Updates on obesity pharmacotherapy
Amanda Velazquez
Bariatric Medicine and Internal Medicine, Kaiser Permanente Medical Center, Los Angeles, California
Search for more papers by this authorCorresponding Author
Caroline M. Apovian
Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts
Address for correspondence: Caroline M. Apovian, M.D., Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston Medical Center, Boston University School of Medicine, 88 East Newton Street, Robinson 4400, Boston, MA 02118. [email protected]Search for more papers by this authorAmanda Velazquez
Bariatric Medicine and Internal Medicine, Kaiser Permanente Medical Center, Los Angeles, California
Search for more papers by this authorCorresponding Author
Caroline M. Apovian
Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts
Address for correspondence: Caroline M. Apovian, M.D., Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston Medical Center, Boston University School of Medicine, 88 East Newton Street, Robinson 4400, Boston, MA 02118. [email protected]Search for more papers by this authorAbstract
Obesity is a chronic, relapsing disease that necessitates a multidisciplinary approach to management. Behavioral changes are the foundation to management, but adjunctive therapy is often warranted, including pharmacologic therapies and/or bariatric surgery. Until recently, treatment options included only short-term therapy (≤12 weeks), and paths beyond that schedule were challenging, as knowledge of the biology of obesity was lacking. With increased recognition of obesity as a chronic, complex medical disease, newer agents have been approved as long-term therapy, and the cornerstone of treatment is chronic behavior and lifestyle change. In the last decade, the Food and Drug Administration (FDA) has approved several new weight loss medications for the chronic management of obesity. In this review paper, we provide the latest updates on obesity pharmacotherapy. The main areas we will cover include (1) pharmacological management of obesity, (2) a review of FDA-approved weight loss medications, (3) comanagement of obesity and its metabolic sequelae (type 2 diabetes mellitus, hypertension, and dyslipidemia), and (4) obesity-centric prescribing for mental illness, neurological disorders, and contraceptive planning.
References
- 1 Understanding the American obesity epidemic. 2016. Accessed May 28, 2017. http://www.heart.org/HEARTORG/HealthyLiving/WeightManagement/Obesity/Understanding-the-American-Obesity-Epidemic_UCM_461650_Article.jsp-.WSrenxRh1cw.
- 2 Obesity and overweight fact sheet. 2016. Accessed March 18, 2017. http://www.who.int/mediacentre/factsheets/fs311/en/.
- 3Hurt, R.T., C. Kulisek, L.A. Buchanan & S.A. McClave. 2010. The obesity epidemic: challenges, health initiatives, and implications for gastroenterologists. Gastroenterol. Hepatol. (N. Y.) 6: 780–792.
- 4 U.S. pharmaceutical weight loss market. Accessed May 28, 2017. https://symphonyhealth.com/product/pharmaceutical-audit-suite-phast/.
- 5Weintraub, M., P.R. Sundaresan, B. Schuster, et al. 1992. Long-term weight control study. II (weeks 34 to 104). An open-label study of continuous fenfluramine plus phentermine versus targeted intermittent medication as adjuncts to behavior modification, caloric restriction, and exercise. Clin. Pharmacol. Ther. 51: 595–601.
- 6 “Fen-Phen” update (fenlfuramine, phentermine, dexfenfluramine). Accessed May 28, 2017. https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm180082.htm.
- 7Apovian, C.M., L.J. Aronne, D.H. Bessesen, et al. 2015. Pharmacological management of obesity: an endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 100: 342–362.
- 8Thomas, C.E., E.A. Mauer, A.P. Shukla, et al. 2016. Low adoption of weight loss medications: a comparison of prescribing patterns of antiobesity pharmacotherapies and SGLT2s. Obesity (Silver Spring) 24: 1955–1961.
- 9Samaranayake, N.R., K.L. Ong, R.Y. Leung & B.M. Cheung. 2012. Management of obesity in the National Health and Nutrition Examination Survey (NHANES), 2007–2008. Ann. Epidemiol. 22: 349–353.
- 10Xia, Y., C.M. Kelton, J.J. Guo, et al. 2015. Treatment of obesity: pharmacotherapy trends in the United States from 1999 to 2010. Obesity (Silver Spring) 23: 1721–1728.
- 11Colbert, J.A. & S. Jangi. 2013. Training physicians to manage obesity—back to the drawing board. N. Engl. J. Med. 369: 1389–1391.
- 12McAlpine, D.D. & A.R. Wilson. 2007. Trends in obesity-related counseling in primary care: 1995–2004. Med. Care 45: 322–329.
- 13Frank, A. 1993. Futility and avoidance. Medical professionals in the treatment of obesity. JAMA 269: 2132–2133.
- 14Apovian, C.M., W.T. Garvey & D.H. Ryan. 2015. Challenging obesity: patient, provider, and expert perspectives on the roles of available and emerging nonsurgical therapies. Obesity (Silver Spring) 23: S1–S26.
- 15Santo, M.A., D. Riccioppo, D. Pajecki, et al. 2016. Weight regain after gastric bypass: influence of gut hormones. Obes. Surg. 26: 919–925.
- 16Bray, G.A. 2013. Why do we need drugs to treat the patient with obesity? Obesity (Silver Spring) 21: 893–899.
- 17Bray, G.A. & D.H. Ryan. 2014. Update on obesity pharmacotherapy. Ann. N.Y. Acad. Sci. 1311: 1–13.
- 18Yanovski, S.Z. & J.A. Yanovski. 2014. Long-term drug treatment for obesity: a systematic and clinical review. JAMA 311: 74–86.
- 19Hadler, A.J. 1968. Sustained-action phendimetrazine in obesity. J. Clin. Pharmacol. 8: 113–117.
- 20Runyan, J.W., Jr. 1962. Observations on the use of phendimetrazine, a new anorexigenic agent, in obese diabetics. Curr. Ther. Res. Clin. Exp. 4: 270–275.
- 21Hampp, C., E.M. Kang & V. Borders-Hemphill. 2013. Use of prescription antiobesity drugs in the United States. Pharmacotherapy 33: 1299–1307.
- 22Haddock, C.K., W.S. Poston, P.L. Dill, et al. 2002. Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials. Int. J. Obes. Relat. Metab. Disord. 26: 262–273.
- 23Apovian, C.M. & N.W. Istfan. 2016. Obesity: guidelines, best practices, new research. Endocrinol. Metab. Clin. North Am. 45: xvii–xviii.
- 24Rothman, R.B., M.H. Baumann, C.M. Dersch, et al. 2001. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39: 32–41.
- 25Gotthardt, J.D. & N.T. Bello. 2016. Can we win the war on obesity with pharmacotherapy? Expert Rev. Clin. Pharmacol. 13: 1–9.
- 26Magnani, J.W., E.M. Hylek & C.M. Apovian. 2013. Obesity begets atrial fibrillation: a contemporary summary. Circulation 128: 401–405.
- 27Apovian, C.M. & N. Gokce. 2012. Obesity and cardiovascular disease. Circulation 125: 1178–1182.
- 28Munro, J.F., A.C. MacCuish, E.M. Wilson & L.J. Duncan. 1968. Comparison of continuous and intermittent anorectic therapy in obesity. Br. Med. J. 1: 352–354.
- 29Aronne, L.J., T.A. Wadden, C. Peterson, et al. 2013. Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults. Obesity (Silver Spring) 21: 2163–2171.
- 30 Phentermine pharcodynamics/kinetics. 2017. Accessed June 1, 2017. https://www.uptodate.com/contents/phentermine-patient-drug-information?source=see_link.
- 31 Lomaira. 2017. Accessed March 29, 2017. https://lomaira.com/Prescribing_Information.pdf.
- 32 In Brief: Phentermine (Lomaira) for weight loss. Dec. 5, 2016. The Medical Letter. The Medical Letter, Inc., New Rochelle, NY.
- 33Torgerson, J.S., J. Hauptman, M.N. Boldrin & L. Sjostrom. 2004. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care 27: 155–161.
- 34Rucker, D., R. Padwal, S.K. Li, et al. 2007. Long-term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ 335: 1194–1199.
- 35Allison, D.B., K.M. Gadde, W.T. Garvey, et al. 2012. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring) 20: 330–342.
- 36Gadde, K.M., D.B. Allison, D.H. Ryan, et al. 2011. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet 377: 1341–1352.
- 37Garvey, W.T., D.H. Ryan, M. Look, et al. 2012. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am. J. Clin. Nutr. 95: 297–308.
- 38O'Neil, P.M., S.R. Smith, N.J. Weissman, et al. 2012. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity (Silver Spring) 20: 1426–1436.
- 39Fidler, M.C., M. Sanchez, B. Raether, et al. 2011. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J. Clin. Endocrinol. Metab. 96: 3067–3077.
- 40Smith, S.R., N.J. Weissman, C.M. Anderson, et al. 2010. Multicenter, placebo-controlled trial of lorcaserin for weight management. N. Engl. J. Med. 363: 245–256.
- 41Connolly, H.M., J.L. Crary, M.D. McGoon, et al. 1997. Valvular heart disease associated with fenfluramine–phentermine. N. Engl. J. Med. 337: 581–588.
- 42Weissman, N.J., M. Sanchez, G.G. Koch, et al. 2013. Echocardiographic assessment of cardiac valvular regurgitation with lorcaserin from analysis of 3 phase 3 clinical trials. Circ. Cardiovasc. Imaging 6: 560–567.
- 43Greenway, F.L., M.J. Whitehouse, M. Guttadauria, et al. 2009. Rational design of a combination medication for the treatment of obesity. Obesity (Silver Spring) 17: 30–39.
- 44Hollander, P., A.K. Gupta, R. Plodkowski, et al. 2013. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care 36: 4022–4029.
- 45Wadden, T.A., J.P. Foreyt, G.D. Foster, et al. 2011. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring) 19: 110–120.
- 46Apovian, C.M., L. Aronne, D. Rubino, et al. 2013. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring) 21: 935–943.
- 47Greenway, F.L., K. Fujioka, R.A. Plodkowski, et al. 2010. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 376: 595–605.
- 48Fujioka, K., J. Braverman-Panza. 2016. Answers to clinical questions in the primary care management of people with obesity: pharmacologic management. J. Fam. Pract. 65: S16–S23.
- 49Jeon, W.S. & C.Y. Park. 2014. Antiobesity pharmacotherapy for patients with type 2 diabetes: focus on long-term management. Endocrinol. Metab. (Seoul) 29: 410–417.
- 50van Can, J., B. Sloth, C.B. Jensen, et al. 2014. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int. J. Obes. (Lond.) 38: 784–793.
- 51Pi-Sunyer, X., A. Astrup, K. Fujioka, et al. 2015. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N. Engl. J. Med. 373: 11–22.
- 52Davies, M.J., R. Bergenstal, B. Bode, et al. 2015. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE Diabetes Randomized Clinical Trial. JAMA 314: 687–699.
- 53Wadden, T.A., P. Hollander, S. Klein, et al. 2013. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance Randomized Study. Int. J. Obes. (Lond.) 37: 1443–1451.
- 54Marso, S.P., G.H. Daniels, K. Brown-Frandsen, et al. 2016. Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 375: 311–322.
- 55Eckel, R.H., S.M. Grundy & P.Z. Zimmet. 2005. The metabolic syndrome. Lancet 365: 1415–1428.
- 56Bray, G.A. 2004. Medical consequences of obesity. J. Clin. Endocrinol. Metab. 89: 2583–2589.
- 57Pappachan, J.M. & A.K. Viswanath. 2017. Medical management of diabesity: do we have realistic targets? Curr. Diab. Rep. 17: 4.
- 58Domecq, J.P., G. Prutsky, A. Leppin, et al. 2015. Clinical review: drugs commonly associated with weight change: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 100: 363–370.
- 59Salsali, A., G. Kim, H.J. Woerle, et al. 2016. Cardiovascular safety of empagliflozin in patients with type 2 diabetes: a meta-analysis of data from randomized placebo-controlled trials. Diabetes Obes. Metab. 18: 1034–1040.
- 60Lundby-Christensen, L., L. Tarnow, T.W. Boesgaard, et al. 2016. Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus-the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial. BMJ Open 6: e008376.
- 61James, P.A., S. Oparil, B.L. Carter, et al. 2014. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 311: 507–520.
- 62Sharma, A.M., T. Pischon, S. Hardt, et al. 2001. Hypothesis: beta-adrenergic receptor blockers and weight gain: a systematic analysis. Hypertension 37: 250–254.
- 63Correll, C.U., L. Maayan, J. Kane, et al. 2016. Efficacy for psychopathology and body weight and safety of topiramate-antipsychotic cotreatment in patients with schizophrenia spectrum disorders: results from a meta-analysis of randomized controlled trials. J. Clin. Psychiatry 77: e746–e756.
- 64Lotke, P.S., B. Kaneshiro. 2015. Safety and efficacy of contraceptive methods for obese and overweight women. Obstet. Gynecol. Clin. North Am. 42: 647–657.
- 65Sturm, R. & A. Hattori. 2013. Morbid obesity rates continue to rise rapidly in the United States. Int. J. Obes. (Lond.) 37: 889–891.
- 66 ASGE Bariatric Endoscopy Task Force and ASGE Technology Committee; Abu Dayyeh, B.K., N. Kumar, S.A. Edmundowicz, et al. 2015. ASGE Bariatric Endoscopy Task Force systematic review and meta-analysis assessing the ASGE PIVI thresholds for adopting endoscopic bariatric therapies. Gastrointest. Endosc. 82: 425–438.e5
- 67Shikora, S.A., J. Toouli, M.F. Herrera, et al. 2016. Intermittent vagal nerve block for improvements in obesity, cardiovascular risk factors, and glycemic control in patients with type 2 diabetes mellitus: 2-year results of the VBLOC DM2 study. Obes. Surg. 26: 1021–1028.
- 68 Geleis. 2014. Accessed October 4, 2017. http://www.gelesis.com/press-releases/06232014.php.