3 Weight Loss Injections for Sustainable Results
The global prevalence of obesity, a serious chronic disease, has reached alarming levels, with over 650 million adults living with obesity. Obesity is associated with an increased risk for over 200 other chronic diseases, including type 2 diabetes, heart disease, stroke, fatty liver disease, depression, sleep apnea, and some cancers.1 In the United States, about 42% of all adults live with obesity, and two-thirds of adults meet the criteria for overweight (>25 kg/m2) or obesity (>30 kg/m2).2,3
Because obesity is associated with significant morbidity and economic burden, there has been interest in developing medications to reduce the risk of cardiovascular and other chronic diseases related to obesity.4 As of 11/9/2023, there are now three FDA-approved medications for weight loss: Wegovy (semaglutide), Zepbound (tirzepatide), and Saxenda (liraglutide).
While lifestyle modifications, such as consuming a low-calorie diet and exercising, remain the foundation for effective weight loss, anti-obesity medications give hope to the many people struggling with managing their weight.
Table of Contents
Liraglutide: Setting the Standard
Liraglutide is in a class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists. Medications in this class act like your body’s naturally produced GLP-1 hormone. This hormone suppresses your appetite, increases satiety, and slows stomach emptying, so you feel full longer.
GLP-1 hormone also binds to receptors in the pancreas and stimulates insulin release. Insulin lowers glucose in the bloodstream by moving it into body cells, where it can be used for energy. Liraglutide treats diabetes and obesity.
Liraglutide: Clinical Trials
Liraglutide’s safety and efficacy were tested in the SCALE clinical trials. In the SCALE: Obesity and Prediabetes clinical trial, participants taking liraglutide lost about 7.4% of their body weight.
In the SCALE: Diabetes clinical trial, about 54% of the participants taking the 3.0 mg dose lost at least 5% of their body weight, and 25% lost at least 10%. About 40% of people taking liraglutide 1.8 mg and 21% taking a placebo lost at least 5% of their body weight.5
The SCALE: Maintenance clinical trial showed that people taking liraglutide, along with a reduced-calorie diet and exercise, could maintain or increase their weight loss while they continued to take liraglutide. 6
Summary: Average weight loss when taking liraglutide is 11 pounds with the 1.8 mg dose and 13–14 pounds with the 3.0 mg dose.
Semaglutide: A Game-Changer in Weight Loss
Semaglutide slows stomach emptying so you feel full longer, increases insulin secretion from the pancreas to reduce abnormally high blood sugar, and signals your brain that you are satisfied and no longer hungry.
Semaglutide Clinical Trials
The Semaglutide Treatment Effect in People with Obesity (STEP) trials evaluated the weight loss efficacy of semaglutide in individuals with diabetes and obesity.
In STEP 1, a randomized, double-blind trial, individuals with overweight or obesity who took semaglutide, along with a reduced-calorie diet and exercise, lost an average of 14.9% of their body weight.7
In STEP-2, a randomized, double-blind trial, semaglutide 2.4 mg once weekly resulted in an average weight loss of 9.6% from baseline after 68 weeks of treatment. The study included adults with type 2 diabetes mellitus, overweight or obesity, and HbA1c (a measurement of blood sugar over three months) of 7%–10%.8
In STEP 3, participants took semaglutide and received intensive behavioral therapy. They lost an average of 16% of their body weight. These results were similar to the STEP 1 results.9
STEP 4 demonstrated whether people taking semaglutide would maintain their weight loss or continue to lose weight. The group that took semaglutide continued to lose weight. In contrast, the group that stopped semaglutide regained some of their lost weight. This trial illustrates the need to treat obesity as a chronic disease.10
Average weight loss when taking semaglutide is 14% to 16%.
Tirzepatide: A Dual Receptor Agonist for Weight Loss
Tirzepatide is a novel dual-receptor agonist that activates both the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. By targeting both pathways, tirzepatide offers a synergistic effect on weight loss and blood sugar control. Its once-weekly dosing schedule makes it a convenient option for patients seeking long-term weight management.
Tirzepatide reduces blood sugar levels, improves insulin sensitivity, improves blood lipid levels, curbs hunger, increases satiety, and helps you feel full longer.
Tirzepatide Clinical Trials
The SURPASS clinical trials evaluated tirzepatide’s safety and efficacy in treating type 2 diabetes. The SURMOUNT clinical trials evaluated its weight-loss potential.
In the SURPASS-1 study, which was double-blind and placebo-controlled, people who took 5 mg, 10 mg, or 15 mg of tirzepatide once a week lost more weight than people who took a placebo after 40 weeks of treatment. Participants taking the highest dose, tirzepatide 15 mg, achieved an average weight loss of 11% from baseline.11
In SURPASS-2, tirzepatide 15 mg demonstrated a dose-dependent weight loss effect in participants with type 2 diabetes and obesity. The weight loss achieved with tirzepatide (15 mg) in SURPASS-2 was comparable to that of semaglutide (2.4 mg) in STEP-2.12
SURPASS-3 and 4 compared tirzepatide to insulin. Tirzepatide worked better than insulin in achieving glycemic control and weight loss.13,14
SURMOUNT-1: Over 2,000 adults with overweight or obesity took 5, 10, or 15 mg of tirzepatide and lost 15%, 19%, or 21% of their body weight at 72 weeks, respectively, compared to those who took a placebo. 15
SURMOUNT-2: Similar weight loss of 12–15% was seen with tirzepatide 10 mg and 15 mg doses in participants with obesity and type 2 diabetes. 16
SURMOUNT-3: Additional weight loss of 21% occurred with tirzepatide 15 mg plus lifestyle intervention over 12 weeks for a total weight loss of 26.6% of body weight over a total of 84 weeks.17
Tirzepatide led to an average weight loss of 11% to 25%.
Comparing semaglutide, liraglutide and tirzepatide
Semaglutide and liraglutide are very similar medications, with the most obvious difference being their dosage frequency. Tirzepatide is a GLP-1 receptor agonist, like semaglutide and liraglutide, but it is also a GIP receptor agonist. Targeting two receptors leads to even greater weight loss.
Weight loss injectables: Benefits
All three weight-loss injectables are GLP-1 receptor agonists and, therefore, can have the following benefits:
- Stimulates insulin release
- Inhibits glucagon release
- Slows stomach emptying
- Suppresses appetite
- Increases satiety after eating
- Decreases abdominal fat
- Decreases blood pressure
- Reduces LDL (bad) cholesterol
- Increases HDL (good) cholesterol
- Decreases triglycerides
- Decreases blood sugar
Weight Loss Efficacy
Semaglutide and tirzepatide can be best compared using the STEP 2 trial and the SURPASS 1 and 2 trials. In all three trials, the individuals enrolled had both obesity and type 2 diabetes. Typically, weight loss in people with type 2 diabetes is less than in people without the condition.
Semaglutide and tirzepatide both showed significant weight-loss efficacy in clinical trials. In the STEP-2 trial, participants taking semaglutide 2.4 mg achieved an average weight loss of 9.6% from baseline after 68 weeks of treatment. In comparison, participants taking tirzepatide 15 mg in SURPASS-1 and SURPASS-2 achieved weight losses of 10.1% and 13.1% from baseline, respectively. The weight loss achieved with both drugs exceeded the weight loss observed with pre-existing weight-loss medications.18
Both semaglutide and tirzepatide demonstrated improvements in glycemic control. Semaglutide 2.4 mg in the STEP-2 trial resulted in a reduction in HbA1c levels by more than 1% compared to placebo. Tirzepatide 15 mg in SURPASS-1 and SURPASS-2 led to even greater decreases in HbA1c levels, surpassing the efficacy of semaglutide. However, it is important to note that hypoglycemic (low blood sugar) events were reported with both drugs, albeit at a low rate.18
Both semaglutide and tirzepatide were generally well-tolerated in clinical trials, with gastrointestinal events being the most common adverse events reported. Nausea and diarrhea were the most frequently reported gastrointestinal events. The discontinuation rate due to adverse events was higher with both drugs compared to placebo.18
The most common side effects reported in weight loss drug clinical trials include:
- Stomach pain
Potential serious adverse effects associated with GLP-1 anti-obesity medications include:
- Diabetic retinopathy in people with type 2 diabetes
- Gallbladder disease
- Acute kidney injury
- Hypersensitivity or allergic reactions
- Thyroid cancer
- Injection site reactions
- Faster heart rate
- Low blood sugar
- Suicidal behavior or ideation
- Inflammation of the pancreas
- Intestinal blockage
All the GLP-1 drugs are fairly new, so this list may increase with increased drug use across populations.
Conclusion: What is the most effective weight loss injection?
Liraglutide, semaglutide, and tirzepatide are all three very effective prescription weight-loss medications. All three are FDA-approved anti-obesity medications that may also reduce the risk of cardiovascular disease.
All three medications can cause significant gastrointestinal side effects that improve over time. They are all expensive medications. They are not appropriate for all people, so it is essential to talk with a board-certified, licensed healthcare provider who has experience using these medications to learn more about the risk-versus-benefit profile of using these medications to treat obesity.
If you evaluate the medications in terms of their demonstrated weight-loss potential, then tirzepatide comes out as the winner.
Get started today with one of our Weight Loss Treatment Plans
- Yuen M, Lui D, Kaplan L. A systematic review and evaluation of current evidence reveals 195 obesity-associated disorders (OBAD). Obesity Week. 2016
- The Organization for Economic Co-operation and Development. Obesity Update 2017. https://www.oecd.org/health/health-systems/Obesity-Update-2017.pdf
- Stierman B, Afful, J., Carroll, M. D., Chen, T.-C., Davy, O., Fink, S., Fryar, C. D. H., Gu, Q., Hales, C. M., Hughes, J. P., Ostchega, Y., Storandt, R. J., & Akinbami, L. J. National Health and Nutrition Examination Survey 2017–March 2020 Prepandemic Data Files—Development of Files and Prevalence Estimates for Selected Health Outcomes. Vol. 158. 2021. https://www.cdc.gov/nchs/data/nhsr/nhsr158-508.pdf
- Panuganti KK, Nguyen M, Kshirsagar RK. Obesity. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459357/
- Davies MJ, Bergenstal R, Bode B, Kushner RF, Lewin A, Skjøth TV, Andreasen AH, Jensen CB, DeFronzo RA. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial. Jama.2015;314(7):687-699.
- Wadden TA, Hollander P, Klein S, Niswender K, Woo V, Hale PM, Aronne L. 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(11):1443-1451.
- Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, Lingvay I, McGowan BM, Oral TK, Rosenstock J, Wadden TA, Wharton S, Yokote K, Kushner RF. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab.2022;24(8):1553-1564.
- Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I. 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. The Lancet.2021;397(10278):971-984
- Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, Lingvay I, O’Neil PM, Rubino DM, Skovgaard D, Wallenstein SOR, Garvey WT, Investigators S. 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):1403-1413.
- Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, Lingvay I, Mosenzon O, Rosenstock J, Rubio MA, Rudofsky G, Tadayon S, Wadden TA, Dicker D. 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):1414-1425
- Forzano I, Varzideh F, Avvisato R, Jankauskas SS, Mone P, Santulli G. Tirzepatide: A Systematic Update. Int J Mol Sci. 2022;23(23).
- Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, Cui X, Brown K. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med.2021;385(6):503-515
- Ludvik B, Giorgino F, Jódar E, Frias JP, Fernández Landó L, Brown K, Bray R, Rodríguez Á. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet.2021;398(10300):583-598.
- Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, Aizenberg D, Wynne AG, Riesmeyer JS, Heine RJ, Wiese RJ. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet.2021;398(10313):1811-1824.
- Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine.2022;387(3):205-216.
- Frandsen CS, Madsbad S. SURMOUNT-2: new advances for treating obese type 2 diabetes with tirzepatide. The Lancet.2023;402(10402):586-588.
- Wadden TA, Chao AM, Machineni S, Kushner R, Ard J, Srivastava G, Halpern B, Zhang S, Chen J, Bunck MC, Ahmad NN, Forrester T. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nature Medicine.2023.
- Jung HN, Jung CH. The Upcoming Weekly Tides (Semaglutide vs. Tirzepatide) against Obesity: STEP or SURPASS? J Obes Metab Syndr. 2022 Mar 30;31(1):28-36. doi: 10.7570/jomes22012. PMID: 35314521; PMCID: PMC8987449.