the pancreatic beta-cell. glypizide glyburide glimepride chlorpropamide tolubutamide Glucotrol Diabeta Micronase Glynase Amaryl Diabinese

41 Diabetes Medications Associated with Weight Gain and Alternatives Drug Class/Type (and Potential Related Weight Gain) Insulin Common Name Insulin lispro Insulin aspart Insulin glulisine Brand Name Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Alternative Drugs (Weight neutral or may promote weightloss) Sulfonylureas glimepride Amaryl

42 Diabetes Medications Associated with Weight Gain and Alternatives Drug Class/Type (and Potential Related Weight Gain) Insulin Common Name Insulin lispro Insulin aspart Insulin glulisine Brand Name Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Alternative Drugs (Weight neutral or may promote weightloss) metformin (Glucophage, Fortamet, Glumetza, Riomet) Sulfonylureas glimepride Amaryl

43 Diabetes Medications Associated with Weight Gain and Alternatives Drug Class/Type (and Potential Related Weight Gain) Insulin Common Name Insulin lispro Insulin aspart Insulin glulisine Brand Name Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Alternative Drugs (Weight neutral or may promote weightloss) metformin (Glucophage, Fortamet, Glumetza, Riomet) SGLT 2 inhibitors Sulfonylureas glimepride Amaryl

44 Diabetes Medications Associated with Weight Gain and Alternatives Drug Class/Type (and Potential Related Weight Gain) Insulin Common Name Insulin lispro Insulin aspart Insulin glulisine Brand Name Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Alternative Drugs (Weight neutral or may promote weightloss) metformin (Glucophage, Fortamet, Glumetza, Riomet) SGLT 2 inhibitors linagliptin (Tradjenta) saxagliptin (Onglyza) sitagliptin (Januvia) Sulfonylureas glimepride Amaryl

45 Diabetes Medications Associated with Weight Gain and Alternatives Drug Class/Type (and Potential Related Weight Gain) Insulin Common Name Insulin lispro Insulin aspart Insulin glulisine Brand Name Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Alternative Drugs (Weight neutral or may promote weightloss) metformin (Glucophage, Fortamet, Glumetza, Riomet) SGLT 2 inhibitors linagliptin (Tradjenta) saxagliptin (Onglyza) sitagliptin (Januvia) exenatide (Byetta) liraglutide (Victoza) Sulfonylureas glimepride Amaryl

46 Diabetes Medications Associated with Weight Gain and Alternatives Drug Class/Type (and Potential Related Weight Gain) Insulin Common Name Insulin lispro Insulin aspart Insulin glulisine Brand Name Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Alternative Drugs (Weight neutral or may promote weightloss) metformin (Glucophage, Fortamet, Glumetza, Riomet) SGLT 2 inhibitors linagliptin (Tradjenta) saxagliptin (Onglyza) sitagliptin (Januvia) exenatide (Byetta) liraglutide (Victoza) acarbose (Precose, Prandase) Sulfonylureas glimepride Amaryl

47 Diabetes Medications Associated with Weight Gain and Alternatives Drug Class/Type (and Potential Related Weight Gain) Insulin Common Name Insulin lispro Insulin aspart Insulin glulisine Brand Name Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Alternative Drugs (Weight neutral or may promote weightloss) metformin (Glucophage, Fortamet, Glumetza, Riomet) SGLT 2 inhibitors linagliptin (Tradjenta) saxagliptin (Onglyza) sitagliptin (Januvia) exenatide (Byetta) liraglutide (Victoza) acarbose (Precose, Prandase) miglitol (Glyset) Sulfonylureas glimepride Amaryl

48 Diabetes Medications Associated with Weight Gain and Alternatives Drug Class/Type (and Potential Related Weight Gain) Insulin Common Name Insulin lispro Insulin aspart Insulin glulisine Brand Name Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Sulfonylureas glimepride Amaryl Alternative Drugs (Weight neutral or may promote weightloss) metformin (Glucophage, Fortamet, Glumetza, Riomet) SGLT 2 inhibitors linagliptin (Tradjenta) saxagliptin (Onglyza) sitagliptin (Januvia) exenatide (Byetta) liraglutide (Victoza) acarbose (Precose, Prandase) miglitol (Glyset) Pramlintide (Amylin)

49 Diabetes Medications Associated with Weight Gain and Alternatives Drug Class/Type (and Potential Related Weight Gain) Insulin Common Name Insulin lispro Insulin aspart Insulin glulisine Brand Name Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Sulfonylureas glypizide glyburide glimepride chlorpropamide tolubutamide Glucotrol Diabeta Micronase Glynase Amaryl Diabinese Alternative Drugs (Weight neutral or may promote weightloss) metformin (Glucophage, Fortamet, Glumetza, Riomet) SGLT 2 inhibitors linagliptin (Tradjenta) saxagliptin (Onglyza) sitagliptin (Januvia) exenatide (Byetta) liraglutide (Victoza) acarbose (Precose, Prandase) miglitol (Glyset) Pramlintide (Amylin) metformin/pioglitazone (Actoplus Met) glipizide/metformin (Metaglip) glyburide/metformin (Glucovance) glimepiride/metformin

50 Diabetes Medications Associated with Weight Gain and Alternatives Drug Class/Type (and Potential Related Weight Gain) Insulin Common Name Insulin lispro Insulin aspart Insulin glulisine Brand Name Humalog Novolog Apidra Thiazolidinediones (TZDs) pioglitazone Actos Alternative Drugs (Weight neutral or may promote weightloss) These combinations tend to have fewer side-effects and less weight gain: Sulfonylureas glypizide glyburide glimepride chlorpropamide tolubutamide Glucotrol Diabeta Micronase Glynase Amaryl Diabinese metformin/pioglitazone (Actoplus Met) glipizide/metformin (Metaglip) glyburide/metformin (Glucovance) glimepiride/metformin

51 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 Feb; 100(2):342-62

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53 Antipsychotic and Anticonvulsant Medications and Weight Gain MEDICATIONS WEIGHTGAIN ASSOCIATED WITH USE ALTERNATIVES (WEIGHT REDUCTING IN PARENTHESES)* Antipsychotics Clozapine Risperidone Olanzapine Quetiapine Haloperidol Perphenazine Quetiapine Ziprasidone Aripiprizole Anticonvulsants Carbamazepine Gabapentin Valproate Lamotrigine? (Topiramate) (Zonisamide) * Only phentermine/topiramate ER is FDA-approved for chronic weight management in patients with BMI 30+ kg/m 2 or BMI kg/m 2 with one or more comorbidities J Clin Endocrinol Metab Feb; 100(2):342-62

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55 Antidepressant Medications and Weight Gain MEDICATIONS WEIGHTGAIN ASSOCIATED WITH USE ALTERNATIVES (WEIGHT REDUCTING IN PARENTHESES)* Antidepressants/mood stabilizers: tricyclic antidepressants Lithium Antidepressants/mood stabilizers: SSRIs Antidepressants/mood stabilizers: MAOI Amytriptyline Doxepin Imipramine Nortriptyline Trimipramine Mirtazapine Lithium Fluoxetine? Sertraline? Paroxetine Fluvoxamine Phenylzine Tranylcypromine (Bupropion) Nefazodone Fluoxetine (short term) Sertraline (< 1 yr) * Only naltrexone SR/ bupropion SR combination is FDA-approved for chronic weight management in patients with BMI 30+ kg/m 2 or BMI 27 <30 kg/m 2 with one or more comorbidities 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 J Clin Endocrinol Metab Feb; 100(2):342-62

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57 Antidepressant Medications and Weight Gain MEDICATIONS WEIGHTGAIN ASSOCIATED WITH USE ALTERNATIVES (WEIGHT REDUCTING IN PARENTHESES)* Antidepressants/mood stabilizers: tricyclic antidepressants Lithium Antidepressants/mood stabilizers: SSRIs Antidepressants/mood stabilizers: MAOI Amytriptyline Doxepin Imipramine Nortriptyline Trimipramine Mirtazapine Lithium Fluoxetine? Sertraline? Paroxetine Fluvoxamine Phenylzine Tranylcypromine (Bupropion) Nefazodone Fluoxetine (short term) Sertraline (< 1 yr) * Only naltrexone SR/ bupropion SR combination is FDA-approved for chronic weight management in patients with BMI 30+ kg/m 2 or BMI 27 <30 kg/m 2 with one or more comorbidities 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 J Clin Endocrinol Metab Feb; 100(2):342-62

58 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)

59 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

60 A Brighter Future For Patients

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