Tirzepatide Powder

What Is Tilsiparatide?

Tirzepatide powder is a once-weekly dual agonist of glucose-dependent insulinotropic peptide (GIP, also known as gastric inhibitory peptide) receptor and glucagon-like peptide-1 (GLP-1) receptor. Both GIP and GLP-1 are hormones secreted by the intestine and can promote insulin secretion. Tirzepatide combines two insulinotropic effects into a single molecule and represents a new class of drugs for the treatment of type 2 diabetes.
Tirzepatide is a GIP/GLP-1 dual receptor agonist with a half-life of about 5 days and can be administered once a week. The SURPASS trial showed that tilsiparatide provided clinically meaningful improvements in glycemic control and weight loss with a favorable safety profile.
Based on this, the latest consensus statement issued by the American Diabetes Association and the European Association for the Study of Diabetes classifies tilsiparatide as the most effective treatment for blood sugar control and weight loss.
Tirzepatide is the first dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. Tirzepatide is administered as a once-weekly subcutaneous injection, and the dose can be adjusted based on tolerance. According to its SURPASS series of studies, the highest dose of 15 mg can significantly further reduce the absolute value of HbA1C by 1.6% compared with placebo. In addition to its hypoglycemic effect, the SURMOUNT-1 study on obese patients without diabetes showed that Tirzepatide at the highest dose of 15 mg could significantly reduce the patient's weight by an average of 22.5% (24 kg). It is currently the only weight loss drug that reduces weight by more than 20%.

Why Can Hypoglycemic Drugs Also Help You Lose Weight?

The first thing to understand is that not all anti-diabetic drugs can help you lose weight. Metformin, the first-line drug of choice for type 2 diabetes worldwide, does have a moderate weight loss effect, but there are also many diabetes drugs that have weight gain effects.

Tirsiparatide improves glycemic control by activating GLP-1 and GIP receptors. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are hormones involved in blood sugar control. GLP-1's main effect is to suppress appetite by regulating insulin secretion and delaying gastric emptying. GIP gastric inhibitory peptide mainly inhibits gastric acid secretion and gastric motility, and also has certain effects on protecting pancreatic islets and adjusting insulin secretion. Therefore, to put it simply, after this drug enters the human body, it has a dual effect of suppressing appetite.

Judging from the recently disclosed data, tilsiparatide has the most significant weight loss effect in history and is also the first drug with an average weight loss effect of more than 20% of body weight. In the phase 3 clinical trial, after 72 weeks of tilsiparatide, the average weight loss proportions of subjects in the low-dose (5mg), medium-dose (10mg), and high-dose groups (15mg) were 15%, 19.5%, and 20.9%, respectively. , compared with 3.1% in the placebo group. In the mid- and high-dose groups, 50.1% and 56.7% had weight loss of more than 20% respectively. At the same time, the safety profile of several dose groups was very good, and the frequency of adverse reactions was comparable to that of the placebo group.

Experiments On Weight Loss

SURMOUNT-1 Test
The SURMOUNT-1 trial included 2539 adults who did not have type 2 diabetes, were obese or overweight, and had at least 1 comorbidity. The mean baseline weight was 104.8 kg and the mean BMI was 38 kg/m2. Patients were randomized 1:1:1:1 to receive Zepbound 5 mg, 10 mg, 15 mg, or placebo as subcutaneous injections once weekly for 72 weeks. The primary endpoints were percent change in body weight from baseline and the proportion of patients who lost at least 5% of their body weight at 72 weeks. In the SURMOUNT-1 trial, Zepbound was associated with the following weight loss compared with placebo at week 72:
①Average weight loss: 15% (5mg), 19.5% (10mg), 20.9% (15mg) VS 3.1% (placebo).
②Percentage of patients who lost at least 5% of their body weight: 85.1% (5mg), 88.9% (10mg), 90.9% (15mg) VS 34.5% (placebo).

SURMOUNT-2 Test
The SURMOUNT-2 trial included 938 adults with type 2 diabetes who were obese or overweight. The mean baseline weight was 100.7 kg and the mean BMI was 36.1 kg/m2. Patients were randomly assigned in a 1:1:1 ratio to receive Zepbound 10 mg, 15 mg, or placebo as subcutaneous injections once weekly for 72 weeks. The primary endpoints were percent change in body weight from baseline and the proportion of patients who lost at least 5% of their body weight at 72 weeks. Results showed that Tirzepatide (10mg and 15mg) achieved greater weight loss than placebo at 72 weeks of treatment. The study met the co-primary endpoint and all key secondary endpoints compared to placebo. Compared with placebo (3.3%, 3.2 kg), patients in the 10 mg group lost an average of 13.4% (13.5 kg) and those in the 15 mg group lost an average of 15.7% (15.6 kg).

Additionally, 81.6% (10 mg) and 86.4% (15 mg) of those taking tilsiparatide lost at least 5% of their body weight (another co-primary endpoint), compared with 30.5% of those taking placebo. Reduced.

Experimental Data On Lowering Blood Sugar

The results of the SURPASS-AP-Combo trial show that weekly use of tilsiparatide can significantly improve blood sugar control in patients with type 2 diabetes (T2D) whose blood sugar is still poorly controlled using metformin and is well tolerated.

One of the main advantages of this trial is that most of the enrolled patients are from China, the sample size is large, the completion rate is high, and the data provided are very complete. Therefore, the test results have high generalizability to clinical practice in my country.

The trial screened T2D patients (≥18 years old) who did not receive insulin treatment in 66 hospitals in China, South Korea, Australia and India. A total of 917 patients were finally enrolled (763 of them were from China) on a 1:1 basis: Randomly assigned to 4 groups in a 1:1 ratio:

Tirsiparatide 5 mg weekly (n = 230);
tilsiparatide 10 mg weekly (n = 228);
tilsiparatide 15 mg weekly (n = 229);
Daily insulin glargine group (n = 230).

The primary endpoint of the study was non-inferiority mean change in HbA1c.

The results of the study showed that from baseline to week 40, patients taking tilsiparatide had a better least squares mean (s.e) reduction in HbA1c than patients taking insulin glargine, regardless of dose.

Declining trend of HbA1c in each group of patients at different time points

Compared with the insulin glargine group, the proportion of patients in the tilsiparatide 5 mg group, 10 mg group, and 15 mg group achieved HbA1c < 7.0% at week 40 was higher, 75.4%, 86.0%, and 84.4%, respectively.

Proportion of patients achieving HbA1c <7.0%, ≤6.5%, <5.7% goals at 40 weeks

At week 40, patients in all tilsiparatide dose groups demonstrated significant weight loss, and a higher proportion of patients in all tilsiparatide dose groups achieved their weight loss goals compared with those in the insulin glargine group. .

Proportion of patients achieving weight loss goal at 40 weeks

The trial noted that common adverse reactions of tilsiparatide were mild to moderate loss of appetite, diarrhea and nausea, with no reports of severe hypoglycemia.

Overall, the SURPASS-AP-Combo trial is consistent with the results reported in previous SURPASS series trials, confirming the efficacy and safety of tsiparatide in the T2D population in the Asia-Pacific region, mainly Chinese patients.
Not only does tilsiparatide show a better HbA1c-lowering effect than insulin glargine, but is generally well tolerated, it can also improve insulin sensitivity and help enhance the anti-hyperglycemic effect.

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