Pharmacotherapy for weight loss in adults with type 2 diabetes: a systematic review of randomised controlled trials

Claudia Coelho, Rachel Agius, James Crane, Barbara McGowan

Abstract


Background: Clinically significant weight loss improves glycaemic control and cardiovascular disease risk in patients with type 2 diabetes (T2DM).

Aim: To identify and assess the efficacy of medical treatments for weight loss in adults with T2DM.

Methods: A systematic review was conducted of peer- reviewed literature between July 2004 and July 2020 via PubMed, Embase, Web of Science, medRxiv and Cochrane Central Register of Controlled Trials. Randomised controlled trials (RCTs) in English investigating medical treatments for weight loss in patients with T2DM were included. RCTs of pharmacotherapy withdrawn from the market were excluded. No minimum length of follow-up time was established. Outcomes of interest were changes from baseline in body weight (%), changes from baseline in HbA1c (%, mmol/mol) and proportion of patients who achieved ≥5% weight loss. Quality assessment was evaluated using the Jadad score.

Results: Fifteen RCTs were included with a total of 4,207 participants with T2DM. Interventions included medications approved for obesity management (orlistat, liraglutide, naltrexone-bupropion and phentermine-topiramate) and other agents investigated for the primary purpose of weight loss (topiramate, metreleptin, dapagliflozin and exenatide) compared with placebo. The duration of the intervention varied from 12 to 56 weeks. Placebo-adjusted body weight loss ranged from 2.2% to 7.3%. Furthermore, 30.5–77.0% of patients achieved ≥5% weight loss. Placebo-adjusted change in glycated haemoglobin was 0.3–1.5% (3.3–16.4 mmol/mol).

Conclusion: Current evidence demonstrates that pharmacotherapy for weight loss, except for leptin, is associated with weight loss and glycaemic improvement in patients with T2DM.


Keywords


obesity, pharmacotherapy, type 2 diabetes, weight loss, systematic review

Full Text:

PDF HTML

References


Eckel RH, Kahn SE, Ferrannini E, et al. Obesity and type 2 diabetes: what can be unified and what needs to be individualized? J Clin Endocrinol Metab 2011;96(6):1654–63. https://doi.org/10.1210/jc.2011-0585

Cho NH, Shaw JE, Karuranga S, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 2018;138:271–81. https://doi.org/10.1016/j.diabres.2018.02.023

Anderson JW, Kendall CWC, Jenkins DJA. Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. J Am Coll Nutr 2003;22(5):331–9. https://doi.org/10.1080/07315724.2003.10719316

Leitner DR, Frühbeck G, Yumuk V, et al. Obesity and type 2 diabetes: two diseases with a need for combined treatment strategies - EASO can lead the way. Obes Facts 2017;10(5):483–92. https://doi.org/10.1159/000480525

Matyjaszek-Matuszek B, Szafraniec A, Porada D. Pharmacotherapy of obesity — state of the art. Endokrynol Pol 2018;69(4):448–66. https://doi.org/10.5603/ep.2018.0048

Benaiges D, Pedro-Botet J, Flores-Le Roux JA, et al. Past, present and future of pharmacotherapy for obesity. Clinica e Investigacion en Arteriosclerosis 2017;29(6):256–64. https://doi.org/10.1016/j.artere.2017.06.003

Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17(1):1–2. https://doi.org/10.1016/0197-2456(95)00134-4

Berne C. A randomized study of orlistat in combination with a weight management programme in obese patients with type 2 diabetes treated with metformin. Diabet Med 2005;22(5):612–18. https://doi.org/10.1111/j.1464-5491.2004.01474.x

Kuo CS, Pei D, Yao CY, et al. Effect of orlistat in overweight poorly controlled Chinese female type 2 diabetic patients: a randomised, double-blind, placebo-controlled study. Int J Clin Pract 2006;60(8):906–10. https://doi.org/10.1111/j.1742-1241.2006.01052.x

Derosa G, Cicero AFG, D’Angelo A, et al. Effects of 1-year orlistat treatment compared to placebo on insulin resistance parameters in patients with type 2 diabetes. J Clin Pharm Ther 2012;37(2):187–95. https://doi.org/10.1111/j.1365-2710.2011.01280.x

Guy-Grand B, Drouin P, Eschwège E, et al. Effects of orlistat on obesity-related diseases: a six-month randomized trial. Diabetes Obes Metab 2004;6(5):375–83. https://doi.org/10.1111/j.1462-8902.2004.00359.x

Shi YF, Pan CY, Hill J, et al. Orlistat in the treatment of overweight or obese Chinese patients with newly diagnosed type 2 diabetes. Diabet Med 2005;22(12):1737–43. https://doi.org/10.1111/j.1464-5491.2005.01723.x

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(7):687–99. https://doi.org/10.1001/jama.2015.9676

Garvey WT, Birkenfeld AL, Dicker D, et al. Efficacy and safety of liraglutide 3.0 mg in individuals with overweight or obesity and type 2 diabetes treated with basal insulin: the SCALE insulin randomized controlled trial. Diabetes Care 2020;43(5):1085–93. https://doi.org/10.2337/dc19-1745

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(12):4022–9. https://doi.org/10.2337/dc13-0234

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 randomised, placebo-controlled, phase 3 trial. Lancet 2011;377(9774): 1341–52. https://doi.org/10.1016/s0140-6736(11)60205-5

Apovian CM, Bergenstal RM, Cuddihy RM, et al. Effects of exenatide combined with lifestyle modification in patients with type 2 diabetes. Am J Med 2010;123(5):468.e9–17. https://doi.org/10.1016/j.amjmed.2009.11.019

Bolinder J, Ljunggren Ö, Kullberg J, et al. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 2012;97(3):1020–31. https://doi.org/10.1210/jc.2011-2260

Moon H-S, Matarese G, Brennan AM, et al. Efficacy of metreleptin in obese patients with type 2 diabetes: cellular and molecular pathways underlying leptin tolerance. Diabetes 2011;60(6):1647–56. https://doi.org/10.2337/db10-1791

Stenlöf K, Rössner S, Vercruysse F, et al. Topiramate in the treatment of obese subjects with drug-naive type 2 diabetes. Diabetes Obes Metab 2007;9(3):360–8. https://doi.org/10.1111/j.1463-1326.2006.00618.x

Toplak H, Hamann A, Moore R, et al. Efficacy and safety of topiramate in combination with metformin in the treatment of obese subjects with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Int J Obes 2007;31(1):138–46. https://doi.org/10.1038/sj.ijo.0803382

Rosenstock J, Hollander P, Gadde KM, et al. A randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of topiramate controlled release in the treatment of obese type 2 diabetic patients. Diabetes Care 2007;30(6):1480–6. https://doi.org/10.2337/dc06-2001

Goldstein DJ, Potvin JH, Hirsch J. Long-term weight loss: the effect of pharmacologic agents. Am J Clin Nutr 1994;60(5):647–57. https://doi.org/10.1093/ajcn/60.5.647

Norris SL, Zhang X, Avenell A, et al. Efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes mellitus: a meta-analysis. Arch Intern Med 2004;164(13):1395–404. https://doi.org/10.1001/archinte.164.13.1395

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(9741):595–605. https://doi.org/10.1016/s0140-6736(10)60888-4

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 2013;21:935–43. https://doi.org/10.1002/oby.20309

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. https://doi.org/10.1056/nejmoa1411892

Perri MG, Sears SF, Clark JE. Strategies for improving maintenance of weight loss: toward a continuous care model of obesity management. Diabetes Care 1993;16(1):200–09. https://doi.org/10.2337/diacare.16.1.200

DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med 1999;131(4):281–303. https://doi.org/10.7326/0003-4819-131-4-199908170-00008

Apovian CM, Okemah J, O’Neil PM. Body weight considerations in the management of type 2 diabetes. Advan Ther 2019;36(1):44–58. https://doi.org/10.1007/s12325-018-0824-8

Brown E, Wilding JPH, Barber TM, et al. Weight loss variability with SGLT2 inhibitors and GLP‐1 receptor agonists in type 2 diabetes mellitus and obesity: mechanistic possibilities. Obes Rev 2019;20:816–28. https://doi.org/10.1111/obr.12841

Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the treatment of obesity: key elements of the STEP Trials 1 to 5. Obesity 2020; 28:1050–61. https://doi.org/10.1002/oby.22794

Damci T, Yalin S, Balci H, et al. Orlistat augments postprandial increases in glucagon-like peptide 1 in obese type 2 diabetic patients. Diabetes Care 2004;27(5):1077–80. https://doi.org/10.2337/diacare.27.5.1077

Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375(4):311–22. https://doi.org/10.1056/nejmoa1603827

Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019;380(4):347–57. https://doi.org/10.1056/nejmc1902837

Nissen SE, Wolski KE, Prcela L, et al. Effect of naltrexone-bupropion on major adverse cardiovascular events in overweight and obese patients with cardiovascular risk factors: a randomized clinical trial. JAMA 2016; 315(10):990–1004. https://doi.org/10.1001/jama.2016.1558




DOI: https://doi.org/10.15277/bjd.2021.281

Refbacks

  • There are currently no refbacks.


The Journal of the Association of British Clinical Diabetologists