Thread for Tirzepatide studies and personal experiences

[MR. BMJ]

We have one for Semaglutide, so I figured we might as well throw one up for tirzepatide as well. They are both GLP-1 agonists, but tirzepatide has a dual-action in that it also acts as a glucose-dependent insulinotropic polypeptide (GIP) drug.

Here is a newer meta-analysis below. Feel free to add experiences if yuou have used this drug, as well as any future studies done on it. There are a few I may have already posted here to TID, and I know there were some we had over at WCBB. If I get time, i'll add those in here. Anyway......,

*************************************************************

Full text of the study in link:

Weight loss efficiency and safety of tirzepatide: A Systematic review

Tirzeptide is a novel glucagon-like peptide-1 receptor (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) drug, which shows good efficiency for weight loss. Therefore, we aim to investigate the efficacy and safety of tirzepatide for weight ...

www.ncbi.nlm.nih.gov

Meta-Analysis. PLoS One. 2023 May 4;18(5):e0285197.

Weight loss efficiency and safety of tirzepatide: A Systematic review​

Fei Lin 1 2, Bin Yu 3, Baodong Ling 4, Guangyao Lv 5, Huijun Shang 6, Xia Zhao 1 2, Xiaoling Jie 1 2, Jing Chen 1 2, Yan Li 1 2

Abstract​

Objective: Tirzeptide is a novel glucagon-like peptide-1 receptor (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) drug, which shows good efficiency for weight loss. Therefore, we aim to investigate the efficacy and safety of tirzepatide for weight loss in type 2 diabetes mellitus (T2DM) and obesity patients in this meta-analysis study.

Methods: Cochrane Library, PubMed, Embase, Clinical Trials, and Web of Science were searched from inception to October 5, 2022. All randomized controlled trials (RCTs) were included. The odds ratio (OR) was calculated using fixed-effects or random-effects models by Review Manager 5.3 software.

Results: In total, ten studies (12 reports) involving 9,873 patients were identified. A significant loss body weight in the tirzepatide group versus the placebo by -9.81 kg (95% CI (-12.09, -7.52), GLP-1 RAs by -1.05 kg (95% CI (-1.48, -0.63), and insulin by -1.93 kg (95% CI (-2.81, -1.05), respectively. In sub-analysis, the body weight of patients was significantly reduced in three tirzepatide doses (5 mg, 10 mg, and 15 mg) when compared with those of the placebo/GLP-1 RA/insulin. In terms of safety, the incidence of any adverse events and adverse events leading to study drug discontinuation was higher in the tirzepatide group, but the incidence of serious adverse events and hypoglycaemia was lower. Additionally, the gastrointestinal adverse events (including diarrhea, nausea, vomiting and decreased appetite) of tirzepatide were higher than those of placebo/basal insulin, but similar to GLP-1 RAs.

Conclusion: In conclusion, tirzeptide can significantly reduce the weight of T2DM and patient with obesity, and it is a potential therapeutic regimen for weight-loss, but we need to be vigilant about its gastrointestinal reaction.

 

[LITTLEMAGS]

Great stuff

 

[MR. BMJ]

The incretin co-agonist tirzepatide requires GIPR for hormone secretion from human islets - Nature Metabolism

This study shows that the insulinotropic actions of the dual GIPR and GLP-1R agonist, tirzepatide, depend on GIPR, and that tirzepatide has weaker activity at the mouse GIPR than murine GIP.

www.nature.com

That link has the full study.

How it works in regard to the pancreas and insulin:

“Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) mediate insulin responses that are proportionate to nutrient intake to facilitate glucose tolerance.

These data demonstrate that tirzepatide stimulates #insulin secretion from human islets through both incretin receptors.”

*********************************************

The incretin co-agonist tirzepatide requires GIPR for hormone secretion from human islets​

Abstract​

The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) mediate insulin responses that are proportionate to nutrient intake to facilitate glucose tolerance1. The GLP-1 receptor (GLP-1R) is an established drug target for the treatment of diabetes and obesity2, whereas the therapeutic potential of the GIP receptor (GIPR) is a subject of debate. Tirzepatide is an agonist at both the GIPR and GLP-1R and is a highly effective treatment for type 2 diabetes and obesity3,4. However, although tirzepatide activates GIPR in cell lines and mouse models, it is not clear whether or how dual agonism contributes to its therapeutic benefit. Islet beta cells express both the GLP-1R and the GIPR, and insulin secretion is an established mechanism by which incretin agonists improve glycemic control5. Here, we show that in mouse islets, tirzepatide stimulates insulin secretion predominantly through the GLP-1R, owing to reduced potency at the mouse GIPR. However, in human islets, antagonizing GIPR activity consistently decreases the insulin response to tirzepatide. Moreover, tirzepatide enhances glucagon secretion and somatostatin secretion in human islets. These data demonstrate that tirzepatide stimulates islet hormone secretion from human islets through both incretin receptors.

 

[Tuffoldman]

I have used both and in addition to that I've used Lirglutide which is also a GLP1.

Have run all three of those and semi-glutide is still the best based on similar milligrams per week. I assumed because tirzepatide was working from two different angles as far as controlling blood sugar and insulin that would be more effective. Based on those clinical trials and everything that I've read in theory it should be as well as their clinical trial says it is but from my experience semiglutide still works better at the same dosing. tirzepatide works better if you increase the dose but dollar to pounds semiglutide is the better way to go.


Lirglutide is inexpensive but does not curb hunger as long or as effective. My wife and I do daily doses instead of weekly doses. The difference is doing weekly doses at a high enough amount to be fully effective you end up with the side effects of itchy skin and rash if you're susceptible to that. Doing it daily it's not quite as prominent is what we found. Now the flip side is the first week it's not as effective because you don't have as big a dose but once you get past that week Mark is just like you're taking it weekly so to speak. The other problem with doing it once a week is you have a high point just like any other shot and then as the time goes by it weekends so by the day six or seven it's not as effective.

We don't use it to lose weight we use it in a way to control cravings so we try and only eat healthier foods not necessarily trying to use it to drop tons of weight.


That's my take

 

[Wilson6]

I have used both and in addition to that I've used Lirglutide which is also a GLP1.

Have run all three of those and semi-glutide is still the best based on similar milligrams per week. I assumed because tirzepatide was working from two different angles as far as controlling blood sugar and insulin that would be more effective. Based on those clinical trials and everything that I've read in theory it should be as well as their clinical trial says it is but from my experience semiglutide still works better at the same dosing. tirzepatide works better if you increase the dose but dollar to pounds semiglutide is the better way to go.


Lirglutide is inexpensive but does not curb hunger as long or as effective. My wife and I do daily doses instead of weekly doses. The difference is doing weekly doses at a high enough amount to be fully effective you end up with the side effects of itchy skin and rash if you're susceptible to that. Doing it daily it's not quite as prominent is what we found. Now the flip side is the first week it's not as effective because you don't have as big a dose but once you get past that week Mark is just like you're taking it weekly so to speak. The other problem with doing it once a week is you have a high point just like any other shot and then as the time goes by it weekends so by the day six or seven it's not as effective.

We don't use it to lose weight we use it in a way to control cravings so we try and only eat healthier foods not necessarily trying to use it to drop tons of weight.


That's my take

Clinically semaglutide and other GLP-1s are likely more efficacious with more frequent micro dosing (less sides), but the general population couldn't handle more frequent injections and the FDA would want more studies to approve that dosing.

 

[Tuffoldman]

Clinically semaglutide and other GLP-1s are likely more efficacious with more frequent micro dosing (less sides), but the general population couldn't handle more frequent injections and the FDA would want more studies to approve that dosing.

I didn't know that the more frequent doses is better as far as the effectivity but it works better for me and I'm a pincushion and have been for many many years so extra shots aren't that big a deal

 

[MR. BMJ]

Not fan at all on "Self-reporting." But......
**************************************************

Tirzepatide in Hispanic/Latino Patients With Type 2 Diabetes: A Subgroup Analysis of the SURPASS Program

AbstractContext. Efficacy and safety of tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonis

academic.oup.com

Tirzepatide in Hispanic/Latino Patients with Type 2 Diabetes: A Subgroup Analysis of the SURPASS program
The Journal of Clinical Endocrinology & Metabolism, dgad495, https://doi.org/10.1210/clinem/dgad495
Published:

21 August 2023

Abstract​

Context
Efficacy and safety of tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, have been studied in patients with type 2 diabetes in the global phase 3 SURPASS program.

Objective
To assess the efficacy and safety of tirzepatide in Hispanic/Latino and non-Hispanic/Latino patients in SURPASS-1 to -4 clinical trials.

Design
Exploratory analysis of SURPASS-1 to -4 trial data
Participants
5679 patients were included; 2895 self-reported Hispanic/Latino ethnicity

Interventions
Tirzepatide 5, 10, or 15 mg, placebo, or active comparator (semaglutide 1 mg, insulin degludec, and insulin glargine).

Main Outcome Measures
Change in hemoglobin A1c (HbA1c) and body weight from baseline to week 40 (SURPASS-1 and -2) and to week 52 (SURPASS-3 and -4), and other efficacy and safety outcomes were evaluated within Hispanic/Latino and non-Hispanic/Latino subgroups.

Results
Among Hispanic/Latino and non-Hispanic/Latino patients treated with tirzepatide, respectively, HbA1c decreased significantly from baseline, ranging from 1.9% to 2.7% and 1.7% to 2.5%, and body weight decreased significantly from baseline, ranging from 5.3 kg to 12.4 kg and 6.5 kg to 17.1 kg (both P < 0.05) versus comparators across all trials. Subgroup trends were consistent with the overall trial populations. Treatment-emergent adverse events were reported in similar proportions across the subgroups and were primarily gastrointestinal disorders. The incidence of hypoglycemia was low.

Conclusions
Tirzepatide significatively reduced HbA1c and body weight in Hispanic/Latino and non-Hispanic/Latino patients. Tirzepatide was generally well tolerated in both subgroups. Efficacy and safety trends were comparable between subgroups and with the overall trial populations.

 

[MR. BMJ]

Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial - Nature Medicine

In the SURMOUNT-3 trial, once-weekly treatment with tirzepatide was demonstrated to result in clinically meaningful additional weight loss in adults with overweight or obesity following initial successful weight loss of at least 5% body weight with intensive lifestyle intervention.

www.nature.com

(Full Text)

Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial​

Nature Medicine (2023); Published: 15 October 2023

Abstract​

The effects of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, on weight reduction after successful intensive lifestyle intervention are unknown. This double-blind, placebo-controlled trial randomized (1:1) adults with body mass index ≥30 or ≥27 kg/m2 and at least one obesity-related complication (excluding diabetes), who achieved ≥5.0% weight reduction after a 12-week intensive lifestyle intervention, to tirzepatide maximum tolerated dose (10 or 15 mg) or placebo once weekly for 72 weeks (n = 579). The treatment regimen estimand assessed effects regardless of treatment adherence in the intention-to-treat population. The coprimary endpoint of additional mean per cent weight change from randomization to week 72 was met with changes of −18.4% (standard error (s.e.) 0.7) with tirzepatide and 2.5% (s.e. 1.0) with placebo (estimated treatment difference −20.8 percentage points (95% confidence interval (CI) −23.2%, −18.5%; P < 0.001). The coprimary endpoint of the percentage of participants achieving additional weight reduction ≥5% was met with 87.5% (s.e. 2.2) with tirzepatide and 16.5% (s.e. 3.0) with placebo achieving this threshold (odds ratio 34.6%; 95% CI 19.2%, 62.6%; P < 0.001). The most common adverse events with tirzepatide were gastrointestinal, with most being mild to moderate in severity. Tirzepatide provided substantial additional reduction in body weight in participants who had achieved ≥5.0% weight reduction with intensive lifestyle intervention.

 

[rolldice]

Dumbed down question. What is common dosing for this?

 

[NuSciencePeptides]

Dumbed down question. What is common dosing for this?

2.5 mg/0.5 mL, 5 mg/0.5 mL, 7.5 mg/0.5 mL, 10 mg/0.5 mL, 12.5 mg/0.5 mL, 15 mg/0.5 mL

 

[rolldice]

2.5 mg/0.5 mL, 5 mg/0.5 mL, 7.5 mg/0.5 mL, 10 mg/0.5 mL, 12.5 mg/0.5 mL, 15 mg/0.5 mL

Yes but what is recommended dose

 

[Wilson6]

There was a piece on TZ vs Sema last night on the news, was working with clients so didn't catch everything but the comparison showed TZ to be superior short and longer term (1 yr) with weight loss. I really want to see a longer term study on any GLP-1 drug using iDXA. What is happening with lean mass and bone density over time particularly in subjects that exercise, consume adequate macros and protein. Sure you lose fat, but at what expense?