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Research ArticleTools for Practice

Semaglutide for weight loss

Mo Ojeniran, Betty Dube, Allison Paige, Joey Ton and Adrienne J. Lindblad
Canadian Family Physician November 2021, 67 (11) 842; DOI: https://doi.org/10.46747/cfp.6711842
Mo Ojeniran
Student pharmacist in the Faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta in Edmonton.
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Betty Dube
Student pharmacist in the Faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta in Edmonton.
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Allison Paige
Medical Lead of Kildonan Medical Centre at Seven Oaks General Hospital in Winnipeg and Lecturer at the University of Manitoba.
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Joey Ton
Clinical Evidence Expert for the CFPC.
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Adrienne J. Lindblad
Clinical Evidence Expert for the CFPC.
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Clinical question

Is semaglutide (SGT) effective for weight loss?

Bottom line

Used with lifestyle changes, 2.4 mg of subcutaneous SGT weekly resulted in a mean 10% to 15% weight loss (10 to 15 kg) over 68 weeks versus 2% to 3% (3 to 4 kg) with placebo (PC). Most (70% to 80%) lost 5% or more of their body weight. About 75% had gastrointestinal side effects, but few discontinued treatment. Weight was regained on medication discontinuation.

Evidence

Differences were statistically significant unless noted.

  • In 4 RCTs, patients (baseline weight 96 to 105 kg) were treated for weight loss with 2.4 mg of subcutaneous SGT weekly and lifestyle interventions (counseling, diet, and physical activity).1-4

    • - An RCT of nondiabetic patients (N = 1961)1: After 68 weeks, mean weight loss was 15% (15 kg) versus 2% (3 kg) PC. The proportion of those who lost weight (≥ 5%) was 86% versus 32% (PC), with a number needed to treat (NNT) = 2, while the proportion who lost more weight (≥ 10%) was 69% versus 12% (PC), NNT = 2. Weight loss plateaued around week 60.

    • — Gastrointestinal adverse effects (AEs): 74% versus 48% (PC), number needed to harm (NNH) = 3. Withdrawals due to AEs were 7% versus 3% (PC), NNH = 25.

    • - Similar results in an RCT (N = 611) of SGT with intensive lifestyle interventions: 16% (17 kg) versus 6% (6 kg) PC.2

    • - Dose-finding RCT3 of diabetic patients (N = 1210) given either 2.4 mg of SGT weekly, 1.0 mg of SGT weekly, or PC: After 68 weeks, mean weight loss was 10% (2.4 mg), 7% (1.0 mg), and 3% (PC). Proportion who lost weight (≥ 5%) was 69% (2.4 mg) versus 57% (1.0 mg) versus 29% (PC). For 2.4 mg versus 1.0 mg, NNT = 9.

    • — The AEs were similar between doses.

    • - Weight-maintenance RCT (N = 803)4: Nondiabetic participants were given 2.4 mg of SGT weekly for 20 weeks and then randomized to either continued SGT or PC. After 48 weeks, the continued SGT group lost 8% body weight compared with a 7% weight gain in the PC group.

Context

  • Weight loss with oral SGT studied as a secondary outcome in cardiovascular disease and glucose-lowering trials found that weight loss was 4.6% (4.2 kg) versus 0.9% (0.8 kg) with PC at 15.9 months.5

  • In an SGT-sponsored RCT, high-dose SGT (0.4 mg/day) was superior to liraglutide (3 mg/day). Weight loss was 14% (17 kg) SGT versus 8% (8 kg) liraglutide. Weight loss was similar between 0.1 mg of SGT daily and liraglutide.6

  • Semaglutide (2.4 mg) is not available now in Canada, but lower doses are7 (1 mg/week costs about $ 200/month8).

Implementation

Besides weight loss, SGT increased quality of life for 40% to 50% of participants compared with about 30% taking PC.1 Semaglutide is usually started at 0.25 mg weekly and is increased by 0.25 mg every 4 weeks until the target dose is reached (as tolerated).9 Nausea and gastrointestinal upset are reported AEs, particularly during dose escalation.1,9 Adherence to weekly subcutaneous injections may be better than for daily injections.10 Other glucagon-like peptide 1 agonists and SGT should likely be avoided in patients with history of medullary thyroid carcinoma, pancreatitis, or tachyarrhythmias.9

Notes

Tools for Practice articles in Canadian Family Physician are adapted from peer-reviewed articles at www.toolsforpractice.ca and summarize practice-changing medical evidence for primary care. Coordinated by Dr G. Michael Allan and Dr Adrienne J. Lindblad, articles are developed by the Patients, Experience, Evidence, Research (PEER) team and supported by the College of Family Physicians of Canada and its Alberta, Ontario, and Saskatchewan Chapters. Feedback is welcome and can be sent to toolsforpractice{at}cfpc.ca.

Footnotes

  • Competing interests

    None declared

  • The opinions expressed in Tools for Practice articles are those of the authors and do not necessarily mirror the perspective and policy of the College of Family Physicians of Canada.

  • This article is eligible for Mainpro+ certified Self-Learning credits. To earn credits, go to www.cfp.ca and click on the Mainpro+ link.

  • La traduction en français de cet article se trouve à www.cfp.ca dans la table des matières du numéro de novembre 2021 à la page e296.

  • Copyright © 2021 the College of Family Physicians of Canada

References

  1. 1.↵
    1. Wilding JPH,
    2. Batterham RL,
    3. Calanna S,
    4. Davies M,
    5. Van Gaal LF,
    6. Lingvay I, et al.
    Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021;384(11):989.
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    1. Wadden TA,
    2. Bailey TS,
    3. Billings LK,
    4. Davies M,
    5. Frias JP,
    6. Koroleva A, et al.
    Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial. JAMA 2021;325(14):1403-13.
    OpenUrlPubMed
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    1. Davies M,
    2. Færch L,
    3. Jeppesen OK,
    4. Pakseresht A,
    5. Pedersen SD,
    6. Perreault L, et al.
    Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet 2021;397(10278):971-84.
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    1. Rubino D,
    2. Abrahamsson N,
    3. Davies M,
    4. Hesse D,
    5. Greenway FL,
    6. Jensen C, et al.
    Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA 2021;325(14):1414-25.
    OpenUrl
  5. 5.↵
    1. Husain M,
    2. Birkenfeld AL,
    3. Donsmark M,
    4. Dungan K,
    5. Eliaschewitz FG,
    6. Franco DR, et al.
    Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2019;381(9):841-51.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. O’Neil PM,
    2. Birkenfeld AL,
    3. McGowan B,
    4. Mosenzon O,
    5. Pedersen SD,
    6. Wharton S, et al.
    Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet 2018;392(10148):637-49.
    OpenUrl
  7. 7.↵
    1. Health Canada
    . Drug product database. Ottawa, ON: Government of Canada; 2015. Available from: https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database.html. Accessed 2021 Sep 30.
  8. 8.↵
    1. Falk J,
    2. Friesen K,
    3. Bugden S.
    Price comparison of commonly prescribed medications in Manitoba (2021). Winnipeg, MB: Meds Conference; 2021. Available from: https://medsconference.files.wordpress.com/2021/07/price-comparison-commonly-rx-drugs-mb-2020-july-26-2021.pdf. Accessed 2021 Sep 30.
  9. 9.↵
    Ozempic [product monograph]. Mississauga, ON: Novo Nordisk Canada; 2021. Available from: https://www.novonordisk.ca/content/dam/Canada/AFFILIATE/www-novonordisk-ca/OurProducts/PDF/ozempic-product-monograph.pdf. Accessed 2021 Sep 30.
  10. 10.↵
    1. Weeda ER,
    2. Muraoka AK,
    3. Brock MD,
    4. Cannon JM.
    Medication adherence to injectable glucagon-like peptide-1 (GLP-1) receptor agonists dosed once weekly vs once daily in patients with type 2 diabetes: a meta-analysis. Int J Clin Pract 2021;75(9):e14060.
    OpenUrl
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Canadian Family Physician: 67 (11)
Canadian Family Physician
Vol. 67, Issue 11
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Semaglutide for weight loss
Mo Ojeniran, Betty Dube, Allison Paige, Joey Ton, Adrienne J. Lindblad
Canadian Family Physician Nov 2021, 67 (11) 842; DOI: 10.46747/cfp.6711842

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Semaglutide for weight loss
Mo Ojeniran, Betty Dube, Allison Paige, Joey Ton, Adrienne J. Lindblad
Canadian Family Physician Nov 2021, 67 (11) 842; DOI: 10.46747/cfp.6711842
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