Applied Evidence

Obesity: When to consider medication

J Fam Pract. 2017 October;66(10):608-616

From The Journal of Family Practice | 2017;66(10):608-616.

References

1. Wing RR, Lang W, Wadden TA, et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care. 2011;34:1481-1486.

2. Magkos F, Fraterrigo G, Yoshino J. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab. 2016;23:591-601.

3. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2014;63(25 Pt B):2985-3023.

4. Sumithran P, Predergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365:1597-1604.

5. Greenway FL. Physiological adaptations to weight loss and factors favouring weight regain. Int J Obes (Lond). 2015;39:1188-1196.

6. Fothergill E, Guo J, Howard L, et al. Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity (Silver Spring). 2016;24:1612-1619.

7. Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015;100:342-362.

8. Saunders KH, Shukla AP, Igel LI, et al. Pharmacotherapy for obesity. Endocrinol Metab Clin North Am. 2016;45:521-538.

9. Saunders KH, Kumar RB, Igel LI, et al. Pharmacologic approaches to weight management: recent gains and shortfalls in combating obesity. Curr Atheroscler Rep. 2016;18:36.

10. US Food and Drug Administration. Drug approval package. Qsymia. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/022580Orig1s000_qsymia_toc.cfm. Accessed August 28, 2017.

11. Arena Pharmaceuticals. Arena Pharmaceuticals and Eisai announce FDA approval of BELVIQ® (lorcaserin HCl) for chronic weight management in adults who are overweight with a comorbidity or obese. Available at: http://invest.arenapharm.com/releasedetail.cfm?ReleaseID=687182. Accessed August 28, 2017.

12. Drugs.com. Contrave approval history. Available at: https://www.drugs.com/history/contrave.html. Accessed August 28, 2017.

13. US Food and Drug Administration. Drugs@FDA: FDA approved drug products. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=206321. Accessed August 28, 2017.

14. Igel LI, Kumar RB, Saunders KH, et al. Practical use of pharmacotherapy for obesity. Gastroenterology. 2017;152:1765-1779.

15. Adipex-P package insert. Available at: http://www.iodine.com/drug/phentermine/fda-package-insert. Accessed August 28, 2017.

16. Ionamin package insert. Available at: http://druginserts.com/lib/rx/meds/ionamin/. Accessed August 28, 2017.

17. Lomaira package insert. Available at: https://www.lomaira.com/Prescribing_Information.pdf. Accessed August 28, 2017.

18. Suprenza package insert. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202088s001lbl.pdf. Accessed August 28, 2017.

19. Aronne LJ, Wadden TA, Peterson C, et al. Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults. Obesity (Silver Spring). 2013;21:2163-2171.

20. Alli package labeling. Available at: http://druginserts.com/lib/otc/meds/alli-1/. Accessed August 28, 2017.

21. Xenical package insert. Available at: https://www.gene.com/download/pdf/xenical_prescribing.pdf. Accessed August 28, 2017.

22. Torgerson JS, Hauptman J, Boldrin MN, et al. 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. 2004;27:155-161.

23. Qsymia package insert. Available at: https://www.qsymia.com/pdf/prescribing-information.pdf. Accessed August 28, 2017.

24. Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2012;20:330-342.

25. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomized, placebo-controlled, phase 3 trial. Lancet. 2011;377:1341-1352.

26. Garvey WT, Ryan DH, Look M, et al. 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. 2012;95:297-308.

27. Belviq package insert. Available at: https://www.belviq.com/-/media/Files/BelviqConsolidation/PDF/Belviq_Prescribing_information-pdf.PDF?la=en. Accessed August 28, 2017.

28. Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363:245-256.

29. Fidler MC, Sanchez M, Raether B, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011;96:3067-3077.

30. O’Neil PM, Smith SR, Weissman NJ, et al. Randomized placebo controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity (Silver Spring). 2012;20:1426-1436.

31. Contrave package insert. Available at: https://contrave.com/wp-content/uploads/2017/05/Contrave_PI.pdf. Accessed August 28, 2017.

32. Greenway FL, Fujioka K, Plodkowski RA, et al. 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. 2010;376:595-605.

33. Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring). 2013;21:935-943.

34. Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring). 2011;19:110-120.

35. Hollander P, Gupta AK, Plodkowski R, et al. 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. 2013;36:4022-4029.

36. Saxenda package insert. Available at: http://www.novo-pi.com/saxenda.pdf. Accessed August 28, 2017.

37. Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373:11-22.

38. Davies MJ, Bergenstal R, Bode B, et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE Diabetes randomized clinical trial. JAMA. 2015;314:687-699.

39. Wadden TA, Hollander P, Klein S, et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013;37:1443-1451.

40. Saunders KH, Igel LI, Aronne LJ. An update on naltrexone/bupropion extended-release in the treatment of obesity. Expert Opin Pharmacother. 2016. [Epub ahead of print]

41. Thomas CE, Mauer EA, Shukla AP, et al. Low adoption of weight loss medications: a comparison of prescribing patterns of antiobesity pharmacotherapies and SGLT2s. Obesity (Silver Spring). 2016;24:1955-1961.

42. Qsymia Risk Evaluation and Mitigation Strategy (REMS). VIVUS, Inc. Available at: http://www.qsymiarems.com. Accessed January 16, 2017.

43. Zinman B, Wanner C, Lachin JM, et al. Empaglifozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128.

44. US Food and Drug Administration. FDA announces withdrawal fenfluramine and dexfenfluramine (Fen-Phen). Available at: https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm179871.htm. Accessed August 28, 2017.

45. Belviq XR package insert. Available at: https://www.belviq.com/-/media/Files/BelviqConsolidation/PDF/belviqxr_prescribing_information-pdf.PDF?la=en. Accessed January 16, 2017.

46. Smith SR, O’Neil PM, Astrup A. Early weight loss while on lorcaserin, diet and exercise as a predictor of week 52 weight-loss outcomes. Obesity (Silver Spring). 2014;22:2137-2146.

47. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-322.

48. Madsen LW, Knauf JA, Gotfredsen C, et al. GLP-1 receptor agonists and the thyroid: C-cell effects in mice are mediated via the GLP-1 receptor and not associated with RET activation. Endocrinology. 2012;153:1538-1547.

49. Fujioka K, O’Neil PM, Davies M, et al. Early weight loss with liraglutide 3.0 mg predicts 1-year weight loss and is associated with improvements in clinical markers. Obesity (Silver Spring). 2016;24:2278-2288.

CASE 4 William P, a 65-year-old man with obesity (BMI 39 kg/m2) who underwent Roux-en-Y gastric bypass surgery and who has type 2 diabetes, congestive heart failure, coronary artery disease, hypertension, and hyperlipidemia, remains concerned about his weight. He lost 100 lbs following surgery and maintained his weight for 3 years, but then regained 30 lbs. He comes in for an office visit because he’s concerned about his increasing blood sugar and wants to prevent further weight gain. His medications include metformin 1000 mg bid, lisinopril 5 mg/d, carvedilol 12.5 mg bid, simvastatin 20 mg/d, and aspirin 81 mg/d. Laboratory test results are normal except for a hemoglobin A1c of 8%. He denies pancreatitis and a personal or family history of thyroid cancer.

Which medication is an appropriate next step for Mr. P?

Discussion

Pharmacotherapy is a great option for this patient, who is regaining weight following bariatric surgery. Phentermine/topiramate ER is the only medication that would be contraindicated because of his heart disease. Lorcaserin and naltrexone SR/bupropion SR could be considered, but liraglutide 3 mg is the most appropriate option, given his need for further glucose control.

Medication is a great option for patients who are regaining weight after bariatric surgery.

Furthermore, the recent LEADER (Liraglutide effect and action in diabetes: evaluation of CV outcome results) trial reported a significant mortality benefit with liraglutide 1.8 mg/d among patients with type 2 diabetes and high CV risk.⁴⁷ The study found that liraglutide was superior to placebo in reducing CV events.

Contraindications. Ask patients about a history of pancreatitis before starting liraglutide 3 mg given the possible increased risk. In addition, liraglutide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2. Thyroid C-cell tumors have been found in rodents given supratherapeutic doses of liraglutide;⁴⁸ however, there is no evidence of liraglutide causing C-cell tumors in humans.

For patients taking a medication that can cause hypoglycemia, such as insulin or a sulfonylurea, monitor blood sugar and consider reducing the dose of that medication when starting liraglutide.

Administration and titration. Liraglutide is injected subcutaneously once daily. The dose is titrated up weekly to reduce gastrointestinal symptoms.³⁶ The most common adverse effects reported in phase III trials were nausea, diarrhea, and constipation.^37-39 Discontinue liraglutide 3 mg if the patient does not lose at least 4% of baseline body weight after 16 weeks.⁴⁹

CORRESPONDENCE
Katherine H. Saunders, MD, DABOM, Comprehensive Weight Control Center, Division of Endocrinology, Diabetes and Metabolism, Weill Cornell Medicine, 1165 York Avenue, New York, NY 10065; kph2001@med.cornell.edu.

References

4. Sumithran P, Predergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365:1597-1604.

5. Greenway FL. Physiological adaptations to weight loss and factors favouring weight regain. Int J Obes (Lond). 2015;39:1188-1196.

6. Fothergill E, Guo J, Howard L, et al. Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity (Silver Spring). 2016;24:1612-1619.

7. Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015;100:342-362.

8. Saunders KH, Shukla AP, Igel LI, et al. Pharmacotherapy for obesity. Endocrinol Metab Clin North Am. 2016;45:521-538.

9. Saunders KH, Kumar RB, Igel LI, et al. Pharmacologic approaches to weight management: recent gains and shortfalls in combating obesity. Curr Atheroscler Rep. 2016;18:36.

10. US Food and Drug Administration. Drug approval package. Qsymia. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/022580Orig1s000_qsymia_toc.cfm. Accessed August 28, 2017.

12. Drugs.com. Contrave approval history. Available at: https://www.drugs.com/history/contrave.html. Accessed August 28, 2017.

14. Igel LI, Kumar RB, Saunders KH, et al. Practical use of pharmacotherapy for obesity. Gastroenterology. 2017;152:1765-1779.

15. Adipex-P package insert. Available at: http://www.iodine.com/drug/phentermine/fda-package-insert. Accessed August 28, 2017.

16. Ionamin package insert. Available at: http://druginserts.com/lib/rx/meds/ionamin/. Accessed August 28, 2017.

17. Lomaira package insert. Available at: https://www.lomaira.com/Prescribing_Information.pdf. Accessed August 28, 2017.

18. Suprenza package insert. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202088s001lbl.pdf. Accessed August 28, 2017.

19. Aronne LJ, Wadden TA, Peterson C, et al. Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults. Obesity (Silver Spring). 2013;21:2163-2171.

20. Alli package labeling. Available at: http://druginserts.com/lib/otc/meds/alli-1/. Accessed August 28, 2017.

21. Xenical package insert. Available at: https://www.gene.com/download/pdf/xenical_prescribing.pdf. Accessed August 28, 2017.

23. Qsymia package insert. Available at: https://www.qsymia.com/pdf/prescribing-information.pdf. Accessed August 28, 2017.

24. Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2012;20:330-342.

27. Belviq package insert. Available at: https://www.belviq.com/-/media/Files/BelviqConsolidation/PDF/Belviq_Prescribing_information-pdf.PDF?la=en. Accessed August 28, 2017.

28. Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363:245-256.

29. Fidler MC, Sanchez M, Raether B, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011;96:3067-3077.

31. Contrave package insert. Available at: https://contrave.com/wp-content/uploads/2017/05/Contrave_PI.pdf. Accessed August 28, 2017.

33. Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring). 2013;21:935-943.

36. Saxenda package insert. Available at: http://www.novo-pi.com/saxenda.pdf. Accessed August 28, 2017.

37. Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373:11-22.

38. Davies MJ, Bergenstal R, Bode B, et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE Diabetes randomized clinical trial. JAMA. 2015;314:687-699.

40. Saunders KH, Igel LI, Aronne LJ. An update on naltrexone/bupropion extended-release in the treatment of obesity. Expert Opin Pharmacother. 2016. [Epub ahead of print]

42. Qsymia Risk Evaluation and Mitigation Strategy (REMS). VIVUS, Inc. Available at: http://www.qsymiarems.com. Accessed January 16, 2017.

43. Zinman B, Wanner C, Lachin JM, et al. Empaglifozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128.

45. Belviq XR package insert. Available at: https://www.belviq.com/-/media/Files/BelviqConsolidation/PDF/belviqxr_prescribing_information-pdf.PDF?la=en. Accessed January 16, 2017.

46. Smith SR, O’Neil PM, Astrup A. Early weight loss while on lorcaserin, diet and exercise as a predictor of week 52 weight-loss outcomes. Obesity (Silver Spring). 2014;22:2137-2146.

47. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-322.

Obesity: When to consider medication

References

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Is obesity a disease?