Tirzepatide For Weight Loss Monday, March 11th, 2024
To deal with the marked rise in the prevalence of the obesity pandemic, there has been continuous ongoing research and development in the category of anti-obesity drugs.
Amongst the recent pharmacological interventions, Tirzepatide developed by Eli Lilly and company stands out as one of the safest drugs for obesity management. While this drug was initially introduced in the market for optimal glycemic control in patients with type 2 diabetes mellitus (T2DM), it soon started to gain attention for its potent weight loss effects in adults with obesity.
In this blog post, we will take a detailed dig into this peptide’s biochemical pathways that contribute to weight reduction and also talk about the dynamic interplay between metabolic regulation and body composition due to tirzepatide therapy.
How Does Tirzepatide For Weight Loss Work?
Its mechanism of action is rooted in its dual agonism of the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, leading to profound effects on metabolic regulation and body composition (1,2).
GLP-1 and GIP are incretin hormones secreted by the intestine in response to nutrient ingestion. These hormones play crucial roles in regulating glucose metabolism, insulin secretion, and satiety.
By acting as GLP-1 receptor agonist, Tirzepatide enhances glucose-dependent insulin secretion, leading to improved glycemic control (3). Additionally, it suppresses glucagon secretion, thereby reducing hepatic glucose production. These effects contribute to better glucose utilization and lower blood sugar levels, particularly in individuals with type 2 diabetes mellitus.
GLP-1 and GIP receptors are abundantly expressed in the brain, particularly in areas involved in appetite regulation. Activation of these receptors by Tirzepatide leads to increased feelings of satiety and reduced appetite, which can result in decreased food intake and subsequent body weight reduction.
Another mechanism by which Tirzepatide exerts its weight loss effects is through the inhibition of gastric emptying. By slowing down the rate at which food leaves the stomach, Tirzepatide prolongs the feeling of fullness after meals, further reducing calorie intake and promoting weight loss.
Beyond its effects on appetite and food intake, Tirzepatide also influences body composition. Clinical trials have demonstrated that treatment with Tirzepatide leads to a reduction in fat mass and preservation of lean body mass, suggesting a favorable shift in body composition conducive to chronic weight management.
While the primary mechanisms of Tirzepatide’s weight loss effects revolve around reducing calorie intake and improving metabolic regulation, there is emerging evidence suggesting that it may also impact energy expenditure (4). Further research is needed to elucidate the specific mechanisms through which Tirzepatide influences energy balance.
Benefits of Tirzepatide For Weight Loss
Clinical trials evaluating Tirzepatide have consistently demonstrated remarkable reductions in body weight among participants. Compared to placebo and other antidiabetic medications, Tirzepatide has been shown to induce substantial weight loss, with many individuals achieving clinically significant reductions in body mass index (BMI) and adiposity (5).
In addition to its weight loss effects, Tirzepatide exerts potent glycemic control, making it particularly advantageous for individuals with type 2 diabetes. By enhancing insulin secretion, suppressing glucagon release, and improving insulin sensitivity, Tirzepatide helps improve blood sugar levels while simultaneously promoting weight loss.
Beyond its effects on weight and glycemic control, Tirzepatide may confer cardiovascular benefits. Clinical trials have suggested a potential reduction in cardiometabolic risk factors, including a reduction in high blood pressure, lipid profiles, and markers of inflammation (6). These findings underscore the holistic impact of Tirzepatide on metabolic health and mitigate the risk of cardiovascular disease.
Weight loss achieved through Tirzepatide treatment is associated with improvements in various aspects of quality of life. Participants in clinical trials have reported enhancements in physical activity, vitality, and psychological well-being.
The alleviation of obesity-related comorbidities, such as joint pain, obstructive sleep apnea, and depression, further contributes to a better quality of life.
Unlike many fad diets or weight loss supplements that yield temporary results, Tirzepatide offers a pharmacological approach to chronic weight management that can be maintained. By addressing underlying metabolic dysregulation, Tirzepatide helps individuals achieve lasting improvements in weight and overall health.
How Much Time Does Tirzepatide Take To Cause Weight Loss?
The timeline for experiencing weight loss with Tirzepatide can vary among individuals and is influenced by factors such as baseline weight, metabolic health, adherence to treatment regimen, and lifestyle factors. However, clinical trials have provided insights into the typical timeframe for observing weight loss effects with Tirzepatide.
In studies evaluating Tirzepatide for weight loss in individuals with obesity or overweight, significant reductions in body weight have been observed within a relatively short period. For example, some participants experienced noticeable weight loss within the first few weeks to months of initiating Tirzepatide treatment (7).
In a Phase 2 clinical trial involving individuals with type 2 diabetes and obesity, participants receiving Tirzepatide experienced substantial weight loss compared to placebo within 12 weeks of treatment initiation. Moreover, weight loss continued to progress over the course of the trial, with participants achieving even greater body weight reduction by the end of the study period (7).
Similarly, in Phase 3 trials evaluating Tirzepatide for weight loss in individuals with obesity or overweight without diabetes, significant weight loss was observed within the first few months of treatment initiation. Participants typically achieved maximal weight loss within the first 6 to 12 months of treatment, with continued maintenance or further weight loss observed over longer durations of treatment (8,9).
It’s important to note that individual responses to Tirzepatide may vary, and some individuals may experience more rapid or gradual weight loss than others.
Additionally, adherence to the treatment regimen, diet, and exercise as well as other lifestyle factors can influence the rate and magnitude of weight loss achieved with Tirzepatide.
References:
Min T, Bain SC. The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials. Diabetes Ther. 2021 Jan;12(1):143-157. doi: 10.1007/s13300-020-00981-0. Epub 2020 Dec 15. PMID: 33325008; PMCID: PMC7843845
Frías JP. Tirzepatide: a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) dual agonist in development for the treatment of type 2 diabetes. Expert Rev Endocrinol Metab. 2020 Nov;15(6):379-394. doi: 10.1080/17446651.2020.1830759. Epub 2020 Oct 8. PMID: 33030356.
Thomas MK, Nikooienejad A, Bray R, Cui X, Wilson J, Duffin K, Milicevic Z, Haupt A, Robins DA. Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. J Clin Endocrinol Metab. 2021 Jan 23;106(2):388-396. doi: 10.1210/clinem/dgaa863. PMID: 33236115; PMCID: PMC7823251.
Christoffersen BØ, Sanchez-Delgado G, John LM, Ryan DH, Raun K, Ravussin E. Beyond appetite regulation: Targeting energy expenditure, fat oxidation, and lean mass preservation for sustainable weight loss. Obesity (Silver Spring). 2022;30(4):841-857. doi:10.1002/oby.23374
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038
Sattar N, McGuire DK, Pavo I, et al. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022;28(3):591-598. doi:10.1038/s41591-022-01707-4
Min T, Bain SC. The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials. Diabetes Ther. 2021;12(1):143-157. doi:10.1007/s13300-020-00981-0
Rosenstock J, Wysham C, Frías JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial [published correction appears in Lancet. 2021 Jul 17;398(10296):212]. Lancet. 2021;398(10295):143-155. doi:10.1016/S0140-6736(21)01324-6
Lingvay I, Cheng AY, Levine JA, et al. Achievement of glycaemic targets with weight loss and without hypoglycaemia in type 2 diabetes with the once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide: A post hoc analysis of the SURPASS-1 to -5 studies. Diabetes Obes Metab. 2023;25(4):965-974. doi:10.1111/dom.14943
