Medications That Can Cause Weight Gain

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Medications that Can Cause Weight GainDerrick Cetin, D.O.Obesity MedicineClinical Assistant Professor Dept. of MedicineCleveland Clinic Lerner College of Medicine of CaseWestern Reserve UniversityBariatric and Metabolic InstituteDigestive Disease Institute9/15/18

Drug-Induced Weight Gain, Audience Should Know: A possible serious side effect of many commonly used drugs used for avariety of disease states Leads to exacerbation of co-morbid conditions related to obesity due toassociated weight gain While some medications are more common than others to cause weightgain, not all individuals gain weight from every drug that has weight gainlisted as a side effect In many cases if possible, substitute an alternative medication to treatthe same condition that is weight neutral or weight negative

Case Study55 year old Caucasian female referred by bariatric surgeon for medical evaluationof weight regain.S/P RYGB 2003 with 125 lbs weight loss. Regained her weight and now at highestpost 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, mineralsupplementation and dietary recommendations. She has not been able to exerciseregularly due to a back injury.T2DM, HTN, and major depressive disorder.

Approach to Post Operative Bariatric Surgery Weight RegainPost Operative osocial

Approach to Post Operative Bariatric Surgery Weight RegainPost Operative osocial

Physiological Causes of Weight Gain PregnancyMenopauseSmoking cessationEndocrine diseaseHypothyroidismCushing's diseaseAdaptations: hypoleptinemia, energy efficiency, gut hormones (PYY)Weight-gain promoting medications

Physiological Causes of Weight Gain PregnancyMenopauseSmoking cessationEndocrine diseaseHypothyroidismCushing's diseaseAdaptations: hypoleptinemia, energy efficiency, gut hormones (PYY)Weight-gain promoting medications

Classification of Drugs That May Lead to Weight GainCNS drugsEndocrine agentsMiscellaneousAtypical antipsychoticsGlucocorticoidsBeta Blockerseg. prednisoneeg. metoprololeg. olanzapineAnti-epileptics (AEDs)eg. valproateLithiumHormonal contraceptiveseg. medroxyprogesteroneDiabetes agents:Anti-histamineseg. diphenhydramineSleep aidseg. zolpidemAntidepressants:Ø InsulinHIV medicationsØ Selective Serotonin reuptakeinhibitors (SSRIs)Ø SulfonylureasChemotherapieseg. glyburideeg. paroxiteneØ Tricyclic agentseg. nortriptylineØ Otherseg. venlafaxine, mirtazapineLeslie, et al. QJM. 2007; 100: 395-404Ø Thiazolidenedioneseg. pioglitazoneCommon Migraine Medications(prophylaxis)Gynecological medications

Antipsychotics and Weight GainMay substantially increase bodyweight:May somewhat increase bodyweight:Variable/neutral effects on bodyweight: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)Serdolect (Sertindole)LithiumObesity Algorithm . 2015-2016 Obesity Medicine Association.

Significant Weight Gain (³7%) with Antipsychotic ence (%)30Abilify [package insert], Geodon [package insert]. Risperdal [package insert]., Seroquel [package insert]., Zyprexa [package insert]Courtesy of Dr. Caroline Apovian

Mechanism(s) of Antipsychotic-Associated Weight Gain Review of the literature indicates that a group of factors are associatedwith weight gain rather than a single mechanism Coupled with genetic profile, the risk for antipsychotic-induced weightgain is heterogeneous among individuals and specific agents Targets for weight gain include receptor interactions involving serotonin,histamine, dopamine, adrenergic, cannabinoid, and muscarinic receptorsCNS Drugs. 2011 Dec 1; 25 (12): 1035-59

Relative Likelihood of Metabolic Disturbances with Atypical Antipsychotic MedicationsMedicationWeight GainGlucose MetabolismAbnormalitiesDyslipidemiaMetabolic SyndromeAmisulprideLowLowLow elperone OlanzapineHighHIghHighHighPaliperidone ResperidoneMediumMedium-to-lowLowMediumSulpiride QuetiapineMediumMedium-to-lowHighHighSertindoleLow ZiprasidoneLowLowLowLowZotepineMedium Primary Care Diabetes. 2009; 3: 5-15. Current Diabetes Reports. 2010; 10: 209-216.

Atypical Antipsychotic Medications are associated with weight gainPotential Mechanism 5 HT2c blockade H1 affinity

Clinical Practice Guidelines for the Use of Atypical AntipsychoticMedications Body weight at 4 week intervals and the quarterlyFasting plasma glucose at baseline, 12 weeks, and annuallyLipid profile at baseline, 12 weeks, and every 5 yearsWaist circumference at baseline and annuallyClinical 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 understoodand controversial It is likely that the weight change may have some underlying geneticunderpinningMeasurements of body weight before initiation of valproic acid therapyshould be done as part of the monitoring of patients with epilepsy to detectchanges before there are serious adverse consequences; an increase of 2kg of body weight after 1 month of treatment should imply considerations tochange antiepileptic drug therapy.Obes Rev. 2011 May; 12(5): e 32-43

Antidepressant Medications and Weight GainWEIGHT GAIN ASSOCIATE WITH USEAntidepressants/mood stabilizers:tricyclic iptylineMirtazapineAntidepressants/mood stabilizers: Bipolar disorderLithiumAntidepressants/mood stabilizers: SSRIsFluoxetine?Sertaline ?ParoxetineFluvoxamineSSRI use year or more cause weight gain of about 5 lbsSNRIs cause less long term weight gainAntidepressants/mood stabilizers: MAO InhibitorsJ Clin Endocrinol Metab. 2015 Feb; 100(2):342-62PhenylzineTranylcypromine

Why Weight Gain Happens with Antidepressants? Antidepressants work by interacting with muscarinic, acetylcholine, andthe histamine receptors; when blocked have a proclivity toward weightgain Tricyclic antidepressants block all these receptors, therefore reliablycause 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 associatedwith significant weight gain

Diabetes Medications Associated with Weight GainDrug Class/Type(and Potential Related Weight Gain)Common NameBrand NameInsulin (weight gain differs with typeand regimen used)Insulin lisproInsulin aspartInsulin glulisineHumalogNovologApidraThiazolidinediones (TZDs)pioglitazoneActosSulfonylureas binese

Diabetes Medications Associated with Weight GainDrug Class/Type(and Potential Related Weight Gain)Common NameBrand NameInsulin (weight gain differs with typeand regimen used)Insulin lisproInsulin aspartInsulin glulisineHumalogNovologApidraThiazolidinediones (TZDs)pioglitazoneActosSulfonylureas bineseShift in fat distribution from visceral tosubcutaneous adipose depots that is associatedwith improvements in hepatic and peripheraltissue sensitivity to insulin

Diabetes Medications Associated with Weight GainDrug Class/Type(and Potential Related Weight Gain)Common NameBrand NameInsulin (weight gain differs with typeand regimen used)Insulin lisproInsulin aspartInsulin glulisineHumalogNovologApidraThiazolidinediones (TZDs)pioglitazoneActosSulfonylureas bineseDrugs exert their hypoglycemic effects bystimulating insulin secretion from thepancreatic beta-cell

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 theurine, 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 ofhypoglycemia- promotes overeating to avoid hypoglycemia

Insulin-Associated Weight Gain in DiabetesDiabetes, 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 asa 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 expenditureReduction in the thermic effect of foodReduction in exercise toleranceIncrease in tirednessReduction in nonexercise thermogenesisInhibition of lipolysisExacerbation of insulin resistanceSharma 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- TrazadoneObesity Algorithm . 2015-2016 Obesity Medicine Association.

Human Immunodeficiency Virus (HIV) Medications and Weight Gain 33-75% of patients with HIV infection receiving highly active antiretroviraltherapy (HAART) develop a syndrome referred to as lipodystrophy All Protease inhibitors (PI) and the Nucleoside Reverse TranscriptaseInhibitors (NRITs), ddi, D4t, AZT linked to lipodystrophy, risk is greater thelonger the drug is used, and if older, Caucasian, or overweight/obeseObesity Algorithm . 2015-2016 Obesity Medicine Association

Lipodystrophy a Possible Side Effect of HIV Drugs Characteristic body habitus associated with peripheral wasting of fat inthe 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 inthe 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- CorticosteroidsObesity Algorithm . 2015-2016 Obesity Medicine Association.

Gynecologic Medications and Weight GainWEIGHT GAIN ASSOCIATED WITH USEMEDICATIONSALTERNATIVES(WEIGHT REDUCTING IN PARENTHESES)Oral contraceptivesProgestational steroidsHormonal contraceptives containingprogestational steroidsBarrier methodsIUDsEndometriosistreatmentDepot leuprolide acetateSurgical treatmentJ Clin Endocrinol Metab. 2015 Feb; 100(2):342-62

Cardiovascular Medications and Weight GainMEDICATIONSHypertensionmedicationsWEIGHT GAIN ASSOCIATED WITH USEα-blocker?β-blocker?J Clin Endocrinol Metab. 2015 Feb; 100(2):342-62ALTERNATIVES(WEIGHT REDUCTING IN PARENTHESES)ACE inhibitors?Calcium channel blockers ?Angiotensin-2 receptor antagonists

Antipsychotic and Anticonvulsant Medications and Weight GainMEDICATIONSWEIGHT GAIN ASSOCIATED WITH WEIGHT REDUCTING IN opiramate)(Zonisamide)* Only phentermine/topiramate ER is FDA-approved for chronic weight management in patientswith BMI 30 kg/m2 or BMI 27-29.9 kg/m2 with one or more comorbiditiesJ Clin Endocrinol Metab. 2015 Feb; 100(2):342-62

Metformin PreventsAntipsychotic Induced WeightGain in AdolescentsMetformin 850 bid,inaddition to program of dietand physical activity,prevented weight gain inadolescents gaining weight onantipsychotic agentsKlein DJ, et al Am J Psychiatry 2006; 163:2072–2079.

Diabetes Medications Associated with Weight Gain and AlternativesDrug Class/Type(and Potential RelatedWeight Gain)Common NameBrand NameInsulinInsulin lisproInsulin aspartInsulin glulisineHumalogNovologApidraThiazolidinediones iabetaMicronaseGlynaseAmarylDiabineseAlternative Drugs(Weight neutral or may promote weightloss)

Diabetes Medications Associated with Weight Gain and AlternativesDrug Class/Type(and Potential RelatedWeight Gain)Common NameBrand NameInsulinInsulin lisproInsulin aspartInsulin glulisineHumalogNovologApidraThiazolidinediones iabetaMicronaseGlynaseAmarylDiabineseThese drugs exert theirhypoglycemic effects by stimulatinginsulin secretion from thepancreatic beta-cell.Alternative Drugs(Weight neutral or may promote weightloss)

Diabetes Medications Associated with Weight Gain and AlternativesDrug Class/Type(and Potential RelatedWeight Gain)Common NameBrand NameInsulinInsulin lisproInsulin aspartInsulin glulisineHumalogNovologApidraThiazolidinediones ylAlternative Drugs(Weight neutral or may promote weightloss)

Diabetes Medications Associated with Weight Gain and AlternativesDrug Class/Type(and Potential RelatedWeight Gain)Common NameBrand NameAlternative Drugs(Weight neutral or may promote weightloss)InsulinInsulin lisproInsulin aspartInsulin glulisineHumalogNovologApidrametformin (Glucophage, Fortamet,Glumetza, Riomet)Thiazolidinediones yl

Diabetes Medications Associated with Weight Gain and AlternativesDrug Class/Type(and Potential RelatedWeight Gain)Common NameBrand NameAlternative Drugs(Weight neutral or may promote weightloss)InsulinInsulin lisproInsulin aspartInsulin glulisineHumalogNovologApidrametformin (Glucophage, Fortamet,Glumetza, Riomet)SGLT 2 inhibitorsThiazolidinediones yl

Diabetes Medications Associated with Weight Gain and AlternativesDrug Class/Type(and Potential RelatedWeight Gain)Common NameBrand NameAlternative Drugs(Weight neutral or may promote weightloss)InsulinInsulin lisproInsulin aspartInsulin glulisineHumalogNovologApidraThiazolidinediones (TZDs)pioglitazoneActosmetformin (Glucophage, Fortamet,Glumetza, Riomet)SGLT 2 inhibitorslinagliptin (Tradjenta)saxagliptin (Onglyza)sitagliptin (Januvia)SulfonylureasglimeprideAmaryl

Diabetes Medications Associated with Weight Gain and AlternativesDrug Class/Type(and Potential RelatedWeight Gain)Common NameBrand NameAlternative Drugs(Weight neutral or may promote weightloss)InsulinInsulin lisproInsulin aspartInsulin glulisineHumalogNovologApidraThiazolidinediones (TZDs)pioglitazoneActosmetformin (Glucophage, Fortamet,Glumetza, Riomet)SGLT 2 inhibitorslinagliptin (Tradjenta)saxagliptin (Onglyza)sitagliptin (Januvia)exenatide (Byetta)liraglutide (Victoza)SulfonylureasglimeprideAmaryl

Diabetes Medications Associated with Weight Gain and AlternativesDrug Class/Type(and Potential RelatedWeight Gain)Common NameBrand NameAlternative Drugs(Weight neutral or may promote weightloss)InsulinInsulin lisproInsulin aspartInsulin glulisineHumalogNovologApidraThiazolidinediones (TZDs)pioglitazoneActosmetformin (Glucophage, Fortamet,Glumetza, Riomet)SGLT 2 inhibitorslinagliptin (Tradjenta)saxagliptin (Onglyza)sitagliptin (Januvia)exenatide (Byetta)liraglutide (Victoza)acarbose (Precose, Prandase)SulfonylureasglimeprideAmaryl

Diabetes Medications Associated with Weight Gain and AlternativesDrug Class/Type(and Potential RelatedWeight Gain)Common NameBrand NameAlternative Drugs(Weight neutral or may promote weightloss)InsulinInsulin lisproInsulin aspartInsulin glulisineHumalogNovologApidraThiazolidinediones (TZDs)pioglitazoneActosmetformin (Glucophage, Fortamet,Glumetza, Riomet)SGLT 2 inhibitorslinagliptin (Tradjenta)saxagliptin (Onglyza)sitagliptin (Januvia)exenatide (Byetta)liraglutide (Victoza)acarbose (Precose, Prandase)miglitol (Glyset)SulfonylureasglimeprideAmaryl

Diabetes Medications Associated with Weight Gain and AlternativesDrug Class/Type(and Potential RelatedWeight Gain)Common NameBrand NameAlternative Drugs(Weight neutral or may promote weightloss)InsulinInsulin lisproInsulin aspartInsulin glulisineHumalogNovologApidraThiazolidinediones (TZDs)pioglitazoneActosmetformin (Glucophage, Fortamet,Glumetza, Riomet)SGLT 2 inhibitorslinagliptin (Tradjenta)saxagliptin (Onglyza)sitagliptin (Januvia)exenatide (Byetta)liraglutide (Victoza)acarbose (Precose, Prandase)miglitol (Glyset)Pramlintide (Amylin)SulfonylureasglimeprideAmaryl

Diabetes Medications Associated with Weight Gain and AlternativesDrug Class/Type(and Potential RelatedWeight Gain)Common NameBrand NameAlternative Drugs(Weight neutral or may promote weightloss)InsulinInsulin lisproInsulin aspartInsulin glulisineHumalogNovologApidraThiazolidinediones iabetaMicronaseGlynaseAmarylDiabinesemetformin (Glucophage, Fortamet,Glumetza, Riomet)SGLT 2 inhibitorslinagliptin (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

Diabetes Medications Associated with Weight Gain and AlternativesDrug Class/Type(and Potential RelatedWeight Gain)Common NameBrand NameInsulinInsulin lisproInsulin aspartInsulin glulisineHumalogNovologApidraThiazolidinediones (TZDs)pioglitazoneActosAlternative Drugs(Weight neutral or may promote weightloss)These combinations tend to have fewerside-effects and less weight naseAmarylDiabinesemetformin/pioglitazone (Actoplus Met)glipizide/metformin (Metaglip)glyburide/metformin (Glucovance)glimepiride/metformin

Drugs That Cause Weight Gain and Some Alternatives Patients with obesity and T2DM requiring insulin therapy, suggest adding at leastone of the following: metformin, pramlintide, or GLP-1 receptor agonists to mitigateassociated weight gain due to insulin The first-line insulin for this type of patient should be basal insulin (this is preferableto using either insulin alone or insulin with sulfonylurea) Recommend the initial insulin therapy strategy consider a preferential trial of basalinsulin prior to premixed insulins or combination insulin therapyJ Clin Endocrinol Metab. 2015 Feb; 100(2):342-62

Antipsychotic and Anticonvulsant Medications and Weight GainMEDICATIONSWEIGHT GAIN ASSOCIATED WITH WEIGHT REDUCTING IN opiramate)(Zonisamide)* Only phentermine/topiramate ER is FDA-approved for chronic weight management in patientswith BMI 30 kg/m2 or BMI 27-29.9 kg/m2 with one or more comorbiditiesJ Clin Endocrinol Metab. 2015 Feb; 100(2):342-62

Antidepressant Medications and Weight GainMEDICATIONSWEIGHT GAIN ASSOCIATED WITH USEAntidepressants/moodstabilizers: hiumAntidepressants/moodstabilizers: tidepressants/moodstabilizers: MAOIPhenylzineTranylcypromineALTERNATIVES(WEIGHT REDUCTING IN PARENTHESES)*(Bupropion)NefazodoneFluoxetine (short term)Sertraline ( 1 yr)* Only naltrexone SR/ bupropionSR combination is FDA-approvedfor chronic weight managementin patients with BMI 30 kg/m2 orBMI 27 30 kg/m2 with one ormore comorbiditiesBupropion is the only antidepressant associated with long-term weight loss, but only in nonsmokers, according to anew retrospective cohort study published in the Journal of Clinical Medicine, April 13, 2016J Clin Endocrinol Metab. 2015 Feb; 100(2):342-62

Antidepressant Medications and Weight GainMEDICATIONSWEIGHT GAIN ASSOCIATED WITH USEAntidepressants/moodstabilizers: hiumAntidepressants/moodstabilizers: tidepressants/moodstabilizers: MAOIPhenylzineTranylcypromineALTERNATIVES(WEIGHT REDUCTING IN PARENTHESES)*(Bupropion)NefazodoneFluoxetine (short term)Sertraline ( 1 yr)* Only naltrexone SR/ bupropion SRcombination is FDA-approved forchronic weight management inpatients with BMI 30 kg/m2 orBMI 27 30 kg/m2 with one ormore comorbiditiesBupropion is the only antidepressant associated with long-term weight loss, but only in nonsmokers, according to a newretrospective cohort study published in the Journal of Clinical Medicine, April 13, 2016J Clin Endocrinol Metab. 2015 Feb; 100(2):342-62

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 modifiableenvironmental & lifestyle factors to consider when evaluating a patient forweight gain Drug-induced weight gain is a serious side effect of many commonlyused medications leading to noncompliance with therapy andexacerbation of comorbid conditions related to obesity If possible discontinue or change weight gain-promoting medications toan alternative that has a weight neutral or a weight negative effect An exception, is if a medication is specifically indicated for an underlyingcondition, should be continued regardless of the effects on weight gain

A Brighter Future For Patientscetind@ccf.org

Thank youThank youContact: heinbel@ccf.org

- 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

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