Weight Loss Pharmacotherapy: Current and Future Therapies

Abstract

The rising prevalence of obesity is of major concern. There are currently 5 Food and Drug Administration-approved medications for the treatment of obesity: orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide 3.0 mg, and semaglutide 2.4 mg. Surgical options such as bariatric surgery and endoscopic surgery induce more durable weight loss than pharmacotherapy or lifestyle interventions alone. However, patients often experience weight regain and weight loss plateau after surgery. The addition of multimodal or multihormonal pharmacotherapy is a promising tool to address these challenges. The optimal timing of obesity pharmacotherapy with surgical and endoscopic interventions requires further investigation.

Keywords: Bariatric surgery; Endoscopic bariatric surgery; GLP-1 agonist; Obesity; Pharmacotherapy; Weight loss.

Figure 1.

Change in weight after laparoscopic sleeve gastrectomy (LSG) for those treated with phentermine and topiramate extended release (phen/top) + LSG versus LSG alone. From: Ard JD, Beavers DP, Hale E, Miller G, McNatt S, Fernandez A. Use of phentermine-topiramate extended release in combination with sleeve gastrectomy in patients with BMI 50 kg/m2 or more. Surg Obes Relat Dis. 2019;15(7):1039–1043. doi:10.1016/j.soard.2019.04.017

Figure 2.

Change in body weight among patients who received placebo versus naltrexone 16mg plus bupropion or naltrexone 32mg plus bupropion. From: 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 [published correction appears in Lancet. 2010 Aug 21;376(9741):594] [published correction appears in Lancet. 2010 Oct 23;376(9750):1392]. Lancet. 2010;376(9741):595–605. doi:10.1016/S0140-6736(10)60888-4

Figure 3.

Weight loss in liraglutide groups compared to placebo From: 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(1):11–22. doi:10.1056/NEJMoa1411892

Figure 4.

Efficacy of High-Dose Liraglutide as an Adjunct for Weight Loss in Patients with Prior Bariatric Surgery From: ye P, Modi R, Cawsey S, Sharma AM. Efficacy of High-Dose Liraglutide as an Adjunct for Weight Loss in Patients with Prior Bariatric Surgery. Obes Surg. 2018;28(11):3553–3558. doi:10.1007/s11695-018-3393-7

Figure 5.

Percentages of patients who reached weight loss of at least 5%, 10%, 15%, and 20%, respectively, following adjunct treatment with semaglutide once-weekly for 1, 3, and 6 months. FU, follow-up; N, number of individuals From: Lautenbach A, Wernecke M, Huber TB, et al. The Potential of Semaglutide Once-Weekly in Patients Without Type 2 Diabetes with Weight Regain or Insufficient Weight Loss After Bariatric Surgery-a Retrospective Analysis. Obes Surg. 2022;32(10):3280–3288. doi:10.1007/s11695-022-06211-9

Figure 6.

Heterogeneity in weight loss response after approximately 12 months with several therapeutic approaches currently available. From: Perdomo CM, Cohen RV, Sumithran P, Clément K, Frühbeck G. Contemporary medical, device, and surgical therapies for obesity in adults. Lancet. 2023;401(10382):1116–1130. doi:10.1016/S0140-6736(22)02403-5

Figure 7.

Gastric bypass patients’ post-surgery weight outcome trajectories and dietary management phases From: Lynch A. “When the honeymoon is over, the real work begins:” Gastric bypass patients’ weight loss trajectories and dietary change experiences. Soc Sci Med. 2016;151:241–249. doi:10.1016/j.socscimed.2015.12.024