GLP-1 agonists

What is GLP-1 and how do GLP-1 agonists work?

GLP-1 is a hormone released after a meal from enteroendocrine cells in the gut. According to Drucker’s review, GLP-1 controls the post-meal rise in blood glucose by increasing insulin secretion and suppressing glucagon secretion; it also reduces gastric emptying and food intake. ^[1]

The same review describes how therapies targeting the GLP-1 receptor have developed toward orally available agonists and “multi-agonists” that stimulate more than one hormone receptor with a single molecule. ^[1] The first oral, non-peptide GLP-1 agonist, orforglipron, was licensed in the US on April 1, 2026; it is not licensed in Türkiye (Orforglipron). Tirzepatide (GIP and GLP-1) and retatrutide (GIP, GLP-1 and glucagon) are in this second group.

Which GLP-1 drugs exist? Comparison table

The Türkiye column is based on the TİTCK Licensed Human Medicinal Products List dated October 16, 2026; the years in parentheses are the first license dates in the list. In the list, GLP-1 receptor agonists appear under ATC A10BJ, their fixed combinations with insulin under A10AE, and tirzepatide separately under code A10BX16. The product containing lixisenatide alone is marked in the list as “Madde-23 gerekçeli askıda” (suspended, with justification). ^[2] The weekly exenatide formulation used in EXSCEL is not in the Türkiye list; the exenatide product in the list is a different formulation. ^[2]

Details of each drug are on its own page:

What is the effect of the class on the heart, kidney and death?

In a meta-analysis of eight large cardiovascular outcome trials in type 2 diabetes (60,080 patients), GLP-1 receptor agonists reduced major cardiovascular events by 14% (HR 0.86; 95% CI 0.80–0.93), all-cause death by 12% (HR 0.88), hospitalization for heart failure by 11% (HR 0.89) and the composite kidney outcome by 21% (HR 0.79). No increase was seen in severe hypoglycemia, retinopathy or pancreas-related adverse events. The effect did not differ significantly by the structural similarity of the molecules. ^[9]

This average result does not mean that every member has the same effect. In EXSCEL, weekly exenatide showed it was not worse than placebo but did not meet the superiority criterion (p=0.06). ^[3] In LEADER, liraglutide also reduced cardiovascular death (HR 0.78). ^[4] In REWIND, dulaglutide reduced the primary outcome but the difference in all-cause death was not significant (HR 0.90; 0.80–1.01). ^[5] All of these trials were conducted in people with type 2 diabetes; cardiovascular data in people without diabetes come from the SELECT trial described on the semaglutide page.

How does the effect on weight vary among members?

The size of weight loss varies markedly from molecule to molecule. In SURMOUNT-1, a 72-week trial in adults with obesity or overweight without diabetes, tirzepatide produced a mean weight loss of 15.0–20.9% depending on dose (placebo 3.1%). ^[7] In retatrutide’s 48-week phase 2 trial, the loss was 24.2% at the highest dose; however, this is a phase 2 trial of 338 people, and a dose-dependent increase in heart rate was also seen. ^[8] Percentages in different trials cannot be compared directly because participants and durations differ.

What are the shared side effects and warnings?

• Digestive: The most common side effects of the class are nausea, vomiting and diarrhea. In REWIND, a digestive side effect was reported in 47.4% of the dulaglutide group and 34.1% of the placebo group; in LEADER, the side effects most often leading to discontinuation of liraglutide were digestive. ^{[5] [4]} With tirzepatide and retatrutide as well, the most common side effects were digestive and were mostly seen during the dose-escalation period. ^{[7] [8]}
• Pancreas: In EXSCEL, the frequency of acute pancreatitis, pancreatic cancer and medullary thyroid cancer did not differ significantly from placebo; in LEADER, the frequency of pancreatitis was lower, not significantly, in the liraglutide group. ^{[3] [4]}
• Suicidal thoughts: In its April 2024 review covering dulaglutide, exenatide, liraglutide, lixisenatide and semaglutide, the EMA’s safety committee PRAC concluded that the available evidence does not support a causal relationship between these drugs and suicidal and self-harm thoughts and actions. ^[10]

The boxed warning on thyroid C-cell tumors, the contraindication in medullary thyroid cancer/MEN 2, restrictions in pregnancy and breastfeeding, and the aspiration warning in anesthesia are in each product’s own product information; they are transferred from the SmPC (Turkish KÜB) on the relevant drug pages. For NAION, the regulatory decision so far covers only semaglutide.

Reimbursement and counterfeit warning in Türkiye

In the SGK (Social Security Institution) EK-4/A List of Reimbursable Medicines published in the Official Gazette (Resmî Gazete) dated April 8, 2026, among products containing GLP-1 receptor agonists, only exenatide (Byetta) and the fixed combination of insulin glargine and lixisenatide (Soliqua) appear; products containing semaglutide, liraglutide, dulaglutide and tirzepatide are not in the list. ^[12]

In Türkiye, a letter from the Erzurum Provincial Health Directorate to the pharmacists’ chamber (chamber registration date May 20, 2026), referring to the TİTCK letter dated May 14, 2026, relays that reports of suspected counterfeiting of medicines containing GLP-1 receptor agonists have increased markedly; in pharmacy and pharmaceutical warehouse inspections, Ozempic, Saxenda and Wegovy pens and Mounjaro solution for injection are stated to carry a high counterfeit risk. The letter emphasizes that medicines should not be bought over the internet and that medicines that cannot be registered in the Medicine Track and Trace System (İTS) should not be kept or used. ^[13]

Unlicensed GLP-1 products: the retatrutide example

Retatrutide is not in the TİTCK list of licensed products. ^[2] The FDA has stated that retatrutide is not a component of an approved drug, has not been found safe and effective in any situation, and cannot be used in drugs prepared by pharmacies under US federal law. The FDA also reports that it has warned telehealth companies that market retatrutide to consumers and distributors that sell GLP-1 active ingredients to drug compounders. ^[11] The FDA has also issued an import alert to stop the entry into the country of GLP-1 active ingredients that may have been made without appropriate quality controls. ^[11] This guide does not address how to obtain any product.

Limits of this page

This page introduces GLP-1 receptor agonists as a class and summarizes a single notable trial for each member; it does not recommend choosing between drugs. The license status belongs to the TİTCK list of the stated date and may change. Which drug is suitable for whom depends on a physician’s assessment.