Tirzepatide

What is tirzepatide and how does it work?

Tirzepatide is a long-acting peptide that mimics two gut hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). According to the EMA product information, its effect at the GIP receptor is similar to native GIP, and its effect at the GLP-1 receptor is weaker than native GLP-1. Both receptors are found in the hormone-secreting cells of the pancreas and in the appetite-regulating regions of the brain. ^[3]

Its effect on blood sugar comes through several routes: it increases insulin secretion in a glucose-dependent manner, improves insulin sensitivity, reduces glucagon and delays gastric emptying. Its effect on weight is largely explained by decreased appetite and increased feeling of fullness; the product information states that the weight loss is mostly from fat mass. ^[3]

The Türkiye SmPC (KÜB) writes that the molecule carries a fatty acid chain enabling it to bind albumin and that its elimination half-life is about 5 days; this is the rationale for weekly administration. ^[1] The shared properties of the GLP-1 class and differences from other medicines in the class are covered in the general guide: GLP-1 agonists.

Are Mounjaro and Zepbound the same medicine?

The active substance is the same; the name varies by country and licensed use.

• US: Mounjaro is licensed for blood sugar control in type 2 diabetes in people aged 10 and over and for reducing major cardiovascular events in adults with high-risk type 2 diabetes. ^[5] Zepbound is licensed for weight reduction and long-term maintenance in obesity or in overweight adults with at least one weight-related disease, and for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity. ^[4]
• European Union: Under the name Mounjaro there are both a type 2 diabetes (age 10 and over) and a weight management indication; the results of the sleep apnea and heart failure trials appear in section 5.1 of the product information. ^[3]
• Türkiye: Under the name Mounjaro there are indications for type 2 diabetes and weight control in adults. ^[1]

Is Mounjaro licensed in Türkiye?

In the TİTCK (Turkish Medicines and Medical Devices Agency) Licensed Human Medicinal Products List (October 16, 2026), two forms with the active substance tirzepatide appear: a single-dose 0.5 mL solution for injection of 2.5, 5, 7.5, 10, 12.5 and 15 mg (first license date August 15, 2024) and a 4-dose KwikPen ready-to-use pen in the same doses (first license date March 26, 2025). ^[2]

According to the KwikPen SmPC (KÜB; approval March 6, 2026), Mounjaro is indicated in two situations: ^[1]

• Type 2 diabetes: in adults whose diabetes is inadequately controlled, as an addition to diet and exercise; alone where metformin is unsuitable, or in addition to other diabetes medicines. The Türkiye SmPC excludes DPP-4 inhibitors and other GLP-1 receptor analogues from this addition.
• Body weight control: in addition to a low-calorie diet and increased physical activity, in adults with an initial BMI of 30 kg/m² and above, or between 27–30 kg/m² with at least one weight-related disease such as hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease, prediabetes or type 2 diabetes.

Two differences between the Türkiye SmPC and the EMA product information stand out. First, the Türkiye SmPC regards the medicine as contraindicated in patients with medullary thyroid carcinoma in themselves or in their family history and with multiple endocrine neoplasia type 2 (MEN 2) syndrome; in the contraindications section of the EMA product information only hypersensitivity appears. ^{[1] [3]} Second, according to the Türkiye SmPC, safety and efficacy have not been established under age 18; in the EU there is a type 2 diabetes indication for ages 10 and over. The prescription type is not specified in the official documents reviewed; this guide makes no such distinction. In the EK-4/A List of Medicines to Be Reimbursed published in the Official Gazette (Resmî Gazete) on April 8, 2026 by SGK (Social Security Institution), no tirzepatide-containing product appears. ^[15]

Is use for weight loss off-label?

In Türkiye, weight control is one of Mounjaro’s licensed indications; however, this indication depends on the BMI criteria above and adult age. ^[1] Use outside these criteria, for example cosmetic weight loss in someone with a BMI below 27 kg/m², or weight treatment under age 18, falls outside the scope of the SmPC.

In June 2024, the EMA stated that use of GLP-1 receptor agonists for cosmetic weight loss in people without obesity or without weight-related health problems was frequently mentioned in the press and on social media and was worsening existing supply shortages. According to the same statement, high demand has attracted criminal activity and increased the risk of counterfeit products. ^[14] This statement is aimed at the GLP-1 class in general; the supply recommendations at that time did not cover Mounjaro.

How much does it lower blood sugar in type 2 diabetes?

According to the EMA product information, tirzepatide was compared with placebo or active medicines (semaglutide, insulin degludec, insulin glargine) in five randomized phase 3 trials (SURPASS 1–5; 6,263 patients in total, 4,199 in the tirzepatide arms); in all trials HbA1c fell more than with placebo or the comparator. ^[3]

In SURPASS-2, nausea was reported in 17–22% in the tirzepatide arms and 18% in the semaglutide arm; serious adverse events in 5–7% in the tirzepatide arms and 3% in the semaglutide arm. The trial was funded by the manufacturer of tirzepatide. ^[7]

How much weight does it cause to be lost in obesity?

The core evidence in adults without diabetes is SURMOUNT-1: 2,539 people with a BMI of 30 and above, or 27 and above with at least one weight-related disease, received tirzepatide (5, 10 or 15 mg) or placebo for 72 weeks in addition to low-calorie diet and physical activity counseling. ^[8]

Mean values do not mean that everyone will lose this much weight: in SURMOUNT-1, even in the 15 mg arm about one in ten participants did not reach the 5% threshold (loss of 5% and above was 91%). Discontinuation because of adverse events was 4.3%, 7.1% and 6.2% at 5, 10 and 15 mg; 2.6% with placebo. ^[8] According to the EMA product information, in SURMOUNT-1, 1,032 participants with prediabetes were followed for up to 176 weeks; at the end of this period, progression to type 2 diabetes was 1.2% in the tirzepatide arms and 12.6% in the placebo arm. ^[3]

What came out of the direct comparison with semaglutide?

SURMOUNT-5 is an open-label phase 3b trial comparing tirzepatide (highest tolerated dose 10 or 15 mg) with semaglutide (1.7 or 2.4 mg) in 751 adults with obesity without diabetes. At week 72, mean weight change was −20.2% with tirzepatide and −13.7% with semaglutide; the reduction in waist circumference was 18.4 cm versus 13.0 cm. ^[9] The EMA product information gives −21.6% versus −15.4% (difference −6.2 points) with a different analysis for the same trial. ^[3]

This is a single trial; participants and physicians knew which medicine was given, and the trial was funded by the manufacturer of tirzepatide. ^[9] The evidence and safety profile of semaglutide itself are in a separate guide: Semaglutide.

Is there evidence for the heart, sleep apnea and heart failure?

There is one large trial in each of these three areas; regulatory bodies have carried the results into product information differently.

Does it reduce cardiovascular events?

SURPASS-CVOT compared tirzepatide (up to 15 mg) with dulaglutide 1.5 mg in 13,299 patients with type 2 diabetes and atherosclerotic cardiovascular disease; dulaglutide is a medicine shown to reduce cardiovascular events, that is, the comparison is against an active medicine, not placebo. The composite of cardiovascular death, heart attack or stroke was 12.2% in the tirzepatide arm and 13.1% in the dulaglutide arm (HR 0.92; 95.3% CI 0.83–1.01). Tirzepatide was shown to be non-inferior to dulaglutide; superiority was not shown (P = 0.09). ^[10]

The bodies handled this result differently. In the US, an indication for reducing major cardiovascular events in adults with high-risk type 2 diabetes was added to the Mounjaro label. ^[5] The EMA accepted that Mounjaro reduces the risk of serious cardiovascular events in this group, but did not propose a separate indication on the grounds that this use is already within the scope of the type 2 diabetes indication; it added the data to the product information. ^[6] SURPASS-CVOT data do not appear in the Türkiye SmPC (KÜB) reviewed (March 6, 2026). ^[1]

Does it have an effect on sleep apnea?

In the two trials in the SURMOUNT-OSA program, 469 adults with moderate-to-severe obstructive sleep apnea and obesity received tirzepatide (10 or 15 mg) or placebo for 52 weeks; people with type 2 diabetes were not enrolled. According to the product information, the apnea-hypopnea index (the number of breathing stops and reductions per hour) fell by 22.5 more events per hour than placebo in those not using positive airway pressure (PAP) and by 24.4 more in those using PAP. The EMA notes that the second trial does not allow a conclusion about additional benefit on top of PAP, because PAP was stopped 7 days before measurement. ^[3] In the US, Zepbound is licensed for this use. ^[4]

What is known in heart failure?

In the SUMMIT trial, 731 patients with heart failure with preserved ejection fraction and obesity were followed for a median of 104 weeks. According to the EMA product information, cardiovascular death or a heart failure event was 9.9% in the tirzepatide arm and 15.3% in the placebo arm (HR 0.62; 0.41–0.95); the difference came from heart failure events (HR 0.54), and no reduction was seen in cardiovascular death (in the product information 2.7% versus 1.4%; HR 1.99, 0.68–5.81). ^[3] This result appears in the EU product information; the US labels reviewed and the Türkiye SmPC (KÜB) do not include this trial. ^{[4] [1]}

Does weight come back when it is stopped?

It does; how much will return varies from person to person. In SURMOUNT-4, 670 participants who received open-label tirzepatide for 36 weeks and lost a mean of 20.9% were randomly assigned either to continue treatment or to switch to placebo. Over the following 52 weeks, those who switched to placebo regained a mean of 14.0%, those who continued lost a further 5.5%; those who maintained at least 80% of the loss were 16.6% versus 89.5%. The placebo group was still a mean of 9.9% below baseline weight at week 88. ^[11]

Detailed guideWhat happens when Mounjaro is stopped? Weight regain and what is known→

How is Mounjaro used? What does the SmPC (KÜB) say?

The Türkiye SmPC (KÜB) states that tirzepatide is administered subcutaneously (abdomen, thigh or upper arm) once a week and can be given at any time of day, with or without food. According to the SmPC, the starting dose is 2.5 mg once a week and is raised to 5 mg after 4 weeks; if needed, increments of 2.5 mg can be made at intervals of at least 4 weeks, and the highest dose is 15 mg per week. ^[1] This information is product information written for physicians; the dose appropriate to the person and the dose increase are determined by the physician. The missed dose rule, storage conditions and the difference between forms are on a separate page.

Detailed guideHow is Mounjaro used? Dose steps, storage and forms according to the SmPC (KÜB)→

What are the side effects and serious risks?

Digestive side effects are the most common. In the weight trial in people without diabetes, gastrointestinal disorders were 55.6%, 60.8% and 59.2% at 5, 10 and 15 mg; 30.3% with placebo. Nausea, vomiting and diarrhea were more frequent during the dose-escalation period and decreased over time. ^[1]

The serious risks that stand out in the product information are as follows:

• Thyroid C-cell tumors: In rats, tirzepatide caused thyroid C-cell tumors; it is not known whether it causes medullary thyroid carcinoma in humans. The FDA gives this as a boxed warning. ^[4] The Türkiye SmPC (KÜB) regards use as contraindicated in personal or familial medullary thyroid carcinoma and MEN 2. ^[1]
• Acute pancreatitis: It has been reported in people using tirzepatide; it has not been studied in people with a history of pancreatitis. If suspected the medicine is stopped, and if the diagnosis is confirmed it is not restarted. ^[1]
• Gallbladder disease: Cholelithiasis and cholecystitis are among the uncommon side effects in the SmPC (KÜB); in the weight trials, acute gallbladder events were associated with weight loss. ^[1]
• Hypoglycemia: The risk increases when used with a sulfonylurea or insulin; the SmPC (KÜB) writes that a reduction in the dose of these medicines may be considered. ^[1]
• Fluid loss and kidney: Fluid loss due to nausea, vomiting and diarrhea can lead to worsening kidney function up to acute kidney failure; it is particularly important in older people. ^[1]
• Aspiration during anesthesia: Cases of aspiration into the lungs during general anesthesia or deep sedation have been reported in people using GLP-1 receptor agonists; delayed gastric emptying is taken into account before the procedure. ^[1]

Frequency tables, discontinuation rates, hair loss and muscle loss data are on the side effects page.

Detailed guideMounjaro side effects: frequencies, serious risks and discontinuation rates→

In whom is it not used or is caution needed?

• Pregnancy and pregnancy planning: The Türkiye SmPC (KÜB) gives the pregnancy category as C; animal studies have shown reproductive toxicity. It is not recommended in pregnancy and in women of childbearing age not using contraception; because of the long half-life, it must be stopped at least 1 month before planned pregnancy. ^[1]
• Breastfeeding: According to the Türkiye SmPC (KÜB), it is not known whether it passes into breast milk, and the decision is made according to the benefit-risk balance. The EMA’s current product information, however, writes that after a single 5 mg dose undetectable or very low levels were found in milk and that use during breastfeeding may be considered. ^{[1] [3]}
• Oral contraceptive pills: A single dose of tirzepatide lowered the blood level of the pill. The EMA and the Türkiye SmPC (KÜB) do not regard this decrease as clinically significant. The FDA label, however, recommends that people using oral hormonal contraceptives switch to a non-oral method or add a barrier method for 4 weeks after the start of treatment and after each dose increase. ^{[1] [4]}
• Other oral medicines: Delayed gastric emptying can affect the rate of absorption of medicines; for medicines with a narrow therapeutic range such as warfarin and digoxin, monitoring is recommended particularly at the start and with dose increases. ^[1]
• Diabetic retinopathy and severe gastrointestinal disease: According to the Türkiye SmPC (KÜB), it has not been studied in retinopathy requiring acute treatment and in severe gastrointestinal disease including severe gastroparesis; cautious use is recommended. ^[1] The EMA product information writes that rapid improvement in blood sugar has been associated with temporary worsening of diabetic retinopathy and that people with retinopathy should be closely monitored. ^[3]

Why are counterfeit, illegal and “compounded” tirzepatide risky?

According to a joint statement by the EMA and European medicines authorities (September 2025), a sharp rise was seen in illegal products marketed as semaglutide, liraglutide and tirzepatide; these products are mostly sold through fake websites and social media, are unlicensed and do not meet quality, safety and efficacy standards. The statement says these products may not contain the claimed active substance at all or may contain other substances at harmful levels. ^[13]

In Türkiye, a letter sent by the Erzurum Provincial Health Directorate to the pharmacists’ chamber (chamber registration date May 20, 2026), referring to a TİTCK letter dated May 14, 2026, reports that notifications of suspected counterfeiting in medicines containing GLP-1 receptor agonists have risen sharply; it states that in pharmacy and drug warehouse inspections Ozempic, Saxenda and Wegovy pens and Mounjaro solution for injection carried a high counterfeiting risk. The letter stresses that medicines should not be bought over the internet and that medicines that cannot be registered in the Medicine Tracking System (İlaç Takip Sistemi, İTS) should not be kept or used. ^[16]

In the US, the legal restrictions on pharmacies preparing copies of a licensed medicine (compounding) do not apply while the medicine is on the FDA’s shortage list. Tirzepatide entered this list on 15 December 2022 and was removed from the list on 2 October 2024. The FDA re-evaluated this decision and, with its decision dated 19 December 2024, confirmed that the shortage had ended and allowed a transition period for such production until 18 February 2025 (pharmacies) and 19 March 2025 (outsourcing facilities). In the same document the FDA stresses that compounded medicines have not undergone the FDA’s pre-approval review for safety, efficacy and quality. ^[12]

This guide does not address where or how the medicine can be obtained in any country.

Limits of this guide

This page summarizes what tirzepatide is, what evidence exists in which situations and what the official product information says; it does not recommend a personal dose or treatment. Doses in the trials are descriptions of trial conditions. All of the large trials mentioned here were funded by the manufacturer of the medicine. Data are limited on the risk of thyroid tumors in humans, use beyond 4 years and pregnancy outcomes. For people with diabetes, a history of thyroid cancer, pancreatitis or gallbladder disease, those planning to become pregnant and those using regular medication, tirzepatide is a medicine requiring physician assessment.