The approval of tirzepatide (Mounjaro) by the FDA is a significant advancement in treating type 2 diabetes. The mechanism of action, safety and efficiency of tirzepatide are penned down in this article. 

Key takeaways

1. The Food and Drug Administration (FDA) has authorised a revolutionary, first-of-its-kind medication for the treatment of type 2 diabetes. It is known as tirzepatide, a 'dual GIP/GLP-1 receptor agonist'.
2. It is administered as a once-weekly subcutaneous injection.
3. It has a dual impact, decreasing blood sugar and promoting weight reduction more effectively than existing medications for this illness.

Tirzepatide

Type 2 diabetes is a chronic, progressive disease that needs ongoing innovation to assist individuals in managing their blood glucose and weight. The Food and Drug Administration (FDA) has authorised tirzepatide (Mounjaro; Eli Lilly and Company), a new, dual-targeted therapy that has been demonstrated to enhance glycemic control in individuals with type 2 diabetes.

In adults with type 2 diabetes, the once-weekly glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist is advised as an addition to diet and exercise. Tirzepatide is a multifunctional peptide derived from the GIP peptide sequence, albeit it has been tweaked to bind to both GIP and GLP-1 receptors. With a half-life of roughly 5 days, once-weekly administration is feasible.

1. Data from clinical trials indicate that tirzepatide is more successful than other diabetes medications in lowering blood sugar levels.
2. The SURPASS studies revealed promising results for tirzepatide in a variety of patient categories.
3. The pharmaceuticals were evaluated as either stand-alone treatments or as additives to existing medications.

The mechanism behind it

Tirzepatide is the first medicine in a new class of diabetic treatments. It is an agonist for both the glucose-dependent insulinotropic polypeptide (GIP) and the GLP-1 receptor. GLP-1 and GIP are hormones called incretins that are released by the intestines after we eat. Incretins activate beta cells, which are insulin-producing cells in the pancreas, to secrete insulin. GLP-1 stimulates insulin secretion by the pancreas. Additionally, it decreases the amounts of glucagon, a hormone that keeps the blood sugar from falling too low.

Tizepatide counteracts this deficiency by activating the body's GLP-1 and GIP receptors.

Efficiency 

1. In the SURPASS-1 clinical study, researchers discovered that tirzepatide is useful for individuals with diabetes that is poorly managed by diet and exercise alone.
2. The subjects received one of three tirzepatide dosages: 5 milligrammes (mg), 10 milligrammes (mg), or 15 milligrammes (mg), or a placebo injection once weekly for forty weeks. Depending on the dose, the A1C decreased by a mean of 1.87 to 2.07 per cent. In addition, people receiving tirzepatide lost more weight than those in the placebo group: 7 to 9.5 kilogrammes (kg), or 15.4 to 20.9 pounds (lb).
3. In the SURPASS-2 clinical trials, the diabetic patients inadequately controlled with ≥1500 mg/day of metformin alone received the same doses of tirzepatide as in the previous study or 1 mg of injectible semaglutide once weekly for 40 weeks. Depending on the dose, tirzepatide lowered A1C by 2.01 to 2.3%, and semaglutide reduced it by 1.86%. The experiment also revealed that the tirzepatide group experienced considerably more weight loss than the semaglutide group. In the former, weight loss varied between 1.9 kg (4.2 lb) and 5.5 kg (11 lb) (12.1 lb).
4. The SURPASS-3 study compared tirzepatide to insulin degludec, an FDA-approved injectable diabetic medication. People with type 2 diabetes who had never used insulin and did not respond sufficiently to therapy with metformin alone or in combination with SGLT2 inhibitors were recruited for the trial. Participants receiving tirzepatide exhibited considerably more significant decreases in A1C than those receiving insulin degludec after 52 weeks. In addition, the first group lost much more weight.
5. Researchers recruited patients with T2DM with inadequately controlled oral antihyperglycemic medications with cardiovascular disease or high risk for cardiovascular events for the SURPASS-4 study. Participants got a 52-week course of tirzepatide or insulin glargine, two injectable diabetes medications. Again, people who used tirzepatide saw greater A1C reductions and weight loss than those who took insulin glargine.
6. The SURPASS-5 study assessed tirzepatide as an adjunctive medication for individuals with type 2 diabetes who were previously on insulin glargine with or without metformin. A1C and weight loss were assessed in subjects receiving a placebo or tirzepatide once a week in addition to their usual medication for forty weeks. Those receiving tirzepatide as an adjunctive therapy saw better A1C reductions and weight loss than those receiving a placebo.

Is it really safe?

1. Nausea, diarrhoea, vomiting, and constipation were the adverse effects of tirzepatide most often mentioned by trial participants. Infrequently, caused hypoglycemia in a few cases.
2. The nausea was most severe at the beginning of treatment and with increasing dosages and subsequently decreased with time.
3. The FDA reported that tirzepatide induces thyroid C-cell tumours in an experimental model, although it is uncertain if the medication causes similar tumours in people, including medullary thyroid cancer. According to the FDA, tirzepatide should not be administered to individuals having a personal or family history of medullary thyroid cancer or type 2 multiple endocrine neoplasia syndrome.
4. According to Eli Lilly, the medicine has not been evaluated in individuals with a history of pancreatitis and is not recommended for people with type 1 diabetes.

In a nutshell

The remarkable reduction in A1C to 5.7% is astounding. It will be interesting to see in future studies whether tirzepatide may help with cardiovascular disease, NASH [nonalcoholic fatty liver disease], and other consequences including retinopathy, nephropathy, and neuropathy.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising super specialist from New Delhi.